Bone growth structure

Abstract

This bone augmentation structure comprises a collagen tube and a collagen structure stored within the collagen tube. The collagen tube has a porosity of 70-98%.

Description

Technical Field

[0001] The present invention relates to a structure for bone growth. This application claims priority based on Japanese Patent Application No. 2020-074322 filed in Japan on April 17, 2020, and incorporates the content herein by reference.

Background Art

[0002] Implant treatment is a type of prosthetic treatment method and has come to be used in many clinical settings. The advantages of implant treatment include improved occlusal force, the absence of the need for treatment of adjacent teeth, the ability to perform fixed prosthetic treatment instead of removable dentures, and improved maintenance and stability of dentures. On the other hand, implant treatment requires sufficient bone mass for implant body implantation and is greatly affected by bone mass and bone quality.

[0003] When alveolar bone is lost due to periodontal disease or the like, it is necessary to perform autotransplantation in which bone is harvested from the jawbone or the like and transplanted, or to construct bone at the implant implantation site using artificial bone such as β-TCP. Autotransplantation has high osteoinductive ability and low antigenicity, but since bone is harvested, it has a large surgical invasiveness to the patient and the scope of application is limited. Artificial bone tends to be slightly inferior in infection resistance compared to autotransplantation. In addition, since artificial bone is often granular, it has poor formability and requires the combined use of a membrane or the like. Furthermore, both autotransplantation and artificial bone require time to sufficiently increase bone mass, and there are cases where sufficient bone mass cannot be increased even over time.

[0004] Collagen is one of the most widely used biomaterials as a cell carrier in tissue engineering. For example, Patent Document 1 describes the use of an oriented collagen gel for tissue regeneration.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] In medical technologies that require bone mass such as implant treatment, a method for growing bone that can simply and stably grow bone is needed.

[0007] Therefore, an object of the present invention is to provide a bone growth structure that can simply and stably grow bone.

MEANS FOR SOLVING THE PROBLEMS

[0008] The present invention includes the following aspects. [1] A bone growth structure including a collagen tube and a collagen structure housed in the collagen tube, wherein the porosity in the collagen tube is 70 to 98%. [2] The bone growth structure according to [1], wherein the collagen tube has orientation in the axial direction of the collagen tube. [3] The bone growth structure according to [2], wherein the collagen structure has orientation, and the collagen structure is housed in the collagen tube such that the direction of the orientation of the collagen structure coincides with the direction of the orientation of the collagen tube. [4] The bone growth structure according to [3], wherein the collagen structure includes a plurality of collagen strings having orientation in the axial direction, and the direction of the orientation of the plurality of collagen strings coincides with the direction of the orientation of the collagen tube. [5] The bone growth structure according to [4], wherein in the collagen structure, the plurality of collagen strings are arranged such that the distance between the centers of adjacent collagen strings is 100 to 400 μm. [6] The bone growth structure according to any one of [1] to [5], wherein the collagen structure is a sheet-shaped collagen structure. [7] The bone growth structure according to [6], wherein the sheet-shaped collagen structure forms a wound body and is accommodated in the collagen tube. [8] The bone growth structure according to any one of [1] to [5], wherein the collagen structure is a tube-shaped collagen structure. [9] The bone growth structure according to [8], wherein a plurality of the tube-shaped collagen structures are accommodated in the collagen tube.

[10] The bone growth structure according to [9], wherein the plurality of tube-shaped collagen structures are composed of two or more types of tube-shaped collagen structures having different outer diameters.

[11] The bone growth structure according to any one of [1] to [9], which is a dental material.

[12] The bone growth structure according to

[10] , which is for alveolar bone growth.

Advantages of the Invention

[0009] According to the present invention, there is provided a bone growth structure capable of simply and stably growing bone.

Brief Description of the Drawings

[0010]

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Mode for Carrying Out the Invention

[0011] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings as appropriate. In the drawings, the same or corresponding parts are denoted by the same or corresponding reference numerals, and duplicate explanations are omitted. The dimensional ratios in each figure are exaggerated for the purpose of explanation and do not necessarily match the actual dimensional ratios.

[0012] Unless otherwise specified, the lengths, widths, distances, etc. of bone growth structures, collagen sheets, collagen tubes, collagen strings, etc. refer to those when these collagen structures are in a dry state.

[0013] The "collagen structure" means a structure composed of collagen. The shape of the collagen structure is not particularly limited. A collagen tube is a collagen structure in the shape of a tube. The tube shape refers to a hollow cylindrical shape with both ends of the cylinder open. The axial length of the tube shape is not particularly limited. The sizes of the outer diameter and inner diameter of the tube shape are not particularly limited. A collagen sheet is a collagen structure in the shape of a sheet. The sheet shape refers to a flat plate shape. The two-dimensional shape of the sheet shape is not particularly limited. The sheet shape may have irregularities on its surface.

[0014] [Bone growth structure] In one embodiment, the present invention provides a bone growth structure. The bone growth structure of this embodiment includes a collagen tube and a collagen structure accommodated in the collagen tube. The porosity in the collagen tube is 70 - 98%.

[0015] ≪First Embodiment≫ A configuration example of the bone growth structure of the first embodiment will be described with reference to FIGS. 1 and 2. In the bone growth structure 100 shown in FIG. 1, a wound body 11 of a collagen sheet 10 is accommodated in a collagen tube 20. The collagen sheet 10 is a collagen structure in the shape of a sheet. As shown in FIG. 2, the collagen sheet 10 includes a plurality of collagen strings 1. The wound body 11 of the collagen sheet 10 is accommodated in the collagen tube 20 such that the orientation direction of the collagen strings 1 coincides with the orientation direction of the collagen tube 20. FIG. 3 shows a photograph of a specific example of the bone growth structure. A total of 12 bone growth structures are shown in the photograph of FIG. 3.

[0016] Collagen is a type of protein and is contained in all tissues in the body such as skin, muscles, internal organs, and bones. Different from other proteins, collagen exists in the gaps between cells, that is, outside the cells. Collagen forms structures such as fibers and membranes outside the cells. Most of the collagen exists in a state where it is insoluble in water. It is considered that collagen plays a role like glue that attaches cells to each other in the living body and also plays a role like a partition that arranges cells in the correct positions. Collagen is a type of cell matrix.

