Method for producing three-dimensional shaped article and ink set for

Abstract

Provided are: a method for producing a three-dimensional molded article, which is capable of producing a three-dimensional molded article with good molding accuracy, even when producing a three-dimensional molded article having a complicated shape, for example, comprising a soft material; and an ink set for producing a three-dimensional molded article. The present invention relates to a method for producing a three-dimensionally shaped article, comprising: a step for discharging (a) an ink for a model material containing a photocrosslinkable polymer and (b) an ink for a support material containing a support material and a first crosslinking factor; a step for photocuring the discharged photocrosslinkable polymer; and a step for removing the molded object of the support material ink.

Description

Technical Field

[0001] The present invention relates to a method for manufacturing a three-dimensional object and an ink set for manufacturing a three-dimensional object, and in particular to a method for manufacturing a three-dimensional object of a complex shape made of soft materials in the field of regenerative medicine. Background Art

[0002] The technology of manufacturing three-dimensional objects using a modeling device called a three-dimensional printer has been studied in various fields with the goal of practical application. For example, in the field of regenerative medicine, in order to be used as artificial organs, it is required to manufacture three-dimensional objects with complex shapes and bridges or holes made of soft materials. When such three-dimensional objects are manufactured from bio-ink using a three-dimensional printer, the bio-ink will flow out (liquid dripping) and disintegrate before gelation, or deform due to gravity, so it is required to improve the modeling accuracy.

[0003] Patent document 1 discloses the following: With the goal of applying to fields such as regenerative medicine, by adding silk nanofibers to 3D printing system ink containing natural polymers and / or synthetic polymers, the viscosity is low when discharged from the nozzle, the pressure during discharge can be reduced, and the viscosity is high on the printed substrate, which can fully prevent the deformation of the modeled object. On the other hand, it is hoped to develop a new method for making three-dimensional models with a further expanded range of materials.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Publication No. 2020-156357 Summary of the invention

[0007] Problems to be solved by the invention

[0008] The object of the present invention is to provide a method for manufacturing a three-dimensional object and an ink set for manufacturing a three-dimensional object, which can manufacture a three-dimensional object with good modeling accuracy even when manufacturing a three-dimensional object of a complex shape, such as one made of soft materials.

[0009] Means for solving problems

[0010] The inventors of the present invention have conducted various studies and found that, when a model material ink containing a photocrosslinkable polymer and a support material ink containing a support material and a crosslinking factor are discharged separately, the discharged photocrosslinkable polymer is photocured, and the support material ink is removed to form a three-dimensional object, the three-dimensional object can be manufactured with good modeling accuracy even when making a three-dimensional object of a complex shape, such as one made of a soft material.

[0011] That is, the present invention (1) relates to a method for manufacturing a three-dimensional object, comprising:

[0012] A step of separately discharging (a) a model material ink containing a photo-crosslinkable polymer and (b) a support material ink containing a support material and a first crosslinking factor;

[0013] A step of photocuring the discharged photo-crosslinkable polymer; and

[0014] The process of removing the support material ink from the molded object.

[0015] The present invention (2) is the method for producing a three-dimensional object according to the present invention (1), wherein the model material ink (a) further contains a second cross-linking factor.

[0016] The present invention (3) is the method for producing a three-dimensional object according to the present invention (1) or (2), wherein the model material ink (a) contains substantially no photopolymerization initiator.

[0017] The present invention (4) is a method for producing a three-dimensional object according to any one of the present inventions (1) to (3), wherein the supporting material ink (b) does not substantially contain a photo-crosslinkable polymer or a photo-crosslinkable monomer.

[0018] The present invention (5) is the method for producing a three-dimensional object according to any one of the present inventions (1) to (4), wherein the supporting material ink (b) further contains a second cross-linking factor.

[0019] The present invention (6) is a method for producing a three-dimensional object according to any one of the present inventions (1) to (5), wherein the support material is a water-soluble polymer or a water-dispersible polymer.

[0020] The present invention (7) is a method for manufacturing a three-dimensional object described in the present invention (6), wherein the above-mentioned water-soluble polymer or water-dispersible polymer is a water-soluble polymer or water-dispersible polymer that forms an aqueous gel that agglomerates or reduces its viscosity when reacting with an ionic compound, and in the process of removing the object of the support material ink, the ionic compound is allowed to act to remove the above-mentioned support material ink (b) from the object.

