Fat tissue regeneration base material and bag-shaped fat tissue regeneration base material

Abstract

To provide a fat tissue regeneration base material that can retain its shape over a long duration until reconstruction of fat tissue and enables regeneration of fat tissue in a desired shape, and to provide a bag-shaped fat tissue regeneration base material using the fat tissue regeneration base material.SOLUTION: A fat tissue regeneration base material made of a bioabsorbable material, comprising a shell portion having an internal space and a plurality of openings on a surface that communicate with the internal space, and a column portion connecting opposing sites of the internal space of the shell portion.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a substrate for adipose tissue regeneration that can maintain its shape for a long period of time until adipose tissue is reconstructed and is capable of regenerating adipose tissue of a desired shape, and to a pouch-shaped substrate for adipose tissue regeneration that uses the substrate for adipose tissue regeneration. [Background technology]

[0002] When breast cancer treatment is difficult to cure with radiation therapy or chemotherapy alone, surgical removal (surgical therapy) is the method of choice. Traditionally, total mastectomy, in which the entire breast is removed along with the diseased tissue, was the most common treatment. However, in recent years, improvements in diagnostic technology have made it possible to detect the disease early and perform breast-conserving surgery, in which only the diseased part is removed while the lesion is still small. However, even with breast-conserving surgery, the resected area remains depressed, and the changes between before and after surgery still place a mental burden on patients. For this reason, an increasing number of patients are undergoing breast reconstruction surgery after surgical treatment to improve their quality of life.

[0003] Silicone implants are the most commonly used material for breast reconstruction surgery, but because they are non-resorbable, they remain in the body as foreign bodies. This can lead to implant deformation due to a foreign body reaction, resulting in pain, postoperative leakage due to implant breakage, and infection due to bacterial growth in the implant. There are also concerns about adverse effects such as allergies and cancer due to contact with the implant.

[0004] Another method is to harvest adipose tissue from a part of the body other than the breast and transplant it into the sunken area, but the adipose tissue is quickly absorbed into the body after transplantation, which can cause the sunken area to re-collapse.In addition, harvesting tissue creates a new wound, which is not necessarily desirable from the perspective of quality of life.

[0005] To solve these problems associated with conventional breast reconstruction surgery, the inventors have disclosed a breast reconstruction component in which a collagen-containing sponge is embedded within a hollow adipose tissue regeneration matrix made of polylactic acid (Patent Document 1). Patent Document 1 discloses that by filling the space created by partial mastectomy with the breast reconstruction component, surrounding cells invade the breast reconstruction component and use the breast reconstruction component as a scaffold for proliferation, thereby reconstructing the breast without transplanting adipose tissue from a site other than the breast. Furthermore, because the breast reconstruction component in Patent Document 1 is made of a bioabsorbable material, it is gradually absorbed into the body as breast regeneration progresses and eventually disappears, eliminating the need for removal like silicone implants and reducing the burden on the patient. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-140494 Summary of the Invention [Problem to be solved by the invention]

[0007] The breast reconstruction component in Patent Document 1 is highly effective as a breast reconstruction technique because it can regenerate the breast from the patient's own cells, but because the breast reconstruction component is exposed to external forces for a long period of time after transplantation until the fatty tissue regenerates, parts of the implanted breast reconstruction component can become crushed. When part of the breast reconstruction component is crushed, it becomes difficult for the tissue in the crushed part to regenerate, which can result in the breast not being regenerated as desired and can also result in a poor shape of the regenerated breast.

[0008] One possible solution to this problem is to increase the strength of the breast reconstruction component to prevent it from collapsing. However, simply increasing the hardness of the breast reconstruction component to increase its strength makes it less likely to collapse over the long term, but it also reduces its elasticity, creating a large difference in elasticity from the surrounding tissue. As a result, while the breast reconstruction component is able to regenerate fat tissue without collapsing, the shape of the regenerated tissue can deteriorate.

