Molded bodies derived from extracellular matrix and their molded bodies

Abstract

To provide a method with which it is possible to manufacture a compact that has a given shape and is derived from an extracellular matrix.SOLUTION: A compact derived from an extracellular matrix is made up of a plurality of molded body parts containing extracellular matrix powder connected to each other in which two or more of the plurality of molded body parts contain extracellular matrix powders derived from structures different in kind.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a molded body derived from an extracellular matrix and such a molded body.

Background Art

[0002] A decellularized tissue obtained by removing cells from a biological tissue, which is composed of cells and an extracellular matrix (ECM), is suggested to have an ECM composition and structure equivalent to that of a living body and to induce tissue regeneration by assimilating with surrounding tissues after transplantation. Also, decellularized tissue powders and decellularized tissue gels have been studied and applied as tissue regeneration and cell culture substrates. However, it is difficult to produce a decellularized tissue with materials other than the shape, composition, and mechanical strength present in the biological tissue as the raw material. It is difficult to apply decellularized tissue powder other than for inducing wound healing, and gels have problems such as low mechanical strength and ECM denaturation due to solubilization. Also, although attempts have been made to use a disk-shaped product made from decellularized tissue powder using a mold as a scaffold (Non-Patent Document), when using a conventional press machine (Figure 2) for solidifying the powder, it is difficult to obtain a molded body with an arbitrary shape, and the material density on the surface of the obtained molded body does not become uniform (the material density on the surface other than the pressing direction (vertical direction) is lower compared to the material density on the surface in the pressing direction (side surface)).

Prior Art Documents

Non-Patent Documents

[0003]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] An object of the present invention is to provide a method capable of manufacturing a molded body derived from an extracellular matrix having an arbitrary shape. [Means for solving the problem]

[0005] Under these circumstances, the inventors, after trial and error with various methods, discovered that the above problems could be solved by adapting a technique used in ceramic molding, a field entirely different from the biochemistry field to which the present invention belongs. Based on this new finding, the inventors further investigated the extracellular matrix powder used as a material, the molding conditions, etc., and completed the present invention. Accordingly, the present invention provides the following:

[0006] Item 1. A molded body derived from extracellular matrix, comprising multiple molded body portions containing extracellular matrix powder joined together, wherein two or more of the multiple molded body portions contain extracellular matrix powder derived from different types of tissue.

[0007] Item 2. Process of filling a mold with material powder containing extracellular matrix powder. The process of placing a mold filled with the material powder into a liquid. The process of pressurizing the liquid in which the mold is placed. A method for producing an extracellular matrix-derived molded article, including the above.

[0008] Item 3. The method according to item 2, wherein the extracellular matrix powder is a bio-derived powder.

[0009] Item 4. The method according to Item 2 or 3, wherein the mold consists of at least one selected from the group consisting of silicone resin, rubber, pulp, polyethylene terephthalate, aluminum, and stainless steel.

[0010] Item 5. Extracellular matrix-derived material obtained by the method described in any one of items 2 to 4.

[0011] Item 6. A molded body made by pressing a material powder containing extracellular matrix powder with two molds, wherein the molded body has irregularities on surfaces other than the horizontal plane relative to the two molds. [Effects of the Invention]

[0012] According to the present invention, it is possible to provide a method for producing a molded body derived from an extracellular matrix having an arbitrary shape.

Brief Description of the Drawings

[0013] [Figure 1] The schematic diagram of the step of filling a mold with a material powder containing an extracellular matrix powder in the present invention is shown. [Figure 2] The explanatory diagram of a conventional press machine for solidifying the powder is shown. [Figure 3] The schematic diagram of various embodiments of the method of the present invention is shown. [Figure 4] The photograph of the mold used in Example 1 and the obtained molded body is shown. [Figure 5] The photograph of the molded body obtained in Example 2 is shown. [Figure 6] The photograph of the mold used in Example 3-1 and the obtained molded body is shown. [Figure 7] The photograph of the mold used in Example 3-2 and the obtained molded body is shown. [Figure 8] The photograph of the molded body obtained in Example 4 is shown. [Figure 9] The outline and results of the test in Example 5 are shown.