[0021] The present invention (8) is an ink set for making a three-dimensional object, comprising:

[0022] (a) a model material ink comprising a photo-crosslinkable polymer; and

[0023] (b) A supporting material ink comprising a supporting material and a first cross-linking factor.

[0024] The present invention (9) is an ink set for making three-dimensional objects as described in the present invention (8), wherein the supporting material ink (b) contains a water-soluble polymer or a water-dispersible polymer that forms an aqueous gel that agglomerates or reduces viscosity by reacting with ionic compounds.

[0025] Effects of the Invention

[0026] According to the present invention, even when manufacturing a three-dimensional object having a complicated shape, for example, made of a soft material, the three-dimensional object can be manufactured with good molding accuracy by light irradiation. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a schematic diagram for explaining the process of manufacturing a three-dimensional object having a bridge portion by the method for manufacturing a three-dimensional object of the present invention.

[0028] Figure 2 Graph showing the viscosity of the supporting material ink produced in Production Example 2 with respect to the shear rate.

[0029] Figure 3 This is a photograph showing how a white precipitate is generated when Projelly (gel for ultrasonic inspection) used in Production Example 2 is allowed to react with an ionic compound.

[0030] Figure 4 The Projelly used in Production Example 2 was mixed with DMEM medium (Double's Modified Eagle's Medium), and cells were grown and cell growth was observed.

[0031] Figure 5 These are photographs of the three-dimensional objects produced in Example 1 and Comparative Example 1.

[0032] Figure 6 These are photographs of three-dimensional objects produced in Example 2 and Comparative Examples 2 to 3.

[0033] Figure 7 This is a photograph of the three-dimensional object produced in Example 3.

[0034] Figure 8 This is a photograph of the three-dimensional object produced in Example 4.

[0035] Fig. 9 This is a photograph of the three-dimensional object produced in Example 5.

[0036] Fig.10 This is a photograph of the three-dimensional object produced and cultured in Example 6.

[0037] Fig.11This is a schematic diagram for explaining a step of further using a second supporting material ink to produce a three-dimensional object in the method for producing a three-dimensional object of the present invention.

[0038] Fig.12 It is used to illustrate Fig.11 A schematic diagram of another example of the process shown.

[0039] Fig.13 It is used to illustrate Fig.11 A schematic diagram of another example of the process shown. DETAILED DESCRIPTION

[0040] <<Method for producing three-dimensional object>>

[0041] The method for manufacturing a three-dimensional shaped object of the present invention is characterized in that it includes: a process of separately discharging (a) a model material ink containing a photocrosslinkable polymer and (b) a support material ink containing a support material and a first crosslinking factor; a process of photocuring the discharged photocrosslinkable polymer; and a process of removing the shaped object from the support material ink.

[0042] Below, refer to Figure 1 The method for producing a three-dimensional object of the present invention will be briefly described. Figure 1 This is a schematic diagram for explaining the process of manufacturing a three-dimensional object having a bridge portion by the method for manufacturing a three-dimensional object of the present invention. Figure 1 (a) schematically shows a state where the supporting material ink 1 is discharged from a nozzle 3a of a 3D printer. Figure 1 (b) schematically shows the discharge of model material ink 2 from nozzle 3b of a 3D printer. It should be noted that nozzle 3a and nozzle 3b may be the same nozzle, but are preferably different nozzles. Here, support material ink 1 may be discharged, and then model material ink 2 may be discharged at a position surrounded by support material ink 1 to form a layer, and this operation may be repeated to form a layered structure.

[0043] like Figure 1 (a) and Figure 1 As shown in (b), the discharged support material ink 1 contacts the discharged model material ink 2. For example, when the support material ink 1 contains a support material and a first cross-linking factor, the first cross-linking factor is supplied from the discharged support material ink 1 to the discharged model material ink 2, and the photo-cross-linkable polymer in the discharged model material ink 2 is cross-linked by light, thereby gelling the model material ink 2. Figure 1(c) shows the following process: after the gelation of the model material ink 2 is completed, the obtained object is immersed in a solution 5 for removing the object of the support material ink 1 to remove the object of the support material ink 1. By removing the object of the support material ink 1, a three-dimensional object 2A (object of the model material ink) having a complex shape with a bridge portion 2a or a hole 2b can also be produced.