[0009] The present invention aims to provide a substrate for adipose tissue regeneration that can maintain its shape for a long period of time until adipose tissue is reconstructed and that is capable of regenerating adipose tissue of a desired shape, and a pouch-shaped substrate for adipose tissue regeneration that uses the substrate for adipose tissue regeneration. [Means for solving the problem]

[0010] The present invention includes the following Disclosures 1 to 9. The present invention will be described in detail below. [Disclosure 1] A substrate for adipose tissue regeneration made of a bioabsorbable material, the substrate having a shell portion having an internal space and a plurality of openings on the surface that lead to the internal space, and pillar portions that connect opposing parts of the internal space of the shell portion. [Disclosure 2] The substrate for adipose tissue regeneration according to Disclosure 1, wherein the pillar portion is a mesh cylindrical body. [Disclosure 3] The adipose tissue regeneration substrate according to Disclosure 1 or 2, wherein the pillar portion contains polylactic acid or a copolymer of lactic acid and another bioabsorbable material. [Disclosure 4] 4. The material for regenerating adipose tissue according to any one of Disclosures 1 to 3, wherein the shell is a spherical body containing polylactic acid or a copolymer of lactic acid and another bioabsorbable material. [Disclosure 5] 5. The substrate for adipose tissue regeneration according to any one of Disclosures 1 to 4, wherein the shell portion has a sponge-like porous body made of a bioabsorbable material inside. [Disclosure 6] 6. The material for regenerating adipose tissue according to any one of claims 1 to 5, wherein the compressive modulus of elasticity in the direction in which the pillars are connected is 0.1 kPa or more and 10 MPa or less. [Disclosure 7] A pouch-shaped substrate for adipose tissue regeneration comprising the substrate for adipose tissue regeneration according to any one of Disclosures 1 to 6, and a pouch-shaped body made of a bioabsorbable material having an opening and enclosing a plurality of the substrates for adipose tissue regeneration. [Disclosure 8] A pouch-shaped substrate for adipose tissue regeneration as described in Disclosure 7, wherein the bioabsorbable material constituting the pouch-shaped body includes polyglycolide, a copolymer of polyglycolide and other bioabsorbable materials, polylactic acid or a copolymer of lactic acid and other bioabsorbable materials. [Disclosure 9] 9. The pouch-shaped substrate for adipose tissue regeneration according to Disclosure 7 or 8, which is used by being implanted into a defect site caused by partial mastectomy.

[0011] The substrate for adipose tissue regeneration of the present invention is a substrate for adipose tissue regeneration made of a bioabsorbable material, and has a shell portion having an internal space and a plurality of openings on the surface that lead to the internal space, and a column portion connecting opposing parts of the internal space of the shell portion. Here, a schematic diagram showing an example of the substrate for adipose tissue regeneration of the present invention is shown in FIG. As shown in Figures 1(a) and 1(b), the adipose tissue regeneration substrate of the present invention has an internal space and a shell 1 with multiple openings on its surface that lead to the internal space, and a column 2 that connects opposing portions of the internal space of the shell 1, forming a closed shape as a whole. Only one column may be provided, or multiple columns may be provided depending on the size and shape of the adipose tissue regeneration substrate. In the adipose tissue regeneration substrate of the present invention, cells that pass through the openings in the shell 1 proliferate using the wall surface of the internal space as a scaffold, thereby regenerating adipose tissue. During this process, the column 2 supports the shell 1 from the inside, making it less likely to collapse, thereby preventing the adipose tissue regeneration substrate from collapsing for a sufficient period of time until adipose tissue regeneration occurs. Furthermore, by reinforcing the shell 1 with the column 2, the adipose tissue regeneration substrate of the present invention can be adjusted to an appropriate elasticity similar to that of the surrounding adipose tissue without excessively increasing the strength of the shell 1. Therefore, the regenerated adipose tissue can maintain a more desired shape than when a substrate for adipose tissue regeneration without a columnar portion is used. Furthermore, by using multiple substrates for adipose tissue regeneration of the present invention, it is possible to regenerate adipose tissue in the desired shape from a volume that would be difficult to regenerate using a single substrate for adipose tissue regeneration. Although not shown in the drawings for ease of viewing, the adipose tissue regeneration substrate of the present invention may have a sponge-like porous body made of a bioabsorbable material inside the shell. Providing a sponge-like porous body made of a bioabsorbable material inside the adipose tissue regeneration substrate increases the amount of cell scaffolding, thereby further promoting adipose tissue regeneration and increasing strength. The above-mentioned sponge-like porous body includes not only spongy shapes but also shapes with numerous voids, such as nonwoven fabrics and cotton.