Modes for Carrying Out the Invention

[0014] Method for producing molded bodies derived from extracellular matrix The present invention includes a step of filling a mold with a material powder containing an extracellular matrix powder a step of placing the mold filled with the extracellular matrix powder in a liquid a step of pressurizing the liquid in which the mold is placed and provides a method for producing a molded body derived from an extracellular matrix.

[0015] In the present invention, examples of the extracellular matrix include those derived from various tissues, such as the brain, eye, thyroid gland, trachea, esophagus, stomach, liver, kidney, gallbladder, pancreas, intestine (small intestine, large intestine (colon, rectum, etc.)), lung, bladder, urethra, prostate, spinal cord, cartilage, bone marrow, tendon, joint, ligament, blood vessel, muscle, skin, uterus, ovary, testis, placenta, tooth, gingiva, tongue, etc. The extracellular matrix powder can be produced by removing cells from these tissues according to a method known per se. The extracellular matrix powder includes not only the decellularized tissue powder obtained by removing cells from the above tissues, but also powders derived from other sources (such as collagen powder) other than the decellularized tissue powder. As the extracellular matrix powder, those derived from one of these tissues may be used, or those derived from two or more of these tissues may be used in combination. Examples of the extracellular matrix include those derived from mammals, birds, etc. Examples of mammals include humans, mice, rats, dogs, cats, monkeys, cows, horses, sheep, goats, hamsters, pigs, etc., and preferably humans.

[0016] The shape of the extracellular matrix powder is not particularly limited, and examples include substantially spherical (including spherical), plate-like, fibrous, etc. The average particle diameter of the extracellular matrix powder is also not particularly limited, and examples include those having an average particle diameter of 500 to 0.01 μm, preferably 250 to 1 μm. The average particle diameter of the extracellular matrix powder can be measured by morphological observation using a microscope (scanning electron microscope, stereomicroscope, etc.), photon correlation method (DLS), or laser diffraction / scattering method (SLS).

[0017] As a material powder containing extracellular matrix powder, the extracellular matrix powder itself may be used as the material powder, or a mixture of extracellular matrix powder and other materials may be used as the material powder. When mixing extracellular matrix powder with other materials, for example, NaCl, polysaccharides, proteins, enzymes, sodium bicarbonate, etc., can be used. These other materials may be used individually or in combination of two or more. For example, a molded body can be made by mixing NaCl with extracellular matrix powder, and then removing the NaCl to obtain a porous molded body. When mixing extracellular matrix powder with other materials, the proportion of extracellular matrix powder in the material powder is not limited, but can be appropriately adjusted within ranges such as 70% by mass or more, 80% by mass or more, 90% by mass or more, 95% by mass or more, 97% by mass or more, 99% by mass or more, etc.

[0018] In the present invention, a step is performed to fill a hollow mold with a material powder containing extracellular matrix powder. As illustrated by the schematic diagram shown in Figure 1, material powder 1 containing extracellular matrix powder is filled into mold 2, and material powder 1' containing extracellular matrix powder is filled into mold 2'. In the present invention, the mold is not particularly limited as long as it is such that, in the pressurizing step described later, pressure is transmitted to the material filled inside by the mold bending or contracting when pressure is applied. The material of the flexible mold is also not particularly limited as long as pressure is transmitted to the material filled inside the mold in the pressurizing step described later and a molded body is formed, but examples include silicone resin, rubber, pulp, polyethylene terephthalate, aluminum, stainless steel, etc., or combinations thereof. The volume of the mold (for example, when using molds 2 and 2', the sum of the volumes of mold 2 and mold 2') is not particularly limited, but can be set in the range of 0.01 to 1000 mL, preferably 0.1 to 200 mL, and more preferably 0.2 to 100 mL. The powder material can be filled into the mold by combining mold 2 filled with material powder 1 and mold 2' filled with material powder 1'. In this process, it is preferable that the mold be sealed so that the liquid in which the mold will be placed in a later step does not enter the mold. Alternatively, the powder material and the liquid can be prevented from coming into contact by placing the entire mold filled with the powder material into another container (such as a bag) and reducing the pressure (so-called vacuum packing).