[0017] The collagen used in the bone growth structure of this embodiment is not particularly limited. Collagen may be derived from any biological species and tissue. For example, those extracted from animals such as rat tails, pig skins, cow hides, ostriches, and fish can be used. For example, collagen obtained from the skin, bones, cartilage, tendons, or other organs of mammals (such as cows, pigs, horses, rabbits, mice, etc.) or birds (such as chickens, etc.) may also be used. Further, collagen-like proteins obtained from the skin, bones, cartilage, fins, scales, or other organs of fish (such as cod, flounder, sole, salmon, trout, tuna, mackerel, sardines, sea bream, herring, sharks, etc.) may also be used. The method for extracting collagen is not particularly limited, and those extracted by known extraction methods can be used without particular limitation. Collagen may be obtained by genetic recombination technology. Further, atelocollagen treated with enzymes to suppress antigenicity may be used. Also, unmodified soluble collagen such as acid-soluble collagen, salt-soluble collagen, or enzyme-solubilized collagen (atelocollagen); chemically modified collagen such as acylation (succinylation, phthalation, etc.), esterification (methylation, etc.), or deamidation by alkali solubilization; and insoluble collagen such as tendon collagen may be used.

[0018] (Collagen tube) A collagen tube is a tube composed of collagen. As the collagen tube shown as the collagen tube 20 in Fig. 1, one having axial orientation can be used. The axial direction of the collagen tube means the stretching direction of the tube. That the collagen structure has orientation means that the running directions of the collagen fibers constituting the collagen structure are aligned in a predetermined direction. That is, the collagen tube having axial orientation is a collagen tube in which the running directions of the collagen fibers constituting the collagen tube are aligned in the axial direction.

[0019] The collagen tube having axial orientation can be produced by a known method. For example, the methods described in Japanese Patent No. 5669760, Japanese Unexamined Patent Application Publication No. 2016-154866, etc. can be used. For example, by giving a flow in a certain direction during the process of gelling a collagen solution, a string-like (cord-like) collagen gel having axial orientation is formed. Next, after aligning the orientation of the string-like collagen gel and arranging it in a sheet shape, it is formed into a tube shape using a mandrel or the like to produce a collagen gel tube. At this time, the orientation of the string-like collagen gel is made to be the axial direction of the tube. By drying the collagen gel tube, a collagen tube having axial orientation can be obtained. In addition to the above method, as a method for imparting orientation to the collagen structure, for example, a method of applying a strong magnetic field during the process of forming a string-like collagen gel, a method of spin-coating the collagen gel, a method of mechanically (physically) stretching the collagen gel in a certain direction, etc. can be mentioned, but it is not limited thereto.

[0020] The collagen tube may be composed of a single layer or a plurality of layers. The collagen tube of a plurality of layers can be produced by laminating a plurality of sheet-shaped collagen gels formed to have orientation so that the directions of their orientations coincide, forming them into a tube shape using a mandrel or the like, and drying.

[0021] Commercially available collagen tubes may be used. Examples of commercially available collagen tubes include, for example, the oriented collagen seamless tube and the composite oriented collagen seamless tube manufactured by Atorie Co., Ltd.

[0022] The size of the collagen tube is not particularly limited, and an appropriate size can be selected according to the application. The length L of the collagen tube 20 can be, for example, 1 to 30 mm. The length L of the collagen tube 20 is preferably, for example, 2 to 20 mm, more preferably 3 to 15 mm, even more preferably 4 to 10 mm, and particularly preferably 4 to 8 mm. When the length L of the collagen tube 20 is within the above preferred range, the shape of the bone growth structure is likely to be maintained.

[0023] The inner diameter ID of the collagen tube 20 can be, for example, 0.5 to 20 mm. The inner diameter ID of the collagen tube 20 is preferably, for example, 1 to 15 mm, more preferably 2 to 10 mm, even more preferably 3 to 8 mm, and particularly preferably 3 to 5 mm. When the inner diameter ID of the collagen tube 20 is within the above preferred range, the shape of the bone growth structure is likely to be maintained, and the porosity inside the collagen tube is likely to be maintained.

[0024] The thickness T of the collagen tube 20 can be, for example, 5 to 200 μm. The thickness T of the collagen tube 20 is preferably, for example, 20 to 100 μm, more preferably 30 to 80 μm, even more preferably 30 to 60 μm, and particularly preferably 30 to 50 μm. When the thickness T of the collagen tube 20 is within the above preferred range, the shape of the bone growth structure is likely to be maintained, and when transplanted into the living body, cells are likely to be incorporated into the bone growth structure.

[0025] The outer diameter OD of the collagen tube 20For example, it can be 0.6 to 20 mm. The outer diameter OD of the collagen tube 20 For example, 1 to 15 mm is preferable, 2 to 10 mm is more preferable, 3 to 8 mm is even more preferable, and 3 to 5 mm is particularly preferable. The outer diameter OD of the collagen tube 20 is the inner diameter ID 20 and the thickness T 20 are defined by

[0026] (Collagen sheet) The collagen sheet is a sheet made of collagen. The collagen sheet may include a plurality of collagen strings having orientation in the axial direction. For example, the collagen sheet 10 shown in FIG. 2 has a structure in which a plurality of collagen strings 1 are arranged substantially parallel to each other on the surface of the collagen substrate 2.

[0027] <Collagen string> The collagen string is a string-shaped (cord-shaped) collagen structure. A collagen string having orientation in the axial direction can be used. The axial direction of the collagen string means the stretching direction of the string. A collagen string having orientation in the axial direction is a collagen string in which the traveling directions of the collagen fibers constituting the collagen string are aligned in the axial direction.

[0028] The collagen string having orientation in the axial direction can be produced by a known method. For example, similar to the above-mentioned collagen tube having orientation in the axial direction, the methods described in Japanese Patent No. 5669760 and Japanese Unexamined Patent Application Publication No. 2016-154866 can be used. For example, by drying the string-shaped collagen gel described in the method for producing the above-mentioned collagen tube having orientation, a collagen string having orientation in the axial direction can be obtained.

[0029] Commercially available collagen strings may be used. Examples of commercially available collagen strings include, for example, the oriented collagen strings manufactured by Atorie Co., Ltd.

[0030] The size of the collagen string is not particularly limited, and an appropriate size can be selected according to the application. The length L1 of the collagen string can be, for example, 1 to 30 mm. The length L1 of the collagen string is preferably, for example, 2 to 20 mm, more preferably 3 to 15 mm, still more preferably 4 to 10 mm, and particularly preferably 4 to 8 mm. When the length L1 of the collagen string is within the above-preferred range, the shape of the bone growth structure is likely to be maintained. The length L1 of the collagen string may be longer or shorter than the length L 20 of the collagen tube, but it is preferably substantially the same length as the length L 20 of the collagen tube. The length L1 of the collagen string is preferably selected according to the length L2 of the collagen matrix described later. By matching the length L1 of the collagen string with the length L2 of the collagen matrix, when transplanted into the living body, the outflow of collagen fibers is suppressed, and cells are more likely to be taken into the bone growth structure.