[0044] In the method for manufacturing a three-dimensional object of the present invention, it is also possible to discharge model material ink and support material ink into cylindrical containers such as beakers and culture dishes, square tube-shaped containers, and containers of other various shapes to make a three-dimensional object. The inner wall of the container becomes a support for the model material ink and / or the support material ink, so a higher-height modeling object can be made. It should be noted that the material of the container is not particularly limited as long as it becomes a material that becomes a support for the model material ink and / or the support material ink, and a container made of glass, resin, etc. can be used. In addition, the container can also be manufactured by three-dimensional modeling.

[0045] <Step of Separately Discharging (a) Model Material Ink Containing a Photo-crosslinkable Polymer and (b) Support Material Ink Containing a Support Material and a First Crosslinking Factor>

[0046] In the discharge process, for example, the model material ink (a) and the support material ink (b) containing the support material and the first cross-linking factor are discharged from the nozzle of the 3D printer to the target part such as on the substrate. When a 3D printer is used in the ink discharge process, the 3D printer is not particularly limited and can be any one of inkjet, laser, extrusion, etc., preferably an extrusion 3D printer. The nozzle for discharging the model material ink (a) is preferably different from the nozzle for discharging the support material ink (b).

[0047] ((a) Model material ink containing photo-crosslinkable polymer)

[0048] The model material ink (a) contains a photo-crosslinkable polymer, which is crosslinked by the first crosslinking factor contained in the support material ink under the action of light, thereby becoming a gel. The photo-crosslinkable polymer is not particularly limited, and examples thereof include polymers obtained by combining a polymer substrate with a compound having a phenolic hydroxyl group, polymers having a (meth)acrylate group such as gelatin methacrylate, amino-containing polysaccharides, polyphenols, etc. In the case where the polymer substrate has a photo-crosslinkable functional group, it can be used directly as a photo-crosslinkable polymer, or it can be further combined with a compound having a phenolic hydroxyl group and the like to introduce a photo-crosslinkable functional group for use.

[0049] The polymer substrate is not particularly limited, and examples thereof include polysaccharides, nucleic acids, carbohydrates, proteins, polypeptides, poly(α-hydroxy acids), polylactones, polyamino acids, polyanhydrides, polyorthoesters, polyanhydride-imide copolymers (poly(anhydride-co-imides)), polyorthocarbonates, poly(α-hydroxyalkanoates), polydioxanone, polyphosphates, polylactic acid, poly(L-lactide) (PLLA), poly(D,L-lactide) (PDLLA), polyglycolic acid, polyglycolide (PGA), polyglycolide (PLGA), L-lactide-D,L-lactide copolymers, D,L-lactide-trimethylene carbonate copolymers, Polyhydroxybutyrate (PHB), poly(ε-caprolactone), poly(δ-valerolactone), poly(γ-butyrolactone), polycaprolactone, poly(meth)acrylic acid, polycarboxylic acid, polyallylamine hydrochloride, polydiallyldimethylammonium chloride, polyalkyleneimines such as polyethyleneimine, polypropylene fumarate, polyvinyl alcohol, polyvinylpyrrolidone, polyolefins such as polyethylene (polyalkylenes), polymethyl methacrylate, carbon fiber, polyalkylene glycols such as polyethylene glycol, polyalkylene oxides such as polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-polypropylene oxide block copolymers, poly(ethylene terephthalate) polyamide, salts of these polymer substrates, etc.

[0050] Examples of polysaccharides include cellulose, hemicellulose, dextran, hyaluronic acid, chitin, chitosan, alginic acid, chondroitin sulfate, starch, pullulan, carrageenan, curdlan, fucoidan, amylose, amylopectin, pectin, salts thereof such as alkali metal salts, derivatives thereof, etc. Examples of polysaccharide derivatives include carboxymethylcellulose, methylcellulose, deacetylated chitins, deacetylated chitosans, etc.