[0012] The bioabsorbable materials constituting the shell and column are not particularly limited as long as they are conventionally used as implant materials. However, since adipose tissue regeneration takes approximately six months to a year, it is preferable for the materials to have the strength and decomposition rate to maintain the space in which the adipose tissue regeneration substrate is implanted during that period. Examples of such bioabsorbable materials include natural polymers such as collagen, gelatin, chitin, and chitosan, and synthetic polymers such as homopolymers of lactic acid, glycolic acid, ε-caprolactone, dioxanone, and trimethylene carbonate, as well as copolymers of at least two or more of these materials. Among these, polylactic acid or copolymers of lactic acid with other bioabsorbable materials are preferred due to their strength and in vivo decomposition rate suitable for adipose tissue regeneration substrates. Examples of copolymers of polylactic acid or lactic acid with other bioabsorbable materials include copolymers of lactide and glycolide, copolymers of lactic acid and glycolic acid, and copolymers of lactide and ε-caprolactone.

[0013] When the bioabsorbable material for the shell and spine is polylactide, a copolymer of lactide and glycolide, or a copolymer of lactide and ε-caprolactone, the weight-average molecular weight is preferably 4,000 to 300,000. By setting the weight-average molecular weight within this range, the decomposition rate can be made more suitable for the regeneration of adipose tissue. The weight-average molecular weight is more preferably 100,000 or more, and more preferably 200,000 or less.

[0014] The shape of the shell is not particularly limited as long as it can provide a scaffold for cell proliferation and maintain a space for the adipose tissue to be regenerated, and examples include spherical, columnar, irregular, etc. Among these, a spherical shape is preferred, and an ellipsoidal shape is more preferred, because it is less likely to lose its shape due to external forces after implantation, is less susceptible to physical irritation, and provides high cosmetic appearance after implantation in the body.

[0015] The size of the internal space of the shell is not particularly limited, but is preferably 10 mm 3 More than 400,000 mm 3By having the size of the internal space within the above range, it is possible to regenerate adipose tissue more reliably up to the center of the adipose tissue regeneration substrate while ensuring a space for regenerating adipose tissue. The size of the internal space is 25 mm or less. 3 More preferably, it is 50 mm or more. 3 More preferably, it is 200,000 mm or more. 3 It is more preferable that it is less than 100,000 mm 3 It is more preferable that:

[0016] The shape of the opening of the shell is not particularly limited, and may be circular, lattice-like, polygonal, irregular, or the like. The number of openings in the shell is also not particularly limited, as long as it is two or more. The size and occupancy of the openings in the shell are not particularly limited, as long as they allow cells to smoothly pass into the interior of the adipose tissue regeneration substrate. However, it is preferable that openings with a maximum length of 0.1 mm to 20 mm are distributed at an occupancy rate of 50% to 99% of the shell's surface area. An opening size and occupancy rate within this range can further improve the balance between the strength and cell infiltrability of the adipose tissue regeneration substrate. The maximum length of the openings is sufficient as long as they allow adipose tissue to penetrate while preventing the penetration of surrounding tissues other than fat that already exist as tissues. It is more preferable that the occupancy rate of the openings is 60% or more, more preferably 70% or more, of the shell's surface area to facilitate tissue infiltration. From the perspective of maintaining the shell's shape, it is more preferable that the occupancy rate be 95% or less, more preferably 90% or less. Note that, in this specification, the maximum length refers to the longest length measured when measuring the distance between two points on the openings.

[0017] More specific embodiments of the shell include mesh, porous capsule, etc. When the shell is made of mesh, the mesh constituting the shell may be a net, woven fabric, knitted fabric, etc. formed from monofilament or multifilament. Among these, mesh is more preferred from the viewpoints of elasticity, shape retention, adipose tissue penetration, etc.

[0018] When the shell is made of mesh, the thickness of the mesh filaments constituting the shell is not particularly limited, but is preferably 0.05 mm to 1 mm, more preferably 0.1 mm to 0.4 mm, from the viewpoints of mesh elasticity, shape retention, cell penetration, etc. The mesh size of the mesh constituting the shell is preferably in the range of 0.01 mm to 6 mm in both length and width, more preferably 0.02 mm to 5 mm.

[0019] The size of the shell (the size of the substrate for adipose tissue regeneration) is not particularly limited, but when the shell is spherical, it is preferable that the diameter of the shell is 5 mm or more and 100 mm or less. Having a shell size within this range makes it easier to adjust the shape when using multiple substrates for adipose tissue regeneration, and more reliably regenerates adipose tissue all the way to the center. The size of the shell is more preferably 8 mm or more in diameter, even more preferably 10 mm or more, more preferably 50 mm or less, and even more preferably 25 mm or less.

[0020] When the shell is ellipsoidal, the major axis of the shell is preferably 8 mm to 150 mm, more preferably 10 mm to 30 mm, and even more preferably 15 mm to 20 mm, and the minor axis of the shell is preferably 5 mm to 100 mm, more preferably 5 mm to 20 mm, and even more preferably 7 mm to 15 mm.