[0031] The diameter D1 of the collagen string can be, for example, 10 to 500 μm. The diameter D1 of the collagen tube is preferably, for example, 20 to 300 μm, more preferably 30 to 200 μm, still more preferably 40 to 100 μm, and particularly preferably 45 to 60 μm. When the diameter D1 of the collagen string is within the above-preferred range, the shape of the bone growth structure is likely to be maintained, and the porosity within the collagen tube is likely to be maintained.

[0032] <Collagen matrix> The collagen matrix is a flat collagen structure. The collagen matrix may or may not have orientation. The shape of the collagen matrix is not particularly limited as long as it is flat. Examples of the two-dimensional shape of the collagen matrix include, but are not limited to, polygonal shapes (rectangular shape, square shape, parallelogram shape, trapezoidal shape, etc.), circular shape, elliptical shape, etc. As the two-dimensional shape of the collagen matrix, a rectangular shape or a square shape is preferable, and a rectangular shape is more preferable.

[0033] The collagen matrix 2 shown in FIG. 2 has a rectangular shape. When the collagen matrix is rectangular, the length L2 of the collagen matrix can be, for example, 1 to 30 mm. The length L2 of the collagen matrix is preferably, for example, 2 to 20 mm, more preferably 3 to 15 mm, still more preferably 4 to 10 mm, and particularly preferably 4 to 8 mm. When the length L2 of the collagen matrix is within the above preferable range, the shape of the bone growth structure is easily maintained. The length L2 of the collagen matrix may be longer or shorter than the length L 20 of the collagen tube, but it is preferably substantially equal to the length L 20 of the collagen tube. By matching the length L2 of the collagen matrix to the length L 20 of the collagen tube, the shape of the bone growth structure is easily maintained. In addition, when transplanted into the living body, the outflow of collagen fibers is suppressed, and cells are easily incorporated into the bone growth structure.

[0034] When the collagen matrix is rectangular, the width W2 of the collagen matrix can be appropriately selected according to the inner diameter of the collagen tube. The width W2 of the collagen matrix is set so that the porosity in the collagen tube can be 70 to 98%. The width W2 of the collagen matrix can be, for example, 1 to 100 mm. The width W2 of the collagen matrix is preferably, for example, 5 to 80 mm, more preferably 10 to 70 mm, still more preferably 15 to 60 mm, and particularly preferably 20 to 50 mm. When the width W2 of the collagen matrix is within the above preferable range, the porosity in the collagen tube is easily maintained.

[0035] Although the thickness T2 of the collagen substrate is not particularly limited, for example, it can be 5 to 200 μm. The thickness T2 of the collagen substrate is preferably, for example, 20 to 100 μm, more preferably 30 to 80 μm, still more preferably 30 to 60 μm, and particularly preferably 30 to 50 μm. When the thickness T2 of the collagen substrate is within the above-mentioned preferred range, the shape of the bone growth structure is likely to be maintained, and the porosity within the collagen tube is likely to be maintained.

[0036] The collagen sheet is preferably composed of a collagen substrate and a plurality of collagen strings. For example, as shown in FIG. 2, a plurality of collagen strings 1 may be arranged on one surface of the collagen substrate 2. Alternatively, a part of the plurality of collagen strings may be arranged on one surface of the collagen substrate, and the remaining collagen strings may be arranged on the other surface of the collagen substrate. Alternatively, a part or all of the plurality of collagen strings may be embedded in the collagen substrate. The collagen strings arranged on the surface of the collagen substrate are preferably adhered to the surface of the collagen substrate.

[0037] When the collagen substrate has an orientation, the plurality of collagen strings are preferably arranged on the surface of the collagen substrate such that the orientation direction of the plurality of collagen strings coincides with the orientation direction of the collagen substrate. That the orientation directions of the plurality of collagen structures coincide means that the orientations they have are in the same direction among the plurality of collagen structures having an orientation. For example, in the collagen sheet 10 of FIG. 2, when the orientation direction of the collagen substrate 2 coincides with the orientation direction of the collagen string 1, the collagen substrate 2 has an orientation in the length direction (L2 direction).

[0038] When the collagen sheet contains a plurality of collagen strings, it is preferable that the plurality of collagen strings are arranged substantially parallel to each other so that the orientation directions of the plurality of collagen strings coincide with each other. The distance between the collagen strings is not particularly limited as long as the porosity in the collagen tube is 70 to 98%. For example, the distance d between the centers of adjacent collagen strings can be 100 to 400 μm. The distance d between the centers of adjacent collagen strings is preferably 150 to 350 μm, more preferably 160 to 300 μm, and even more preferably 170 to 300 μm.

[0039] The number of collagen strings contained in the collagen sheet is not particularly limited as long as the porosity in the collagen tube is 70 to 98%. The number of collagen strings can be appropriately selected according to the width W2 and thickness T2 of the collagen matrix, the inner diameter ID 20 of the collagen tube, and the diameter D1 of the collagen string. For example, when the width W2 and thickness T2 of the collagen matrix are 7 mm and 0.01 mm, respectively, the inner diameter ID 20 of the collagen tube is 3 mm, and the diameter D1 of the collagen string is 50 μm, the number of collagen strings can be 20 to 30, and preferably 20. The number of collagen strings with respect to the width W2 of the collagen matrix depends on the thickness of the collagen matrix and the diameter of the collagen string, but can be, for example, 1 to 5 strings / mm, or 2 to 3 strings / mm.

[0040] The collagen sheet composed of the collagen matrix and the collagen string can be produced by a known method. For example, a plurality of string-like collagen gels having axial orientation are arranged on the surface of the collagen matrix and dried to produce a collagen sheet.

[0041] When the collagen sheet does not contain collagen strings, the collagen sheet is composed only of the collagen matrix.

[0042] In the bone augmentation structure of this embodiment, the collagen sheet is accommodated in a collagen tube. When the collagen tube and the collagen sheet have orientation, it is preferable that the collagen sheet is accommodated in the collagen tube so that the orientation direction of the collagen sheet coincides with the orientation direction of the collagen tube. When the collagen sheet includes a plurality of collagen strings, it is preferable that the orientation direction of the plurality of collagen strings coincides with the orientation direction of the collagen tube.

[0043] 1 and 2, the collagen sheet 10 forms a wound body 11 and is housed in a collagen tube 20. The length L of the wound body 11 is 11 is equal to the length L2 of the collagen substrate 2. As shown in Figs. 1 and 2, the collagen sheet is preferably wound in a wound state and housed in a collagen tube. By winding the collagen sheet and housing it in a collagen tube as a wound body, it becomes easier to control the structure inside the collagen tube, and the shape retention of the bone augmentation structure is improved. When forming a wound collagen sheet, the collagen sheet is wound in a direction parallel to the orientation direction of the collagen strings. That is, in the wound collagen sheet, the axial direction of the wound body (L in Fig. 2) is 11 1, the collagen sheet roll 11 is preferably accommodated in the collagen tube 20 such that the axial direction of the roll 11 coincides with the axial direction of the collagen strings. This allows the collagen sheet 10 to be accommodated in the collagen tube 20 such that the orientation direction of the multiple collagen strings 1 coincides with the orientation direction of the collagen tube 20.