[0019] In the method of the present invention, the next step is to place a mold filled with the powder material containing the extracellular matrix powder into a liquid. The liquid in which the mold filled with the powder material is placed is not particularly limited, but may include water, oil, alcohol, or a combination thereof.

[0020] In the method of the present invention, a step is performed to pressurize the liquid in which the mold is placed. The pressure in this pressurizing operation is not particularly limited, but can be appropriately set in the range of, for example, 1100 to 100,000,000 mbar, preferably 1500 to 500,000,000 mbar, and more preferably 2000 to 100,000,000 mbar. The temperature in the pressurizing operation is not particularly limited, but can be appropriately set in the range of, for example, 0 to 50°C, preferably 4 to 30°C, and more preferably 10 to 25°C. The time of the pressurizing operation is also not particularly limited, but can be appropriately set in the range of, for example, 1 to 100 minutes, preferably 2 to 50 minutes, and more preferably 3 to 30 minutes. In the present invention, as a method for obtaining a molded body by pressurizing a mold filled with the above material in a liquid, examples include Cold Isostatic Pressing (CIP). In addition, high hydrostatic pressure (HHP), which uses particularly high pressure for processing among CIP methods, can also be used. During the pressurization process, the liquid in the pressurized container, the mold placed in the liquid, and the material powder filled in the mold are pressurized, forming a molded body corresponding to the shape of the mold. The method of the present invention may also include a step of depressurization after the pressurization process. Furthermore, the method of the present invention may further include a step of removing the pressurized molded body of material powder from the mold.

[0021] Schematic diagrams of various embodiments of the method of the present invention are shown in Figure 3. First, a schematic diagram is shown of a method in which a molded body is obtained by performing the above pressurization step once, using a material powder containing extracellular matrix powder derived from one type of tissue. In the method shown in Figure 3(1), the material powder is pressurized while filled in a mold, but in order to make the composition of the filled material powder easier to understand, the mold is omitted in Figure 3(1) and the filled material powder is shown. Similarly in Figures 3(2) to (4), the mold is omitted and the filled material powder is shown, but in the methods described in these figures as well, the material powder is pressurized while filled in a mold. The material powder may contain extracellular matrix powder derived from one type of tissue as shown in Figure 3(1), but it may also contain extracellular matrix powder derived from two or more types of tissue as shown in Figure 3(2). Furthermore, in the method of the present invention, for example, it is possible not only to obtain a molded body by performing the above pressurization step once, but also, after obtaining a molded body by performing the above pressurization step once, to fill the molded body and another material powder into a mold, perform the pressurization step again, and obtain a molded body consisting of two layers: a core first layer and a second layer surrounding the first layer. A method for manufacturing such a molded body consisting of two layers is shown in Figure 3(3). By repeating these filling and pressurization steps, it is also possible to obtain a molded body with three or more layers (for example, three, four, five layers, etc.). In another embodiment, a porous molded body can also be obtained by pressurizing a material powder containing extracellular matrix powder and other powders (for example, NaCl), and then removing the powder that is not extracellular matrix powder (for example, NaCl). In this embodiment, the powder that is not extracellular matrix powder can be removed, for example, by immersing the molded body of the material powder containing extracellular matrix powder and other powders (for example, NaCl) in a buffer solution (such as phosphate buffer solution) and then freeze-drying it. An overview of such embodiments is shown in Figure 3(4), using NaCl as an example of a powder other than extracellular matrix powder.