[0021] The shape of the pillar is not particularly limited as long as it can reinforce the shell while imparting appropriate elasticity, and examples thereof include a rod-like shape, a cylindrical shape, a spherical shape, etc. Among these, a cylindrical shape is preferred because it is less likely to hinder the penetration of adipose tissue.

[0022] More specific shapes of the pillar portion include block, mesh, porous, etc. Among these, mesh is preferred because it is less likely to hinder cell penetration and can impart appropriate elasticity to the adipose tissue regeneration substrate. That is, the pillar portion is preferably a mesh cylindrical body. Examples of the mesh include nets, woven fabrics, knitted fabrics, etc. formed from monofilaments or multifilaments.

[0023] When the pillar portion is made of mesh, the thickness of the mesh filaments making up the pillar portion is not particularly limited, but is preferably 0.05 mm to 1 mm, and more preferably 0.1 mm to 0.4 mm, from the viewpoints of mesh elasticity, shape retention, cell penetration, etc. The mesh size of the mesh making up the pillar portion is preferably in the range of 0.01 mm to 6 mm in both length and width, and more preferably in the range of 0.02 mm to 5 mm.

[0024] The position where the pillar portion is provided is not particularly limited as long as it is a position that connects opposing portions of the internal space of the shell portion. Specifically, when the shell portion has a prismatic shape, the pillars are preferably provided at positions passing through diagonals of the shell portion or at positions connecting opposing faces or opposing sides. When the shell portion has a spherical or ellipsoidal shape, the pillars are preferably provided on the meridians, major axis, or minor axis of the shell portion. In particular, when the shell portion has an ellipsoidal shape, the pillars are preferably provided on the minor axis of the shell portion.

[0025] The bioabsorbable material constituting the sponge-like porous body is not particularly limited, and examples thereof include synthetic polymers such as polyglycolide, polylactide, poly-ε-caprolactone, lactide-glycolide copolymer, glycolide-ε-caprolactone copolymer, lactide-ε-caprolactone copolymer, polycitric acid, polymalic acid, poly-α-cyanoacrylate, poly-β-hydroxy acid, polytrimethylene oxalate, polytetramethylene oxalate, polyorthoester, polyorthocarbonate, polyethylene carbonate, poly-γ-benzyl-L-glutamate, poly-γ-methyl-L-glutamate, poly-L-alanine, and polyglycol sebastic acid; natural polymers such as polysaccharides such as starch, alginic acid, hyaluronic acid, chitin, pectinic acid, and derivatives thereof; and proteins such as gelatin, collagen, albumin, and fibrin. Among these, collagen is preferred due to its high affinity with the living body.

[0026] When the sponge-like porous body contains collagen, it preferably contains 50% by weight or more of collagen, more preferably 60% by weight or more, even more preferably 70% by weight or more, even more preferably 80% by weight or more, particularly preferably 90% by weight or more, very preferably 95% by weight or more, and most preferably 100% by weight.

[0027] The collagen can be any collagen derived from the skin or tendons of cows, pigs, etc., without any particular limitations. Among them, from the viewpoint of eliminating antigenicity and increasing safety, atelocollagen is preferred, which is obtained by treating collagen with an enzyme such as protease or pepsin to remove as many telopeptides as possible.

[0028] Commercially available collagen-containing sponge-like porous bodies include, for example, Pernac (manufactured by Smith & Nephew Wound Management) and Terudermis (manufactured by Terumo Corporation).

[0029] The substrate for regenerating adipose tissue of the present invention preferably has a compressive modulus of elasticity of 0.1 kPa or more and 10 MPa or less in the direction in which the pillars are connected. By having the compressive elastic modulus within the above range when a load is applied in the direction in which the pillars of the adipose tissue regeneration substrate are connected (the extension direction of the pillars), the adipose tissue regeneration substrate has appropriate elasticity equivalent to that of the surrounding tissue, making it possible to regenerate adipose tissue with a more desired shape. The compressive elastic modulus is more preferably 0.5 kPa or more, and more preferably 100 kPa or less.

[0030] The method for producing the substrate for adipose tissue regeneration of the present invention is not particularly limited, and can be produced, for example, by wrapping a cylindrical pillar portion made of the above-mentioned sponge-like porous body and mesh in a mesh made of a bioabsorbable material and closing the ends. It is also possible to wrap the pillar portion in mesh and close the ends, and then insert the sponge-like porous body material through the opening. The method for closing the ends of the mesh is not particularly limited, and examples include tying filaments together and thermocompression bonding.