[0044] Second Embodiment A configuration example of the bone augmentation structure of the second embodiment will be described with reference to Fig. 4A and Fig. 4B. Fig. 4A is a perspective view of a bone augmentation structure 200, which is an example of the bone augmentation structure of this embodiment. Fig. 4B is a top view of the bone augmentation structure 200. In the bone growth structure 200, five collagen tubes 10a and four collagen tubes 10b are accommodated in the collagen tube 20. The collagen tubes 10a and 10b are tube-shaped collagen structures. The collagen tube 20 is the first collagen tube that forms the outer shell of the bone growth structure. The collagen tubes 10a and 10b are the second collagen tubes accommodated in the first collagen tube 20.

[0045] The same collagen tube 20 as that in the first embodiment can be used.

[0046] The collagen tubes 10a and 10b are collagen tubes having an outer diameter and an inner diameter smaller than those of the collagen tube 20. The collagen tube 10b is a collagen tube having an outer diameter and an inner diameter smaller than those of the collagen tube 10a. Five collagen tubes 10a are arranged in a cross shape in the collagen tube 20. One collagen tube 10b is arranged between adjacent collagen tubes 10a close to the inner circumference of the collagen tube 20. Therefore, four collagen tubes 10a and four collagen tubes 10b are alternately arranged along the inner circumference of the collagen tube 20.

[0047] The length L of the collagen tube 10a 10a and the length L of the collagen tube 10b 10b are preferably substantially equal to the length L of the collagen tube 20. 20

[0048] The outer diameter OD of the collagen tube 10a 10a is the inner diameter ID of the collagen tube 20 20and can be appropriately selected according to the number of collagen tubes 10a accommodated in the collagen tube 20. In the bone growth structure 200, three collagen tubes 10a are accommodated in the radial direction of the collagen tube 20. Therefore, the outer diameter OD 10a of the collagen tube 10a 20 is equal to or less than 1 / 3 of the inner diameter ID 10a of the collagen tube 20. In this case, it is preferable that the outer diameter OD 20 of the collagen tube 10a is approximately equal to 1 / 3 of the inner diameter ID 10a of the collagen tube 20. The outer diameter OD 20 of the collagen tube can be, for example, 0.2 to 7 mm. The outer diameter OD

[0049] of the collagen tube is preferably, for example, 0.3 to 5 mm, more preferably 0.7 to 3 mm, still more preferably 1 to 3 mm, and particularly preferably 1 to 2 mm. 10a The thickness T 10a of the collagen tube 10a can be, for example, 5 to 200 μm. The thickness T

[0050] of the collagen tube is preferably, for example, 20 to 100 μm, more preferably 30 to 80 μm, still more preferably 30 to 60 μm, and particularly preferably 30 to 50 μm. 10a The inner diameter ID 10a of the collagen tube 10a can be, for example, 0.2 to 7 mm. The inner diameter ID 20 of the collagen tube 10a is 10a and the thickness T 10a of the outer diameter OD of the collagen tube 10a.

[0051] The outer diameter OD 10b of the collagen tube 10b is 20 the inner diameter ID of the collagen tube 20, the outer diameter OD of the collagen tube 10a accommodated in the collagen tube 2010a And it can be appropriately selected according to the number, and the number of the collagen tubes 10b accommodated in the collagen tube 20. For example, the outer diameter OD of the collagen tube 10b 10b can be about 1 / 4 to 3 / 4 of the outer diameter OD of the collagen tube 10a, and 1 / 3 to 2 / 3 of the outer diameter OD of the collagen tube 10a is preferable. The outer diameter OD of the collagen tube 10b 10a can be about 1 / 4 to 3 / 4 of the outer diameter OD of the collagen tube 10a, and 1 / 3 to 2 / 3 of the outer diameter OD of the collagen tube 10a is preferable. The outer diameter OD of the collagen tube 10b 10a can be about 1 / 4 to 3 / 4 of the outer diameter OD of the collagen tube 10a, and 1 / 3 to 2 / 3 of the outer diameter OD of the collagen tube 10a is preferable. The outer diameter OD of the collagen tube 10b 10b can be, for example, about the outer diameter OD of the collagen tube 10a 10a of 10a. The outer diameter OD of the collagen tube 10b 10b can be, for example, 0.1 to 5 mm. The outer diameter OD of the collagen tube 20 can be, for example, preferably 0.2 to 3 mm, more preferably 0.3 to 2 mm, still more preferably 0.5 to 1 mm, and particularly preferably 0.5 to 0.8 mm.

[0052] The thickness T of the collagen tube 10b 10b can be, for example, 5 to 200 μm. The thickness T of the collagen tube 10b can be, for example, preferably 20 to 100 μm, more preferably 30 to 80 μm, still more preferably 30 to 60 μm, and particularly preferably 30 to 50 μm.

[0053] The inner diameter ID of the collagen tube 10b 10b can be, for example, 0.1 to 5 mm. The inner diameter ID of the collagen tube 10b can be, for example, preferably 0.2 to 3 mm, more preferably 0.3 to 2 mm, still more preferably 0.5 to 1 mm, and particularly preferably 0.5 to 0.8 mm. The inner diameter ID of the collagen tube 10b 10b is defined by the outer diameter OD 10b and the thickness T 10b of the collagen tube 10b.

[0054] The collagen tube 10a preferably has axial orientation. The collagen tube 10b preferably has axial orientation. When the collagen tube 20, the collagen tube 10a, and the collagen tube 10b each have axial orientation, it is preferable to align the axial directions of the collagen tube 10a and the collagen tube 10b with the axial direction of the collagen tube 20 and accommodate the collagen tube 10a and the collagen tube 10b within the collagen tube 20. Thereby, the orientation directions of the collagen tube 10a and the collagen tube 10b can be made to coincide with the orientation direction of the collagen tube 20.

[0055] The collagen tube 10a and the collagen tube 10b may each contain a collagen string. The number of collagen strings contained in the collagen tube 10a is not particularly limited as long as the porosity within the collagen tube 20 is 70 - 98%. The number of collagen strings contained in the collagen tube 10b is not particularly limited as long as the porosity within the collagen tube 20 is 70 - 98%. For example, when the outer diameter of the collagen tube 10a is 1 mm, the collagen tube 10a can contain 4 - 6 collagen strings. For example, when the outer diameter of the collagen tube 10b is 0.5 mm, the collagen tube 10b can contain 2 - 4 collagen strings.