[0051] Examples of proteins include simple proteins such as albumin, globulin, prolamin, gluten, histone, protamine, and sclerostin; complex proteins such as nucleoprotein, glycoprotein, chromoprotein, and phosphoprotein; gelatin, Proteins derived from peptone, etc.

[0052] The salt in the salt of the polymer substrate is not particularly limited, and examples thereof include acid addition salts, metal salts, ammonium salts, organic amine salts, and the like. Examples of acid addition salts include inorganic acid salts such as hydrochlorides, sulfates, and phosphates; organic acid salts such as acetates, maleates, fumarates, tartrates, and citrates. Examples of metal salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts, magnesium salts, aluminum salts, and zinc salts. Examples of organic amine salts include salts of morpholine, piperidine, and the like.

[0053] As the polymer substrate, polysaccharides and proteins are preferred because they are easy to supply and the resulting three-dimensional objects have good properties, and polysaccharides are more preferred. The polymer substrate may be used alone or in combination of two or more.

[0054] The compound having a phenolic hydroxyl group is not particularly limited, but is preferably a compound of the following general formula (1):

[0055] [Chemistry 1]

[0056]

[0057] (Where X 1 represents a hydroxyl group, an amino group or a carboxylate group. 2 ~X 6 One or two of them represent hydroxyl groups, and the rest represent hydrogen atoms or alkoxy groups having 1 to 6 carbon atoms. 2 ~X 6 When two of the hydroxyl groups represent hydroxyl groups, it is preferred that the two hydroxyl groups are in an ortho or para position. R represents a divalent hydrocarbon group having 1 to 10 carbon atoms which may or may not have a substituent. The crosslinkable polymer formed by introducing a phenolic hydroxyl group into a polymer substrate is easily crosslinked by exposure in the presence of a photoredox catalyst and a polymerization initiator, or a photopolymerization initiator. From the perspective of easily introducing a phenolic hydroxyl group into a polymer substrate, X 1 Preferably, a carboxylic acid (salt) group or an amino group is used, and an amino group is more preferred. It should be noted that the amino group is preferably a primary amino group or a secondary amino group. As the carboxylic acid (salt) group, a carboxylic acid group, an alkali metal salt of a carboxylic acid group, or an alkaline earth metal salt is preferred. In addition, the number of carbon atoms of the divalent hydrocarbon group represented by R is preferably 1 to 8, and more preferably 1 to 6. The divalent hydrocarbon group represented by R is not particularly limited, and examples thereof include alkylene groups, alkyl alkylene groups, and the like. In addition, examples of substituents that R may have include, for example, amide groups, ester groups, ether groups, and the like. It should be noted that X 1 In the case of a hydroxyl group, it is an alcoholic hydroxyl group.

[0058] Examples of the compound having a phenolic hydroxyl group include compounds having one phenolic hydroxyl group such as tyramine, homovanillic acid, and derivatives thereof; and compounds having two phenolic hydroxyl groups such as catecholamines such as dopamine, norepinephrine, and epinephrine. Among these, compounds having one phenolic hydroxyl group are preferred from the perspective of the crosslinking reactivity of the resulting crosslinkable polymer, and tyramine and tyramine derivatives are more preferred.

[0059] As the compound having a phenolic hydroxyl group, a commercially available product may be used, and examples of the commercially available product include tyramine hydrochloride (4-(2-aminoethyl)phenol hydrochloride, product number: T2879, manufactured by Sigma-Aldrich Co.).

[0060] The method for combining the polymer substrate with the compound having a phenolic hydroxyl group is not particularly limited, and examples include: a method of using a condensation agent to condense functional groups such as carboxyl, amino or alcoholic hydroxyl groups that the compound having a phenolic hydroxyl group may have with functional groups such as amino, carboxyl or thiol groups that the polymer substrate may have; a method of using glutamyl transferase for condensation; etc.

[0061] The condensing agent is not particularly limited, and examples thereof include 1,1-carbonyldiimidazole, dicyclohexylcarbodiimide, 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide hydrochloride (water-soluble carbodiimide: WSCD·HCl), etc. In the method of condensing the polymer substrate and the compound having a phenolic hydroxyl group using a condensing agent, and the method of condensing using glutamyl transferase, the pH, the concentration of the polymer substrate, the reaction temperature, the solvent, etc. can be appropriately selected according to the properties of the polymer substrate, the compound having a phenolic hydroxyl group, the condensing agent, or the glutamyl transferase used.