[0031] By using multiple substrates for adipose tissue regeneration of the present invention and enclosing them in a bag-shaped member with an opening, it is possible to regenerate a volume of adipose tissue that would be difficult to regenerate using only one substrate for adipose tissue regeneration of the present invention, and the shape of the regenerated tissue can be made more desirable. The present invention also includes a pouch-shaped adipose tissue regeneration substrate comprising the adipose tissue regeneration substrate of the present invention and a pouch-shaped body having an opening and made of a bioabsorbable material that encases a plurality of the adipose tissue regeneration substrates. Note that the term "basket-shaped" as used herein refers to a shape that has an internal space and prevents the adipose tissue regeneration substrates enclosed in the internal space from escaping to the outside.

[0032] The pouch-shaped substrate for adipose tissue regeneration of the present invention comprises the substrate for adipose tissue regeneration of the present invention and a pouch-shaped body made of a bioabsorbable material having an opening and enclosing a plurality of the substrates for adipose tissue regeneration. Here, a schematic diagram showing an example of the pouch-shaped substrate for adipose tissue regeneration of the present invention is shown in FIG. As shown in Figure 2, the pouch-shaped adipose tissue regeneration substrate of the present invention has a structure in which multiple adipose tissue regeneration substrates, each having a shell 1 and a column 2, are enclosed inside a pouch-like body 3. The pouch-like body 3 has many openings and an internal space, and is closed so that the adipose tissue regeneration substrates enclosed in the internal space do not leak out. The pouch-shaped adipose tissue regeneration substrate of the present invention has multiple adipose tissue regeneration substrates bundled together in a pouch-like body, making it easy to implant in large spaces and highly easy to handle. Furthermore, since multiple adipose tissue regeneration substrates are wrapped in the pouch-like body 3, the adipose tissue regeneration substrates do not scatter over a wide area, making it possible to implant them in a shape close to the shape after regeneration. Furthermore, even if an external force is applied after implantation, the adipose tissue regeneration substrate does not move outside the pouch-like body 3, making it less likely to lose its shape at the time of implantation, and allowing adipose tissue to be regenerated in the desired shape.

[0033] The shape of the bag-like body is not particularly limited, and any shape can be used depending on the ease of shaping at the implantation site, such as a rectangular bag-like shape, a circular bag-like shape, etc. Specific embodiments include a bag-like body made of a mesh woven from filaments, a porous bag-like body, etc.

[0034] The bioabsorbable material constituting the bag-shaped body is not particularly limited, and since it does not need to maintain its strength for a long period of time compared to the enclosed adipose tissue regeneration substrate, it can be made of the same bioabsorbable material as the sponge-like porous body. However, it must be strong enough to hold multiple adipose tissue regeneration substrates and maintain their overall shape. Since it will be implanted in the body as an implant, it is preferable that it induce as little inflammatory or foreign body reaction as possible. Such bioabsorbable materials include materials that can be used as sutures, and polyglycolide, polylactic acid, polycaprolactone, polydioxane, trimethylene carbonate, or copolymers thereof are preferred. Polyglycolide, copolymers of polyglycolide and other bioabsorbable materials, and copolymers of polylactic acid or lactic acid and other bioabsorbable materials are more preferred.

[0035] When the bag-shaped body is made of a mesh of woven filaments, the thickness of the filaments constituting the bag-shaped body is not particularly limited, but from the viewpoint of the balance between flexibility and strength, it is preferably 0.01 mm or more, more preferably 0.1 mm or more, and is preferably 2 mm or less, more preferably 0.5 mm or less.

[0036] The occupancy rate of the opening of the bag-shaped body is not particularly limited as long as it allows cells to pass smoothly through the substrate for adipose tissue regeneration, but it is preferably 50% or more and 99% or less of the surface area of ​​the bag-shaped body. An occupancy rate of the opening in this range can further improve the balance between the strength of the bag-shaped body and the invadibility of cells. The occupancy rate of the opening of the bag-shaped body is more preferably 60% or more of the surface area of ​​the bag-shaped body, even more preferably 70% or more, more preferably 95% or less, and even more preferably 90% or less.