[0056] When the collagen tubes 10a and 10b have orientation and contain collagen strings, it is preferable that the orientation directions of the collagen tubes and the collagen tubes 10b are the same as the orientation direction of the collagen strings. For example, when the collagen tube 10a has axial orientation, the collagen string is preferably arranged in the collagen tube 10a such that the axial direction of the collagen string coincides with the axial direction of the collagen tube 10a. For example, when the collagen tube 10b has axial orientation, the collagen string is preferably arranged in the collagen tube 10b such that the axial direction of the collagen string coincides with the axial direction of the collagen tube 10b. The method of arranging the collagen string with respect to the collagen tube 10a or the collagen tube 10b can be the same as that of the collagen sheet in the first embodiment. The collagen tubes 10a and 10b may be formed by shaping the collagen sheet in the first embodiment into a tube shape.

[0057] <Modification Example> The second collagen tubes accommodated in the first collagen tube may all have the same size. The second collagen tubes accommodated in the first collagen tube may be composed of three or more types of collagen tubes with different outer diameters. A second collagen tube may be accommodated in the first collagen tube, and a third collagen tube may be accommodated in the second collagen tube. The number of the second collagen tubes accommodated in the first collagen tube may be one or a plurality, but a plurality is preferable. The number of the second collagen tubes can be, for example, 2 to 20, 3 to 15, or 5 to 12.

[0058] ≪Porosity≫ The structure for bone growth of this embodiment has a porosity within the range of 70 to 98% in the collagen tube (the first collagen tube). By setting the porosity in the collagen tube within the above range, when transplanted into the living body, while maintaining the shape retention of the bone growth structure, cells are more easily incorporated into the bone growth structure. The porosity is preferably 75 to 98%, more preferably 80 to 98%, even more preferably 85 to 97%, and particularly preferably 90 to 95%.

[0059] The porosity in the collagen tube can be calculated by the following formula (1). Porosity (%) = (V 20 - V 10 ) / V 20 × 100 (1) V 20 : The volume inside the collagen tube V 10 : The volume of the collagen structure accommodated inside the collagen tube

[0060] The volume V of the inside of the collagen tube 20 can be calculated by the following formula (2). V 20 = (1 / 2 × ID 20 ) 2 π × L 20 (2) ID 20 : The inner diameter of the collagen tube L 20 : The length of the collagen tube

[0061] When the collagen structure accommodated inside the collagen tube is in a sheet shape, the volume V of the collagen structure 10 can be calculated by the following formula (3). When the collagen structure does not contain collagen strings, n1 = 0. V 10 = (1 / 2 × D1) 2 π × L1 × n1 + L2 × W2 × T2 (3) ID 20 : The inner diameter of the collagen tube L 20: Length of the collagen tube D1: Diameter of the collagen string L1: Length of the collagen string n1: Number of collagen strings L2: Length of the collagen matrix W2: Width of the collagen matrix T2: Thickness of the collagen matrix

[0062] When the collagen structure accommodated in the collagen tube is in the shape of a tube, the volume V of the collagen structure 10 can be calculated by the following formula (4). When the collagen structure does not contain collagen strings, n 1a = 0 V 10 =[(1 / 2 × D 1a ) 2 π × L 1a × n 1a +{(1 / 2 × OD 10a ) 2 π - (1 / 2 × ID 10a ) 2 π} × L 10a × m 10a (4) D 1a : Diameter of the collagen string L 1a : Length of the collagen string n 1a : Number of collagen strings contained in one collagen structure OD 10a : Outer diameter of the tube-shaped collagen structure ID 10a : Inner diameter of the tube-shaped collagen structure L 10a : Length of the tube-shaped collagen structure m 10a : Number of tube-shaped collagen structures

[0063] When the tube-shaped collagen structure is composed of two or more tube-shaped collagen structures a1 to ai with different outer diameters, the volume V of the collagen structure 10can be calculated by the following formula (5). V 10 =[(1 / 2×D 1a1 ) 2 π×L 1a1 ×n 1a1 +{(1 / 2×OD 10a1 ) 2 π-(1 / 2×ID 10a1 ) 2 π}×L 10a1 ×m 10a1 +···+[(1 / 2×D 1ai ) 2 π×L 1ai ×n 1ai +{(1 / 2×OD 10ai ) 2 π-(1 / 2×ID 10ai ) 2 π}×L 10ai ×m 10ai (5) D 1a1 : Diameter of the collagen string contained in the collagen structure a1 L 1a1 : Length of the collagen string contained in the collagen structure a1 n 1a1 : Number of collagen strings contained in one collagen structure a1 OD 10a1 : Outer diameter of the tubular collagen structure a1 ID 10a1 : Inner diameter of the tubular collagen structure a1 L 10a1 : Length of the tubular collagen structure a1 m 1a1 : Number of the tubular collagen structures a1 D 1ai : Diameter of the collagen string contained in the collagen structure ai L 1ai : Length of the collagen string contained in the collagen structure ai n 1ai : Number of collagen strings contained in one collagen structure ai OD 10ai : Outer diameter of the tubular collagen structure ai ID10ai : Inner diameter of the tube-shaped collagen structure ai L 10ai : Length of the tube-shaped collagen structure ai m 1ai : Number of the tube-shaped collagen structures ai

[0064] When the thickness of the tube-shaped collagen structure is small, the tube-shaped collagen structure can be regarded as a sheet shape obtained by axially cutting the tube, and the volume V of the collagen structure 10 can be calculated. In this case, the volume V 10 of the collagen structure can be calculated by the following formula (6). V 10 ={(1 / 2×D 1a1 ) 2 π×L 1a1 ×n 1a1 +OD 10a1 ×L 10a1 ×T 10a1}×m 10a1 +···+{(1 / 2×D 1ai ) 2 π×L 1ai ×n 1ai +OD 10ai ×L 10ai ×T 10ai}×m 10ai (6) D 1a1 : Diameter of the collagen string contained in the collagen structure a1 L 1a1 : Length of the collagen string contained in the collagen structure a1 n 1a1 : Number of the collagen strings contained in one collagen structure a1 OD 10a1 : Outer diameter of the tube-shaped collagen structure a1 L 10a1 : Length of the tube-shaped collagen structure a1 T 10a1 : Thickness of the tube-shaped collagen structure a1 m 1a1 : Number of the tube-shaped collagen structures a1 D 1ai: Diameter of the collagen string contained in the collagen structure ai L 1ai : Length of the collagen string contained in the collagen structure ai n 1ai : Number of collagen strings contained in one collagen structure ai OD 10ai : Outer diameter of the tube-shaped collagen structure ai L 10ai : Length of the tube-shaped collagen structure a i T 10ai : Thickness of the tube-shaped collagen structure a i m 1ai : Number of the tube-shaped collagen structures ai

[0065] ≪Usage Method≫ The bone growth structure of the present embodiment can be used to grow bone at a desired position in vivo. The organism to which the bone growth structure of the present embodiment is applied is not particularly limited as long as it is an organism having bones, and it is preferably applied to vertebrates. As vertebrates, mammals are preferred, and for example, it can be suitably used for humans or mammals other than humans. Mammals other than humans are not particularly limited, but include primates (such as monkeys, chimpanzees, gorillas), rodents (such as mice, hamsters, rats), rabbits, dogs, cats, cows, goats, sheep, horses, etc.