[0062] The introduction rate (modification rate) of the compound having a phenolic hydroxyl group into the polymer substrate is the ratio of the (modified) condensation reaction groups that have undergone condensation reaction among all the condensation reaction groups possessed by the polymer substrate. From the aspect of balancing the gelation speed and hardness (not too hard), it is preferably 0.3 mol% to 20 mol%, and more preferably 1 mol% to 10 mol% relative to 100 mol% of the condensation reaction groups possessed by the polymer substrate.

[0063] As the photo-crosslinkable polymer, amino-containing polysaccharides and polyphenols may also be used. Examples of amino-containing polysaccharides include acetylated chitin and chitosan. In addition, examples of polyphenols include catechin compounds, anthocyanidin compounds, rutin, and natural pigments.

[0064] Gelatin methacrylate (methacryloyl gelatin) is a substance in which a methacryloyl group is introduced into the side chain of gelatin, and its aqueous solution forms a gel when irradiated with light of a wavelength suitable for the photopolymerization initiator in the presence of the photopolymerization initiator.

[0065] The concentration of the photocrosslinkable polymer in the model material ink (a) is generally 0.1% to 30% by weight, preferably 0.5% to 20% by weight, and more preferably 0.75% to 10% by weight. If the concentration of the photocrosslinkable polymer is less than 0.1% by weight, the strength of the three-dimensional model may become insufficient. If it exceeds 30% by weight, the viscosity of the model material ink becomes too high, and the pressure when discharged from the nozzle becomes high, which may affect the material of the model material ink (a). In addition, the concentration of the crosslinkable polymer in the model material ink (a) is generally 0.1 to 30 w / v% (g / 100mL), preferably 0.5 to 20 w / v% (g / 100mL), and more preferably 0.75 to 10 w / v% (g / 100mL).

[0066] In the manufacturing method of the present invention, the model material ink (a) further includes a second crosslinking factor. The second crosslinking factor is a component that participates in the crosslinking of the photo-crosslinkable polymer together with the first crosslinking factor included in the support material ink, but does not crosslink the photo-crosslinkable polymer when alone, and is, for example, a photoredox catalyst. Specifically, ruthenium complexes such as tris(2,2'-bipyridine)dichlororuthenium(II) and iridium complexes such as tris(2-phenylpyridine)iridium(III) can be cited.

[0067] The content of the second crosslinking factor in the model material ink (a) is preferably 0.1 to 50 parts by weight, more preferably 1 to 30 parts by weight, relative to 100 parts by weight of the photo-crosslinkable polymer. In addition, the concentration of the second crosslinking factor in the model material ink (a) is not particularly limited, but is preferably 0.01 mM or more and 1 M or less. The concentration is more preferably 0.1 mM or more, further preferably 1 mM or more, and particularly preferably 5 mM or more.

[0068] The model material ink (a) preferably contains substantially no photopolymerization initiator, so that the photo-crosslinkable polymer does not undergo photo-crosslinking in the absence of the support material ink (b). The content of the photopolymerization initiator in the model material ink (a) is preferably 1% by mass or less, more preferably 0.5% by mass or less, and further preferably 0% by mass.

[0069] In addition to the photo-crosslinkable polymer and the second crosslinking factor, the model material ink (a) may also contain other components. As other components, various cells, solvents, chain transfer agents, plasticizers, pH adjusters, buffers, preservatives, solvents, ultraviolet absorbers, colorants, surfactants, etc. can be cited. As solvents, for example, water, phosphate buffered saline (PBS), a mixture of water and an organic solvent, etc. can be cited. As organic solvents, there are no particular restrictions, and for example, ethanol, glycerol, dimethyl sulfoxide, etc. can be cited.

[0070] As the source animal of the cell, mammals, birds, reptiles, etc. can be mentioned, preferably mammals. As mammals, humans, pigs, cattle, sheep, goats, rabbits, mice, rats, dogs, cats, chickens, etc. can be mentioned, preferably humans. As the cell type, epithelial cells, fibroblasts, chondrocytes, osteoblasts, smooth muscle cells, neural cells, stem cells, etc. can be mentioned.