[0037] The size of the opening of the above-mentioned pouch-shaped body is not particularly limited as long as it does not inhibit the entry of cells into the adipose tissue regeneration substrate and the adipose tissue regeneration substrate does not protrude outside the pouch-shaped body, but when the shape of the adipose tissue regeneration substrate is spherical or ellipsoidal, the maximum length of the opening of the pouch-shaped body is preferably 1 / 50 or more times the diameter or minor axis of the adipose tissue regeneration substrate, more preferably 1 / 20 or more times, preferably 1 / 3 or less, and more preferably 1 / 10 or less times. By setting the size of the opening of the pouch-shaped body within the above range, the shapeability and operability of the entire pouch-shaped adipose tissue regeneration substrate can be further improved.

[0038] When the bag-shaped body is made of a mesh, the specific numerical value of the mesh size of the bag-shaped body is determined appropriately depending on the size of the substrate for adipose tissue regeneration, but for example, it is preferable that both the length and width are 0.02 mm or more and 2 mm or less, and more preferably 0.05 mm or more and 1 mm or less.

[0039] The size of the bag-shaped body can be adjusted appropriately depending on the volume of the implantation site and the number of adipose tissue regeneration substrates to be enclosed, but from the viewpoint of increasing the moldability of the bag-shaped adipose tissue regeneration substrate while suppressing collapse of the bag-shaped adipose tissue regeneration substrate after implantation, the internal space of the bag-shaped body is preferably 1.2 times or more, more preferably 1.5 times or more, and preferably 3 times or less, and more preferably 2 times or less of the total volume of the adipose tissue regeneration substrate. Note that the total volume of the adipose tissue regeneration substrate also includes the volume of the internal space of the adipose tissue regeneration substrate.

[0040] The number of adipose tissue regeneration substrates in the pouch-shaped adipose tissue regeneration substrate of the present invention is not particularly limited as long as it is two or more, and can be adjusted appropriately depending on the size of the pouch-shaped body and the size of the space in which it is to be implanted. However, from the viewpoint of ease of handling and further promoting the regeneration of adipose tissue, it is preferably five or more, more preferably ten or more, and preferably 100 or less, and more preferably 50 or less.

[0041] The method for producing the pouch-shaped adipose tissue regeneration substrate of the present invention is not particularly limited, and for example, the substrate can be produced by producing multiple adipose tissue regeneration substrates using the method described above, wrapping the resulting adipose tissue regeneration substrates in a mesh pouch made of a bioabsorbable material, and closing the ends. The method for closing the ends of the pouch is not particularly limited, and examples include tying filaments together and thermocompression bonding.

[0042] The adipose tissue regeneration substrate and pouch-shaped adipose tissue regeneration substrate of the present invention are used for the purpose of implanting them into adipose tissue to regenerate the adipose tissue. Use of the present invention makes it possible to regenerate living adipose tissue composed of one's own cells without the need to excise and implant tissue from another site. Examples of adipose tissue for which the present invention can be used include the breast, buttocks, and abdomen. In particular, the pouch-shaped adipose tissue regeneration substrate of the present invention can maintain its shape while retaining elasticity similar to that of the surrounding tissue for a long period of time until the adipose tissue is regenerated, and can regenerate the adipose tissue in the desired shape, making it highly effective for the purpose of breast regeneration when implanted into a defect created by partial mastectomy. [Effects of the Invention]

[0043] According to the present invention, it is possible to provide a substrate for adipose tissue regeneration that can maintain its shape for a long period of time until adipose tissue is reconstructed and that is capable of regenerating adipose tissue of a desired shape, and a pouch-shaped substrate for adipose tissue regeneration that uses the substrate for adipose tissue regeneration. [Brief explanation of the drawings]

[0044] [Figure 1] FIG. 1 is a schematic diagram showing an example of the substrate for adipose tissue regeneration of the present invention. [Figure 2] FIG. 1 is a schematic diagram showing an example of a pouch-shaped substrate for adipose tissue regeneration according to the present invention. [Figure 3] 1 is a graph showing the results of evaluation of strength retention. [Figure 4] 1 shows a hematoxylin-eosin stained image of the implanted area 6 months after implanting the adipose tissue regeneration scaffold obtained in Example 1 into the groin of a rat. [Figure 5] 1 shows a hematoxylin-eosin stained image of the implanted area 12 months after implanting the adipose tissue regeneration scaffold obtained in Example 1 into the groin of a rat. [Figure 6] 1 shows a hematoxylin-eosin stained image of the implanted area 6 months after implanting the adipose tissue regeneration substrate obtained in Comparative Example 1 into the groin area of ​​a rat. [Figure 7] 1 shows a hematoxylin-eosin stained image of the implanted area 12 months after implanting the adipose tissue regeneration substrate obtained in Comparative Example 1 into the groin area of ​​a rat. [Figure 8] 8 is a graph showing the total tissue area within the adipose tissue regeneration scaffold in FIGS. 4 to 7. [Figure 9] 8 is a graph showing the area of ​​adipose tissue within the adipose tissue regeneration substrate in FIGS. DETAILED DESCRIPTION OF THE INVENTION

[0045] The following examples will explain the present invention in more detail, but the present invention is not limited to these examples.