[0066] The application site of the bone growth structure of the present embodiment is not particularly limited, and it can be applied to a desired site where bone growth is required. Examples of sites where bone growth is required include alveolar bone. In implant treatment, since an implant is implanted into the alveolar bone, sufficient bone mass of the alveolar bone is required. Therefore, when the alveolar bone is lost due to periodontal disease or the like, implant treatment becomes difficult. In such a case, the bone growth structure of the present embodiment can be used to grow the alveolar bone.

[0067] ​​The bone growth structure of this embodiment can perform bone growth, for example, by forming an embedding hole in the bone at the site where bone growth is to be performed and embedding the bone growth structure of this embodiment in the embedding hole. The embedding hole is preferably formed so as to reach the bone marrow, as shown in the lower figure of FIG. 9. Thereby, when the bone growth structure is embedded in the embedding hole, the bone growth structure comes into contact with the bone marrow fluid, and the bone marrow fluid is absorbed into the structure. As shown in the lower figure of FIG. 9, the bone growth structure is preferably embedded in the embedding hole so as to protrude from the remaining bone edge. The height protruding from the remaining bone edge is not particularly limited and can be set according to the height at which bone growth is required. The bone growth structure may be embedded in a dry state, or may be immersed in an appropriate buffer solution or the like to be in a wet state and then embedded.

[0068] After the bone growth structure is embedded, the bone marrow fluid is taken into the embedded bone growth structure. Differentiation of mesenchymal stem cells contained in the bone marrow fluid into bone cells is induced in the bone growth structure and in the peripheral part of the bone growth structure, and bone is grown. In this process, the bone growth structure is absorbed into the bone tissue. Therefore, after the bone growth structure is embedded, it is only necessary to perform timely follow-up observation.

[0069] The bone growth structure of this embodiment is composed of a collagen tube and a collagen structure housed in the collagen tube. Thereby, when the bone growth structure is embedded in the bone and comes into contact with the bone marrow fluid, capillary action works in the collagen tube, and the absorption of the bone marrow fluid into the bone growth structure is promoted. In addition, since the porosity in the collagen tube is 70 to 98%, there is a sufficient space for retaining the bone marrow fluid, and bone regeneration is promoted.

[0070] When the collagen tube has an axial orientation, the movement of the bone marrow fluid in the axial direction of the collagen tube is promoted. Thereby, bone growth in the axial direction of the collagen tube is promoted.

[0071] When the orientation direction of the collagen structure accommodated in the collagen tube coincides with the orientation direction of the collagen tube, the movement of bone marrow fluid in the direction of their orientation is more promoted. Thereby, bone growth in the axial direction of the collagen tube is more promoted.

[0072] When the collagen structure accommodated in the collagen tube contains a collagen string, when the bone growth structure is implanted into the bone, the resistance to the pressure from the surrounding mucosa increases and the shape retention property is improved.

[0073] When the collagen structure accommodated in the collagen tube is in a tube shape, when the bone growth structure is implanted into the bone, the resistance to the pressure from the surrounding mucosa increases and the shape retention property is improved. By adjusting the number and size of the tube-shaped collagen structures, the variation in the porosity within the collagen tube can be controlled. Furthermore, by combining and using two or more types of tube-shaped collagen structures having different outer diameters, it becomes easier to control the variation in the porosity within the collagen tube.

[0074] The bone growth structure of the present embodiment has high shape retention property and can retain its shape even when implanted in a living body. The shape retention force serves as a resistance to mucosal invasion in a living body. Therefore, it is possible to prevent mucosal invasion that heals at an earlier stage than bone regeneration and retain the space for bone growth.

[0075] The bone growth structure of the present embodiment has high cell adhesiveness and can hold many cells inside the structure. Therefore, it is possible to induce the differentiation of many cells within the bone growth structure, and bone growth is promoted.

[0076] The bone growth structure of the present embodiment improves the ALP activity of the cells within the bone growth structure. ALP activity is a differentiation marker from mesenchymal stem cells to osteoblasts. A high ALP activity means that the induction of differentiation into osteoblasts is promoted.

[0077] When implanted into bone, the bone growth structure of the present embodiment can grow bone up to above the existing bone. Therefore, even in patients with reduced bone mass of the existing bone, the bone mass can be effectively increased.

[0078] The bone growth structure of the present embodiment can simply and stably perform bone growth only by being implanted into the bone at a desired site where bone growth is required. Therefore, it can be suitably used as a dental material for dental treatment such as implant treatment. The bone growth structure of the present embodiment can be particularly suitably used for alveolar bone growth.

[0079] The bone growth structure of the present embodiment can perform bone growth at a bone density in a state suitable for implant surgery. Bone density can be classified into the following Type I to Type IV (see FIG. 5). The bone density suitable for implant surgery is Type II and Type III. In Type I, bone tissue is strongly destroyed during implant surgery (thermal destruction of the tissue around the hole), and the bone bonding of the implant is poor. In Type IV, it is difficult to obtain initial fixation during implant implantation, so the bone bonding of the implant is poor. The bone growth structure of the present embodiment can grow bone in a state of Type II or Type III bone density. Type I (Dense Bone): Thick cortical bone and highly dense cancellous bone. Type II, III (Medium Bone): Cortical bone of medium thickness and cancellous bone with high to medium density. Type IV: Thin cortical bone and low-density cancellous bone.

[0080] [Other Aspects] In one aspect, the present invention provides a bone growth method including a step of implanting the bone growth structure of the above embodiment into bone. In one aspect, the present invention provides a method for growing alveolar bone, including a step of implanting the bone growth structure of the above embodiment into the alveolar bone. In one aspect, the present invention provides a method for implanting an implant, including a step of implanting the bone growth structure of the above-described embodiment into bone to promote bone growth, and a step of implanting an implant into the bone-grown site. In one aspect, the present invention provides a method for implanting an implant, including a step of implanting the bone growth structure of the above-described embodiment into the alveolar bone to promote bone growth, and a step of implanting an implant into the alveolar bone site where bone growth has occurred.