[0022] By using the method of the present invention described above, pressure can be applied uniformly to the surface of the filled material, thereby ensuring uniform density of the material on the surface of the resulting molded body. Furthermore, by using the method of the present invention, a molded body with higher mechanical strength can be obtained compared to cases using a manual press, etc. Moreover, any shape can be created as the mold using a 3D printer or the like. Therefore, according to the method of the present invention, molded bodies derived from extracellular matrix of various shapes can be precisely manufactured while suppressing deformation of their shape.

[0023] Molded body The present invention provides molded articles derived from various extracellular matrix components. In one embodiment, the present invention provides a molded article derived from an extracellular matrix, which is formed by joining together a plurality of molded article portions containing extracellular matrix powder, wherein two or more of the plurality of molded article portions contain extracellular matrix powder derived from different types. In this embodiment, the molded article of the present invention is a joint of a plurality of (e.g., 2 to 5, 2 to 4, 2 to 3, 2, etc.) molded article portions. In this embodiment, each of the plurality of molded article portions constituting the molded article of the present invention contains extracellular matrix powder. In this embodiment, two or more of the plurality of molded article portions (e.g., 2 to 4, preferably 2 to 3, more preferably 2) contain extracellular matrix powder derived from different types. In this embodiment, the "two or more molded body portions containing extracellular matrix powders derived from different types of materials" are typically preferably not to have a common type of extracellular matrix powder (for example, a molded body portion having liver-derived extracellular matrix powder and another molded body portion having heart-derived extracellular matrix powder), but are not limited to this embodiment and may have a common type of extracellular matrix powder (for example, a molded body portion having a mixture of brain-derived extracellular matrix powder and liver-derived extracellular matrix powder and another molded body portion having a mixture of brain-derived extracellular matrix powder and heart-derived extracellular matrix powder). Furthermore, in this embodiment, as described above, if two or more molded body parts have a common type of extracellular matrix powder, for example, one molded body part has brain-derived extracellular matrix powder, and another molded body part has a mixture of brain-derived extracellular matrix powder and heart-derived extracellular matrix powder, so that one molded body part has the same type of tissue-derived extracellular matrix powder as the other molded body part, and the other molded body part has yet another type of tissue-derived extracellular matrix powder.

[0024] In these embodiments, with respect to the "two or more molded body portions containing extracellular matrix powders derived from different types" included in the molded body of the present invention, for example, if there are two molded body portions containing extracellular matrix powders derived from different types, the mass ratio is preferably 0.01 to 1 g, and more preferably 0.1 to 1 g, as the mass of the other molded body portion to the mass of 1 g of the mass of one molded body portion. Furthermore, in these embodiments, the proportion of the "two or more molded body portions containing extracellular matrix powders derived from different types" among the molded body portions included in the molded body of the present invention can be, for example, 90% or more, preferably 95% or more, and may be 100% of the total volume of the molded body.

[0025] In these embodiments, a molded body having two or more molded body portions containing extracellular matrix powders derived from different types can be obtained, for example, in the method for producing an extracellular matrix-derived molded body described above, by using a mold consisting of two molds, filling one mold with material powder containing extracellular matrix powder derived from one type of tissue, and filling the other mold with material powder containing extracellular matrix powder derived from another type of tissue. For example, in the case of Figure 1, by using material powder containing extracellular matrix powder derived from one type of tissue as material 1, and material powder containing extracellular matrix powder derived from a different type of tissue as material 1', a molded body containing extracellular matrix powder derived from different types of tissues in the upper and lower parts can be obtained. Alternatively, by filling one mold with material powder containing extracellular matrix powder derived from one type of tissue, and then filling it with material powder containing extracellular matrix powder derived from another type of tissue, and similarly filling the other mold with material powder containing extracellular matrix powder derived from one type of tissue and extracellular matrix powder derived from another type of tissue, a molded body containing extracellular matrix powder derived from different types of tissues in the lateral direction can be obtained.