[0046] Example 1 (1) Manufacturing of adipose tissue regeneration substrates and pouch-shaped adipose tissue regeneration substrates A mesh sheet (filament thickness: 0.2-0.3 mm, mesh opening: 0.5 x 0.5 mm to 1 x 1 mm) made of polylactic acid (weight-average molecular weight: 220,000) monofilament was fabricated and cut into a 5 mm diameter cylindrical shape to obtain a pillar. A mesh sheet (filament thickness: 0.2-0.3 mm, mesh opening: 1 x 1 mm to 2 x 2 mm) made of polylactic acid (weight-average molecular weight: 220,000) monofilament was then wrapped around the pillar, with the pillar positioned at the center and on the minor axis. The ends were then sealed by thermocompression to obtain a substrate for adipose tissue regeneration, consisting of a pillar and an oval-shaped shell with a major axis of 18 mm and a minor axis of 7.5 mm. Next, 30 of the obtained adipose tissue regeneration substrates were wrapped in an envelope-shaped bag made of polyglycolide multifilament (filament configuration: 0.015 mm x 12, mesh size: 0.05 mm x 0.05 mm), and the ends were heat-sealed to obtain a bag-shaped adipose tissue regeneration substrate with an internal space of approximately 30 cc, containing 30 adipose tissue regeneration substrates.

[0047] (2) Compression ratio measurement The resulting adipose tissue regeneration substrate was placed in the center of the specimen stage of a compression testing device (AG-X plus, manufactured by Shimadzu Corporation) and subjected to a compression strength test to measure the compression ratio. The applied load was twice the 3.2 kPa load that can be applied in vivo, and the compression test conditions were a speed of 10 mm / min. The measurement result showed a compression ratio of 9.86%.

[0048] (3) Evaluation of compressive elastic modulus The resulting adipose tissue regeneration substrate was placed in the center of the specimen stage of a compression testing device (AG-X plus, manufactured by Shimadzu Corporation) and subjected to a compressive strength test to measure the compressive modulus when a load was applied in the direction of the connection of the column of the adipose tissue regeneration substrate (the extension direction of the column). The compressive modulus was calculated by dividing the difference in compressive stress (σ2 - σ1) by the difference in compressive strain ((d2 - d1) / minor axis), where σ1 and σ2 are the compressive stresses corresponding to two compression displacements of d1 = 0.30 mm and d2 = 0.40 mm, respectively. The compression test was performed at a speed of 10 mm / min. The measured compressive modulus was 43.4 kPa.

[0049] (Comparative Example 1) Except for forming only a shell without providing a pillar portion, a substrate for adipose tissue regeneration and a pouch-shaped substrate for adipose tissue regeneration were obtained in the same manner as in Example 1. Furthermore, the compression ratio and compressive modulus of the obtained substrate for adipose tissue regeneration were measured in the same manner as in Example 1, and the compression ratio was 14.04% and the compressive modulus was 16.1 kPa. The compressive modulus was measured by applying a load in the minor axis direction of the substrate for adipose tissue regeneration.

[0050] <Evaluation> The adipose tissue regeneration materials obtained in the Examples and Comparative Examples were evaluated as follows.

[0051] (Evaluation of strength retention) The obtained adipose tissue regeneration substrate was immersed in 10x concentrated phosphate buffer solution (PBS) and allowed to stand at 80°C. The compression ratio of the adipose tissue regeneration substrate was measured using the same method as described above after 0 days (before immersion in PBS), 2 days (equivalent to 9 months elapsed in the body), 2.5 days (equivalent to 12 months elapsed in the body), and 3 days (equivalent to 15 months elapsed in the body). The results are shown in Figure 3.