Example

[0081] Hereinafter, the present invention will be described by experimental examples, but the present invention is not limited to the following experimental examples.

[0082] [Examination of the shape retention of the collagen sheet structure] Regarding the following structures, the shape retention was examined. Each example of the structure was placed in a 20 mm cell culture dish containing 1 mL of αMEM medium, and the shape change of the structure was observed after 6 hours and 24 hours.

[0083] Structure 1: A structure formed by laminating collagen sheets (length 7 mm, width 10 mm, thickness 0.01 mm) (manufactured by Atree Co., Ltd.) into a cube with a thickness of 7 mm and a diameter of 10 mm. The collagen sheet used contained 20 collagen strings with a diameter of 50 μm having an orientation in the axial direction. In the collagen sheet, the 20 collagen strings were arranged substantially parallel to each other at an interval such that the distance between the centers of adjacent collagen strings was about 285 μm. The porosity of the structure was 92%.

[0084] Structure 2: Terplug (size SS; diameter 8 mm, length 15 mm) (manufactured by Terumo Corporation).

[0085] Structure 3: A structure was fabricated in the same manner as Structure 1, except that a collagen sheet containing 30 collagen strings was used. In the collagen sheet, the 30 collagen strings were arranged at intervals such that the distance between the centers of adjacent collagen strings was approximately 177 μm. The porosity of the structure was 88%.

[0086] The results are shown in Fig. 6. In Fig. 6, 1 to 3 indicate Structures 1 to 3, respectively. In any of the structures, as time passed, the αMEM medium was absorbed into the structure. In Structures 1 and 3, the shape was maintained even after 24 hours. On the other hand, in Structure 2, the shape could not be maintained after 24 hours and it had fallen over. From this result, it was confirmed that Structures 1 and 3 have better shape retention than Structure 2. Structure 1 had a faster absorption rate of the αMEM medium compared to Structure 3. This was considered to be because the porosity of Structure 1 was larger. It is presumed that a faster absorption rate of the medium makes it easier for cells to be incorporated into the structure when transplanted in vivo and promotes bone growth. Therefore, in the following examples, a bone growth structure was fabricated with reference to the porosity of Structure 1.

[0087] [Fabrication of Bone Growth Structure (1)] (Example 1) A collagen sheet (length: 7 mm, width: 20 mm, thickness: 0.01 mm) (manufactured by Atorie Co., Ltd.) was wound and accommodated in a collagen tube (inner diameter: 3 mm, length: 7 mm, thickness: 40 μm) (oriented collagen seamless tube, manufactured by Atorie Co., Ltd.) having orientation in the axial direction, thereby producing a bone growth structure. As the collagen sheet, one containing about 60 collagen strings with a diameter of 50 μm having orientation in the axial direction was used. In the collagen sheet, about 60 collagen strings were arranged substantially parallel to each other at intervals such that the distance between the centers of adjacent collagen strings was about 285 μm. The porosity in the collagen tube of the bone growth structure was 95%. The produced bone growth structure is shown in Fig. 3. The bone growth structure of Example 1 has the same porosity as the above Structure 1, but since the outer shell is covered with a collagen tube, it is considered that the shape retention is improved compared to Structure 1.

[0088] (Comparative Example 1) A Telplug (size SS; diameter: 8 mm, length: 15 mm) (manufactured by Terumo Corporation) was purchased and used as a bone growth structure.

[0089] [Evaluation of Cell Adhesion] (Preparation of Cells) As cells, rat bone marrow-derived mesenchymal stem cells collected from 8-week-old male Sprague-Dawley rats were used. By the 4th day after cell collection, only the cells attached to a 100 mm cell culture dish were separated and passaged. Cells up to the 7th day of culture were used for the test. The cell concentration seeded in the cell culture dish was 3×10 4 cells / cm 2 2. αMEM was used as the medium. The culture temperature was 37°C.

[0090] (Measurement of Cell Adhesion) 1 mL of cell culture medium was placed in a 20 mm cell culture dish (12-well plate), and the bone growth structures of Example 1 and Comparative Example 1 were placed, and the cells were cultured at 37°C. 24 hours, 48 hours, and 72 hours after the bone growth structure was placed, the bone growth structure was transferred to another cell culture dish, and the absorbance was measured with an absorbance meter (ELISA) using WST-8 (Roche Applied Science). Furthermore, the bone growth structure was treated with EDTA-4Na, and the cell count was measured with a hemocytometer.

[0091] The results are shown in Fig. 7. The number of adherent cells in Example 1 was about twice that in Comparative Example 1. From this result, it was confirmed that the bone growth structure of Example 1 has excellent cell adhesiveness. The increase in the number of adherent cells indicates that there are many cells retained in the bone growth structure, which is advantageous for bone growth. The presence of many cells in the bone growth structure is advantageous for cell proliferation after cell adhesion, and as a result, it is advantageous for bone regeneration after cell differentiation.

[0092] [Evaluation of alkaline phosphatase (ALP) activity] Cells were prepared in the same manner as in [Evaluation of cell adhesiveness]. 1 mL of cell culture medium was placed in a 20 mm cell culture dish (12-well plate), and the bone growth structures of Example 1 and Comparative Example 1 were placed, and the cells were cultured at 37°C. 5 days and 10 days after the bone growth structure was placed, ALP-positive cells were stained using 0.9 mM naphthol AS-MX and 1.8 mM fast red TR. In addition, the bone growth structure was longitudinally sectioned at the center of the cylinder, and the stained area of the longitudinal section was measured. Furthermore, the ALP activity was quantified using p-nitrophenyl-phosphate (LabAssay ATP, Wako Pure Chemicals).

[0093] The results are shown in Fig. 8. The ALP activity in Example 1 was higher than that in Comparative Example 1. From this result, it was confirmed that the bone growth structure of Example 1 has the effect of improving ALP activity. ALP activity is a marker for confirming the differentiation of mesenchymal stem cells into osteoblasts. A high ALP activity is considered to indicate that the cells in the bone growth structure are induced to differentiate into osteoblasts, which is an advantageous state for bone growth.

[0094] [Implantation test in rat femur (1)] A bone defect with a diameter of 4 mm and a depth of 2 mm was created in the rat femur, and the bone growth structures of Example 1 and Comparative Example 1 were implanted into the defect site. The bone defect with a depth of 2 mm penetrates the cortical bone and reaches the bone marrow. When a bone growth structure with a length of 7 mm is implanted into the bone defect, the bone growth structure reaches the bone marrow and expands by absorbing bone marrow fluid and blood. The bone growth structure was implanted into the femur so as to protrude 2 mm vertically from the residual bone edge (see Fig. 9). 30 days after the implantation of the bone growth structure, the femur at the implantation site was collected and macroscopic observation was performed. Furthermore, a section of the femur was prepared and observed by Villanueva Goldner (VG) staining.