[0071] The concentration of cells in the model material ink is not particularly limited, but is preferably 1×10 3 Cells / mL~1×10 9 cells / mL, more preferably 1×10 4 Cells / mL~1×10 7 cells / mL.

[0072] The model material ink (a) is preferably in liquid form at room temperature. By being in liquid form at room temperature, it can be easily discharged using a 3D printer or the like. The viscosity of the model material ink (a) at 20°C is not particularly limited, and is preferably 10 mPa·s or more, more preferably 20 mPa·s or more, and further preferably 50 mPa·s or more. In addition, the above-mentioned viscosity is preferably 100000 mPa·s or less, more preferably 10000 mPa·s or less, and further preferably 2000 mPa·s or less. The manufacturing method of the present invention can fully prevent the outflow (liquid sagging) of the model material ink (a) before gelation, so that a low-viscosity model material ink (a) can be appropriately used. It should be noted that the above-mentioned viscosity is measured using a cone-plate E-type viscometer at a rotation speed of 20 rpm.

[0073] The model material ink (a) can be produced by mixing the above-mentioned photo-crosslinkable polymer, the second crosslinking factor, and other components used as necessary.

[0074] ((b) Support material ink comprising a support material and a first cross-linking factor)

[0075] The support material ink (b) can be formed into a modeled object by maintaining its shape through cross-linking after being discharged, but an ink that can maintain its shape and directly form a modeled object is preferred because of its simplicity. The modeled object of the support material ink (b) maintains the shape of the model material ink (a) until the model material ink (a) is fully gelled, thereby preventing the model material ink (a) from flowing out (liquid dripping) and deformation of the model material ink (a) due to gravity. After the model material ink (a) is gelled, the modeled object of the support material ink (b) is removed by the method described below.

[0076] The support material contained in the support material ink (b) is a natural polymer, a synthetic polymer or other polymer, and as the polymer, for example, polysaccharides, nucleic acids, carbohydrates, proteins, polypeptides, polyamino acids, polylactic acid, polyalkylene oxides such as polyethylene oxide, polyalkylene imines such as polyethylene imine, polyvinyl pyrrolidone, polyalkylene glycols such as polyethylene glycol, polyacrylic acid, polymethacrylic acid, polyglutamic acid, carboxyvinyl polymers, carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, albumin, gelatin, collagen, silk fibroin, polyvinyl alcohol, salts of these polymers, etc. As the above-mentioned polymer, polysaccharides, nucleic acids, carbohydrates, proteins, polypeptides, polyamino acids, polylactic acid, polyethylene oxide, polyethylene imine, polyvinyl pyrrolidone, polyethylene glycol, polyacrylic acid, polyglutamic acid, albumin, gelatin, collagen, polyvinyl alcohol, salts of these polymers are preferred. The salts in the salts of polysaccharides, proteins, and polymers are the same as the salts in the salts of polysaccharides, proteins, and polymer base materials described above. In addition, the above-mentioned support material can be a material obtained by cross-linking the above-mentioned polymer using a cross-linking agent. The support material preferably does not solidify under light irradiation. Specifically, it is preferred that it does not contain photo-crosslinkable polymers or photo-crosslinkable monomers.

[0077] Examples of the polysaccharides include cellulose, hemicellulose, dextran, hyaluronic acid, chitin, chitosan, alginic acid, chondroitin sulfate, starch, pullulan, carrageenan, curdlan, fucoidan, amylose, amylopectin, pectin, and salts thereof such as alkali metal salts, and derivatives thereof.

[0078] The supporting material is preferably a water-soluble polymer or a water-dispersible polymer. As a result, as described later, in the process of removing the shaped object of the supporting material ink (b), the shaped object can be easily removed under mild conditions using water or an aqueous solution. Here, in this specification, the solubility of the water-soluble polymer in 100 g of water at 20° C. is not particularly limited, but is preferably 1 g or more, and more preferably 5 g or more.