[0026] In this embodiment, by including at least two extracellular matrix powders derived from different types in the molded body portion, there are advantages such as the reproduction of tissues including hard and soft tissues, the reproduction of tissues having a layered structure, and the creation of extracellular matrix materials in combinations not found in biological tissues.

[0027] As mentioned above, when material powder containing extracellular matrix powder is molded using a conventional compression molding machine, the material powder is compressed from above and below, resulting in a higher density at the top and bottom of the resulting molded body and a relatively lower density at the sides. Therefore, the molded body has a large rate of change in surface density. In contrast, according to the method for manufacturing an extracellular matrix-derived molded body of the present invention described above, pressure is applied to the mold filled with material powder from all directions, making it possible to obtain a molded body with a uniform surface density.

[0028] Furthermore, as mentioned above, when material powder containing extracellular matrix powder is molded using a conventional compression molding machine, pressure is applied in the vertical direction of the molded body, making it possible to form irregularities on the upper and lower surfaces of the molded body. However, when molding using a conventional compression molding machine, the pressure applied in the lateral direction of the molded body is weak, making it difficult to form irregularities in the lateral direction of the molded body. Even if irregularities are formed in the lateral direction, they become brittle because sufficient pressure is not applied to them. In contrast, according to the method for manufacturing an extracellular matrix-derived molded body of the present invention described above, pressure is applied from all directions to the mold filled with material powder, making it possible to form irregularities in the lateral direction of the molded body. Therefore, the present invention provides a molded body made by pressing extracellular matrix powder with two molds, wherein the molded body has irregularities on surfaces other than the horizontal plane relative to the two molds. In this embodiment, the horizontal planes for the two molds refer to the plane that is parallel or approximately parallel to the plane containing the line formed by connecting the points where the two molds touch (or, if the line formed by connecting the points where the two molds touch does not lie on a plane, to the plane that encloses the line formed by connecting the points where the two molds touch, such that the distance between the two planes is shortest). For example, in Figure 1, this refers to the top and bottom surfaces of the star shape.

[0029] Furthermore, when material powder containing extracellular matrix powder is molded using a conventional compression molding machine, the material powder is compressed from above and below. As a result, the resulting molded body exhibits relatively lower mechanical strength (elastic modulus) when pressed on the sides compared to the mechanical strength (elastic modulus) when pressed in the vertical direction. In contrast, according to the method for producing an extracellular matrix-derived molded body of the present invention described above, pressure is applied to the mold filled with material powder from all directions. Therefore, high values ​​can be obtained not only for mechanical strength (elastic modulus) when pressed in the vertical direction but also for mechanical strength when pressed on the sides. Accordingly, in one embodiment, the present invention provides a molded body in which the elastic modulus when pressed in the linear direction included in the horizontal plane of two molds is higher than that of a molded body of the same shape obtained using a conventional two-way compression molding machine, for example, 5% or more, 10% or more, preferably 20% or more, and more preferably 30% or more higher. "Obtained using a conventional two-way compression molding machine" means a molded body obtained by applying the same amount of pressure as that used to form the molded body of the present invention using a conventional two-way compression molding machine. If the ratio of the above elastic modulus differs depending on the direction of the straight lines included in the horizontal plane for the two molds, the elastic modulus measured by applying pressure in the direction that minimizes the difference in elastic modulus between the conventional compression molding method and the method of the present invention can be adopted. The upper limit of the above difference in elastic modulus is not limited, but can be selected from, for example, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, 100% or less, etc. The elastic modulus can be measured using a method used in the art to which the present invention belongs, for example, based on the method for measuring the flexural modulus specified in JIS K 7171:2016. In another embodiment, the present invention provides a molded body in which the hardness when pressed in the straight line direction included in the horizontal plane for the two molds is harder than a molded body of the same shape obtained using a conventional two-way compression molding machine, for example, a molded body that is 5% or more, 10% or more, preferably 20% or more, and more preferably 30% or more hard.If the ratio of hardness differs depending on the orientation of the straight lines included in the horizontal plane for the two molds, the hardness measured by applying pressure in the direction that minimizes the difference in hardness between the conventional compression molding method and the method of the present invention can be adopted. The upper limit of the above hardness difference is not limited, but can be selected from, for example, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, 100% or less, etc. In this embodiment, hardness can be measured based on methods used in the art to which the present invention belongs, for example, an indentation test specified in JIS K7215, JIS 6253-.3, etc.