[0095] The results are shown in Fig. 10. Fig. 10A shows the femur implanted with the bone growth structure of Example 1. Fig. 10B shows the femur implanted with the bone growth structure of Comparative Example 1. In the case of implanting the bone growth structure of Example 1, bone was observed above the existing bone. Also, from the observation of the section, it was confirmed that the bone formed above the existing bone was completely ossified. On the other hand, in the case of implanting the bone growth structure of Comparative Example 1, no bone formation above the existing bone was observed. From this result, it was confirmed that the bone growth structure of Example 1 can promote bone growth higher than the existing bone with a simple procedure.

[0096] [Fabrication of bone growth structure (1)] (Example 2) Axially oriented collagen tube A (outer diameter 1 mm, length 7 mm, thickness 50 μm, containing 4 to 5 collagen strings with a diameter of 50 μm) (manufactured by Atorie Co., Ltd.), and axially oriented collagen tube B (outer diameter 0.5 mm, length 7 mm, thickness 40 μm, containing 2 collagen strings with a diameter of 50 μm) (manufactured by Atorie Co., Ltd.) were prepared. Five collagen tubes A and four collagen tubes B were accommodated in an axially oriented collagen tube (inner diameter 3 mm, length 7 mm, thickness 50 μm) (oriented collagen seamless tube, manufactured by Atorie Co., Ltd.) in the arrangement shown in FIGS. 4A and 4B to produce a bone growth structure. The porosity of the collagen tube in the bone growth structure calculated by the above formula (5) was 84%.

[0097] (Comparative Example 2) A Telplug (size SS; diameter 8 mm, length 15 mm) (manufactured by Terumo Corporation), similar to that in Comparative Example 1, was used as the bone growth structure.

[0098] [Implantation test in rat femur (2)] In the same manner as in [Implantation test in rat femur (1)], the bone growth structure of Example 2 or Comparative Example 2 was implanted into the rat femur. Two months after the implantation of the bone growth structure, the femur at the implantation site was collected and macroscopic observation was performed. Furthermore, the femur was observed by computed tomography (CT).

[0099] FIG. 11A is a photograph of a rat femur collected two months after implanting the bone growth structure. The upper femur is the one implanted with the bone growth structure of Example 2, and the lower femur is the one implanted with the bone growth structure of Comparative Example 2. The cross-sectional shapes of these rat femurs were regarded as elliptical, and the major axis and minor axis were measured (see FIG. 11B). The results are shown in FIGS. 12A and 12B. FIG. 12A shows the measurement result of the major axis, and FIG. 12B shows the measurement result of the minor axis. It was confirmed that both the major axis and the minor axis were increased in the case where the bone growth structure of Example 2 was implanted compared with the case where the bone growth structure of Comparative Example 2 was implanted.

[0100] Fig. 13 is a CT image of a rat femur taken two months after the implantation of the bone augmentation structure. In the case where the bone augmentation structure of Example 2 was implanted, it was confirmed that the bone extended in the direction in which the bone augmentation structure was inserted. It was also confirmed that cancellous bone was proliferated within the bone marrow. From this result, it was inferred that the bone quality was also good. On the other hand, in the case where the bone augmentation structure of Comparative Example 2 was implanted, healing of the implantation site was confirmed, but no increase in bone mass was observed.

[0101] FIG. 14 is a CT image of a cross section of a rat femur taken two months after the implantation of the bone augmentation structure. In the case where the bone augmentation structure of Example 2 was implanted, the shape of the bone augmentation structure before replacement with bone was confirmed. In addition, a spongy bone-like opaque image was observed from the insertion site of the bone augmentation structure to the center of the femur. The cortical bone was also thickened. From these observations, it was considered that the bone density of the case where the bone augmentation structure of Example 2 was implanted was close to medium (Type II or Type III). On the other hand, in the case where the bone augmentation structure of Comparative Example 2 was implanted, healing of the insertion site of the bone augmentation structure was confirmed. However, no increase in bone mass was observed, and the cortical bone was thin. A small amount of cancellous bone-like opaque image was observed in the center of the femur. From these observations, it was considered that the bone density of the case where the bone augmentation structure of Comparative Example 2 was implanted was close to soft (Type IV).

[0102] The above results demonstrate that by implanting the bone augmentation structure of Example 2, bone augmentation can be achieved with a bone density suitable for implant surgery. [Industrial Applicability]

[0103] According to the present invention, a bone augmentation structure capable of augmenting bone simply and stably is provided. [Explanation of symbols]

[0104] 1. Collagen String 2 Collagen matrix 10 Collagen sheets (sheet-shaped collagen structures) 10a, 10b Collagen tubes (tube-shaped collagen structures) 11 Wound body 20 Collagen tubes 100, 200 Structures for bone growth

Claims

1. A collagen tube and, A collagen structure accommodated in the collagen tube, comprising: The porosity within the collagen tube is 70-98%, The collagen tube has orientation in the axial direction of the collagen tube, A structure for bone growth.

2. (Deleted)

3. The collagen structure has orientation, The collagen structure is accommodated in the collagen tube such that the direction of orientation of the collagen structure coincides with the direction of orientation of the collagen tube. The structure for bone growth according to Claim 1.

4. The collagen structure includes a plurality of collagen strings having orientation in the axial direction, and the direction of orientation of the plurality of collagen strings coincides with the direction of orientation of the collagen tube. The structure for bone growth according to Claim 3.

5. In the collagen structure, the plurality of collagen strings are arranged such that the distance between the centers of adjacent collagen strings is 100-400 μm. The structure for bone growth according to Claim 4.

6. The collagen structure is a sheet-shaped collagen structure. The structure for bone growth according to any one of Claims 1, 3-5.

7. The sheet-shaped collagen structure forms a wound body and is accommodated in the collagen tube. The structure for bone growth according to Claim 6.

8. The collagen structure is a tube-shaped collagen structure. The structure for bone growth according to any one of Claims 1, 3-5.

9. A plurality of the tube-shaped collagen structures are accommodated in the collagen tube. The structure for bone growth according to Claim 8.

10. The plurality of tube-shaped collagen structures are composed of two or more types of tube-shaped collagen structures having different outer diameters. The structure for bone growth according to Claim 9.

11. A dental material. The structure for bone growth according to any one of Claims 1, 3-10.

12. For alveolar bone growth. The structure for bone growth according to Claim 11.

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