[0079] The water-soluble polymer or water-dispersible polymer forms a polymer aqueous gel, and the formed polymer aqueous gel is preferably a polymer aqueous gel that condenses or has a reduced viscosity by the action of an ionic compound. The water-soluble polymer or water-dispersible polymer that forms a polymer aqueous gel that condenses or has a reduced viscosity by the action of an ionic compound can include a polymer having a hydrocarbon chain (such as polyacrylic acid) having an acid group such as a carboxylic acid group as the main chain and cross-linked by a cross-linking agent. The cross-linking agent is not particularly limited, and can include allyl sucrose, pentaerythritol, etc. Ionic compounds are described below.

[0080] From the perspective of further improving the pseudoplasticity of the support material ink (b), the concentration of the polymer in the support material ink (b) is preferably 0.1% by weight or more, more preferably 0.3% by weight or more, more preferably 0.5% by weight or more, and particularly preferably 1.0% by weight or more. In addition, the concentration of the polymer is preferably 30.0% by weight or less, more preferably 15.0% by weight or less, and even more preferably 10.0% by weight or less. It should be noted that when the support material ink (b) contains two or more polymers, the above concentration refers to the total concentration of all polymers contained in the support material ink.

[0081] The support material ink (b) further includes a first crosslinking factor. The first crosslinking factor refers to a component that participates in the crosslinking of the photo-crosslinkable polymer alone or together with a second crosslinking factor included in the model material ink and / or the support material ink, such as a polymerization initiator. Specifically, polymerization initiators such as sodium persulfate (SPS), lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP), 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, and 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone can be cited.

[0082] The content of the first cross-linking factor is preferably 0.1 to 50 parts by weight, more preferably 0.5 to 30 parts by weight, relative to 100 parts by weight of the photo-cross-linkable polymer. In addition, the concentration of the first cross-linking factor in the support material ink (b) is not particularly limited, but is preferably 0.01 mM or more and 1 M or less. The concentration is more preferably 0.1 mM or more, further preferably 1 mM or more, and particularly preferably 5 mM or more.

[0083] The supporting material ink (b) preferably further contains a second cross-linking factor. Specific examples of the second cross-linking factor are as described above.

[0084] The content of the second crosslinking factor in the support material ink (b) is preferably 0.1 to 50 parts by weight, more preferably 1 to 30 parts by weight, relative to 100 parts by weight of the photo-crosslinkable polymer. In addition, the concentration of the second crosslinking factor in the support material ink (b) is not particularly limited, but is preferably 0.01 mM or more and 1 M or less. The concentration is more preferably 0.1 mM or more, further preferably 1 mM or more, and particularly preferably 5 mM or more.

[0085] In order to facilitate the removal of the shaped object of the support material ink, the support material ink (b) preferably does not substantially contain a photo-crosslinkable polymer or a photo-crosslinkable monomer so that the support material ink alone does not undergo photo-crosslinking. The content of the photo-crosslinkable polymer or the photo-crosslinkable monomer in the support material ink (b) is preferably 1% by mass or less, more preferably 0.1% by mass or less, and further preferably 0% by mass.

[0086] In addition to the polymer and the first cross-linking factor as the supporting material, the supporting material ink (b) may also contain other components. As other components, humectants such as glycerol, alkali metal hydroxides, pH adjusters such as organic amines, preservatives, colorants, solvents, plasticizers, ultraviolet absorbers, surfactants, etc. can be cited. As solvents, for example, water, phosphate buffered saline (PBS), a mixture of water and an organic solvent, etc. can be cited. As organic solvents, there are no particular restrictions, and for example, ethanol, glycerol, etc. can be cited.

[0087] The ink (b) for supporting material is preferably in liquid or gel form at room temperature, more preferably in gel form. By being in gel form at room temperature, it can be easily molded using a 3D printer or the like. The viscosity of the ink (b) for supporting material at 20°C and a shear rate of 0.01 (1 / s) is preferably 10000 mPa·s or more, and from the perspective of being able to maintain its own shape, it is more preferably 100000 mPa·s or more, and further preferably 500000 mPa·s or more. In addition, the upper limit of the viscosity is not particularly limited, and is usually 10000000 mPa·s or less.