[0030] The following examples illustrate specific embodiments of the present invention, but the present invention is not limited to the following embodiments. [Examples]

[0031] Example 1 1. Preparation of decellularized tissue powder Brains, spinal cords, livers, cartilage, and bone marrows of research pigs were collected and washed with physiological saline. After washing, the brain tissue was placed in polyethylene bags with physiological saline and sealed. High-pressure hydrostatic treatment was performed at 10,000 atm using a Dr. Chef machine (Kobe Steel). After high-pressure hydrostatic treatment, the brain tissue was washed with a nuclease-degrading enzyme-containing washing solution and an alcohol-containing washing solution. After washing, each decellularized tissue was freeze-dried using a freeze-dryer (Christo). The freeze-dried decellularized brain tissue was pulverized using a mill, food processor, tube-type dry grinder (IKA), agate grinder (AS ONE), etc., and used as decellularized brain powder. Decellularized tissue powders of spinal cord, liver, cartilage, or bone marrow were obtained in the same manner as above, except that washed spinal cord, liver, cartilage, or bone marrow was used instead of washed brain tissue.

[0032] 2. Preparation of decellularized brain powder blocks by CIP molding Decellularized brain powder in a silicone resin mold (approximately 1.6 cm in volume) as shown in Figure 4. 3The mixture was filled into a silicone resin mold, which was then placed in a nylon poly bag and vacuum-packed. A CIP treatment was performed in water at 2,000 atm using a Dr. Chef (manufactured by Kobe Steel). After the CIP treatment, a cylindrical decellularized tissue powder block was removed from the silicone resin mold. A photograph of the resulting molded body is shown in Figure 4.

[0033] Example 2 1. Preparation of a mixed block of decellularized brain powder and hyaluronic acid. Decellularized tissue powder and hyaluronic acid (Fujifilm Wako) were mixed in a mass ratio of 9:1, filled into the same silicone resin mold as in Example 1, and sealed in a nylon poly bag. CIP treatment was performed at 2,000 atm using Dr. Chef (Kobe Steel). After CIP treatment, the decellularized tissue powder block was removed from the silicone mold, and a mixed molded body of decellularized brain powder and hyaluronic acid was prepared. A photograph of the obtained molded body is shown in Figure 5.

[0034] Example 3 1. Preparation of a composite block of decellularized brain powder and decellularized liver powder. Figure 6 shows a photograph of a flower-shaped silicone resin mold (volume approximately 0.2 cm²). 3 Decellularized brain powder and decellularized liver powder were alternately filled into the petals of the flower, and the mixture was sealed in a nylon poly bag. Using a Dr. Chef (manufactured by Kobe Steel, Ltd.), a composite block was fabricated by CIP treatment at 2,000 atm. A photograph of the resulting molded body is shown in Figure 6.

[0035] 2. Preparation of a composite block of decellularized spinal cord powder and decellularized liver powder. Figure 7 shows a photograph of the lower part of a pig-shaped silicone resin mold (volume (lower part) approximately 2.0 cm²). 3 Decellularized spinal cord powder is filled into the upper part of the silicone resin mold (volume (upper part) approximately 1.6 cm). 3 Decellularized liver powder was filled into the container and sealed in a nylon poly bag. Using a Dr. Chef (manufactured by Kobe Steel, Ltd.), a CIP treatment was performed at 2,000 atm to produce a composite block. A photograph of the resulting molded body is shown in Figure 7.