[0052] (Evaluation of tissue regeneration) The obtained adipose tissue regeneration substrates were implanted into the left and right groin of eight rats (F344) that had been completely analgesic and sedated with isoflurane inhalation anesthesia, one each. That is, a total of eight adipose tissue regeneration substrates obtained in Example 1 and a total of eight adipose tissue regeneration substrates obtained in Comparative Example 1 were implanted into the groin of the rats. The rats were divided into two groups, Group 1 and 2, and the rats in Group 1 were euthanized 6 months after substrate implantation, and the rats in Group 2 were euthanized 12 months after substrate implantation, and tissues were collected from the implantation sites. Each collected tissue was fixed in 10% formalin solution and then embedded in paraffin to prepare tissue blocks. For each block, three cross-sectional sections, including the base material, were prepared, and each section was HE stained. Based on the microscopic images of each stained section taken with a fluorescence microscope (BZ-X810, manufactured by KEYENCE), the cross-sectional area (mm ) of the internal space of the base material was calculated. 2 ), and the cross-sectional area of ​​the adipose tissue generated in the internal space (mm 2 ) were identified. The results are shown in Figures 8 and 9. The cross-sectional area of ​​the internal space was defined as the area enclosed by the closed curve connecting the cross-sectional centers of the wires of the substrate, as identified in the microscopic image. The cross-sectional area of ​​the adipose tissue was defined as the area enclosed by the outline of the collection of adipocytes, as identified in the microscopic image. ImageJ was used as image processing software for calculating the area.

[0053] Figures 4 and 5 show hematoxylin-eosin stained images of the implanted area 6 and 12 months after implantation of the adipose tissue regeneration material obtained in Example 1 into the groin of a rat, and Figures 6 and 7 show hematoxylin-eosin stained images of the implanted area 6 and 12 months after implantation of the adipose tissue regeneration material obtained in Comparative Example 1 into the groin of a rat. In addition, Figure 8 shows a graph representing the total tissue area within the adipose tissue regeneration material in Figures 4 to 7 (the area surrounded by the black dashed line in Figures 4 to 7), and Figure 9 shows a graph representing the adipose tissue area within the adipose tissue regeneration material in Figures 4 to 7 (the area surrounded by the white dashed line in Figures 4 to 7). 4 to 7, it can be seen that, due to the presence of a pillar, the shell is less likely to collapse even 12 months after transplantation, reducing the decrease in total tissue area and promoting the regeneration of adipose tissue in Example 1. On the other hand, in Comparative Example 1, which does not have a pillar, many shells collapsed 12 months after transplantation, significantly reducing the total tissue area and also reducing the regeneration of adipose tissue (area of ​​adipose tissue). [Industrial Applicability]

[0054] According to the present invention, it is possible to provide a substrate for adipose tissue regeneration that can maintain its shape for a long period of time until adipose tissue is reconstructed and that is capable of regenerating adipose tissue of a desired shape, and a pouch-shaped substrate for adipose tissue regeneration that uses the substrate for adipose tissue regeneration. [Explanation of symbols]

[0055] 1 Shell 2 Pillar part 3 Bag-like body

Claims

1. A substrate for adipose tissue regeneration made of a bioabsorbable material, A substrate for adipose tissue regeneration comprising a shell having an internal space and a plurality of openings on the surface that lead to the internal space, and a column connecting opposing parts of the internal space of the shell.

2. The substrate for adipose tissue regeneration according to claim 1, wherein the column portion is a mesh cylindrical body.

3. 3. The substrate for adipose tissue regeneration according to claim 1, wherein the pillar portion comprises polylactic acid or a copolymer of lactic acid and another bioabsorbable material.

4. 3. The substrate for adipose tissue regeneration according to claim 1, wherein the shell is a spherical body containing polylactic acid or a copolymer of lactic acid and another bioabsorbable material.

5. 3. The substrate for adipose tissue regeneration according to claim 1, wherein the shell portion has a sponge-like porous body made of a bioabsorbable material inside.

6. 3. The substrate for regenerating adipose tissue according to claim 1, wherein the compressive modulus in the direction in which the columnar portions are connected is 0.1 kPa or more and 10 MPa or less.

7. A bag-shaped adipose tissue regeneration substrate comprising the adipose tissue regeneration substrate according to claim 1 or 2, and a bag-shaped body made of a bioabsorbable material having openings and enclosing a plurality of said adipose tissue regeneration substrates.

8. 8. The pouch-shaped substrate for adipose tissue regeneration according to claim 7, wherein the bioabsorbable material constituting the pouch-shaped body includes polyglycolide, a copolymer of polyglycolide and another bioabsorbable material, polylactic acid, or a copolymer of lactic acid and another bioabsorbable material.

9. The pouch-shaped substrate for adipose tissue regeneration according to claim 7, which is used by being implanted in a defect site caused by partial mastectomy.

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