[0036] Example 4 1. Preparation of a two-layer block consisting of decellularized bone marrow powder and decellularized cartilage powder. Decellularized bone marrow powder was filled into a cylindrical silicone mold with a diameter of 6 mm and a height of 3 mm, and sealed in a nylon poly bag. Using a Dr. Chef (manufactured by Kobe Steel, Ltd.), CIP treatment was performed at 2,000 atm to produce a decellularized bone marrow block. Decellularized cartilage powder was placed in a silicone mold with a diameter of 8 mm and a height of 5 mm, and the decellularized bone marrow block was placed on top of the powder. Furthermore, decellularized cartilage powder was filled between the decellularized bone marrow block and the silicone mold, and CIP treatment was performed at 2,000 to 10,000 atm to produce a two-layer block. A photograph of the obtained molded body is shown in Figure 8.

[0037] Example 5 1. Preparation of porous decellularized bone marrow blocks Decellularized bone marrow powder mixed with 0-90% NaCl was filled into a cylindrical silicone mold with a diameter of 10 mm and a height of 5 mm. Using a Dr. Chef (manufactured by Kobe Steel, Inc.), a CIP treatment was performed at 2,000 atm to produce a NaCl-containing decellularized bone marrow block. The NaCl-containing decellularized bone marrow powder block was immersed in phosphate buffer to remove the NaCl, and then freeze-dried to produce a porous decellularized bone marrow block.

[0038] The outline and results of the experiment are shown in Figure 9. Porosity was confirmed by observing the prepared decellularized bone marrow blocks and porous decellularized bone marrow blocks using SEM (Shinshu University Instrumental Analysis Support Division, Ueda Branch). No pores were observed in the decellularized bone marrow blocks without NaCl mixing, but pores were observed on the surface and in cross-section of the porous decellularized bone marrow blocks mixed with 60% NaCl. [Industrial applicability]

[0039] According to the method of the present invention, molded bodies of any shape can be manufactured as extracellular matrix-derived molded bodies. Therefore, for example, when the root of a tooth is extracted, a silicone mold can be created from X-ray data to manufacture an extracellular matrix-derived molded body, and by using this molded body as a scaffold for cell transplantation, tissue regeneration can be performed to match the shape of the extracted area. It can also be useful as an inducer for bone regeneration when the jawbone or skull is fractured. Furthermore, it is possible to create molded bodies for the regeneration of other tissues (such as skin) using the extracellular matrix of tissues with high regenerative capacity, such as the liver. In addition to being used as instruments for treatment such as cell transplantation, the molded bodies of the present invention are also useful as equipment for cell culture. Extracellular matrix-derived molded bodies enable the treatment of damaged areas with shapes that do not exist in the tissue of the extracellular matrix raw material. In the regeneration of three-dimensional tissue using scaffold materials, angiogenesis within the material is important, and by using an extracellular matrix molded body containing powder with vascular induction ability, it is possible to provide a material with superior vascular induction ability compared to existing materials. Using the method of the present invention, it is possible to produce extracellular matrix-derived molded bodies that mimic tissues consisting of soft tissues and hard tissues, such as cartilage and bone, or tendons and bone.

Claims

1. A process of filling a mold with material powder containing extracellular matrix powder. The process of placing a mold filled with the material powder into a liquid. The process of pressurizing the liquid in which the mold is placed. A method for producing an extracellular matrix-derived molded article, including the above.

2. The method according to claim 1, wherein the extracellular matrix powder is a bio-derived powder.

3. The method according to claim 1 or 2, wherein the mold consists of at least one selected from the group consisting of silicone resin, rubber, pulp, polyethylene terephthalate, aluminum, and stainless steel.

4. A molded article derived from extracellular matrix, obtained by the method described in any one of claims 1 to 3.

5. A molded body made by pressing a material powder containing extracellular matrix powder with two molds, wherein the two molds have irregularities on surfaces other than the horizontal plane, and is obtained by the method according to any one of claims 1 to 3.

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