[0088] The viscosity of the support material ink (b) at 20°C and a shear rate of 10 (1 / s) is preferably 10 mPa·s or more, more preferably 100 mPa·s or more, and further preferably 1000 mPa·s or more. In addition, the upper limit of the viscosity is not particularly limited, but is usually less than 10000 mPa·s. It should be noted that the above viscosity is a value measured using a viscosity / viscoelasticity measuring device manufactured by Thermo Fisher Scientific.

[0089] The ratio of the viscosity of the support material ink (b) at 20°C and a shear rate of 0.01 (1 / s) to the viscosity at a shear rate of 10 (1 / s) is preferably 5 or more, more preferably 10 or more, further preferably 20 or more, and particularly preferably 50 or more. As a result, the pseudoplasticity of the support material ink (b) becomes more excellent.

[0090] The supporting material ink (b) can be produced by mixing the polymer, the first cross-linking factor, and other components as required. The conditions for mixing are not particularly limited.

[0091] As described above, in the manufacturing method of the present invention, a three-dimensional printer is usually used to discharge the model material ink (a) and the support material ink (b) respectively to form layers, and this operation is repeated to perform layering. The discharged model material ink (a) is brought into contact with the discharged support material ink (b), and the discharged first cross-linking factor alone or together with the second cross-linking factor cross-links the photo-cross-linkable polymer, thereby molding a model of the model material ink (a). Here, the first cross-linking factor, or the first cross-linking factor and the second cross-linking factor contained in the discharged support material ink (b) are supplied to the discharged model material ink (a). It should be noted that in the manufacturing method of the present invention, in addition to the cross-linking of the photo-cross-linkable polymer caused by the first cross-linking factor, or the first cross-linking factor and the second cross-linking factor, ionic cross-linking, photo-cross-linking, enzyme cross-linking, temperature changes, etc. can also contribute to the cross-linking of the cross-linkable polymer.

[0092] (Ink for second supporting material including second supporting material)

[0093] In the manufacturing method of the present invention, the second supporting material ink can be discharged together with the model material ink (a) and the supporting material ink (b) (hereinafter also referred to as the first supporting material ink) as a supporting material for the model material ink and the first supporting material ink for manufacturing. The second supporting material ink can be discharged in advance to produce a three-dimensional object (container or outer frame), or only a part of the three-dimensional object (container or outer frame) can be produced and the remaining part can be discharged together with the model material ink and the first supporting material ink. In addition, all can be produced at the same time. The three-dimensional object (container or outer frame) made by the second supporting material ink becomes a support body for the model material ink and the first supporting material ink, so that the collapse of the model material ink and the first supporting material ink can be more fully prevented, and a three-dimensional object with a higher height can be produced as desired. In addition, such a second supporting material ink may not contain the first cross-linking factor. By replacing the first supporting material ink with such a second supporting material ink and reducing the discharge amount of the first supporting material ink, the amount of the first cross-linking factor contained in the first supporting material ink can also be saved. It should be noted that the second supporting material contained in the second supporting material ink is not particularly limited as long as it becomes a support body for the model material ink and / or the supporting material ink, and the supporting material used in the above-mentioned supporting material ink (b) or glass, resin, etc. can be used. In addition, as described later, the molded object of the second supporting material ink can be removed in the same manner as the molded object of the first supporting material ink by selecting an appropriate material. The model material ink may be partially or completely in contact with the molded object composed of the second supporting material.

[0094] Fig.11 Schematic diagram for explaining the process of further using a second supporting material ink to produce a three-dimensional object in the method for producing a three-dimensional object of the present invention. Figure 1 Different parts. Fig.11 (a) schematically shows a state where the second supporting material ink 11s is discharged from the nozzle 13a of the 3D printer. Fig.11 (b) schematically shows a state where the first supporting material ink 11 is discharged from the nozzle 13b of the three-dimensional printer. Fig.11 (c) schematically shows a state where the modeling material ink 12 is discharged from the nozzle 13c of the three-dimensional printer. It should be noted that the nozzle 13a, the nozzle 13b, and the nozzle 13c may be the same nozzle, but are preferably different from each other. Fig.11 In the process, the second supporting material ink 11s is discharged, the first supporting material ink 11 is discharged to the position surrounded by the second supporting material ink 11s, and the model material ink 12 is discharged to the position surrounded by the first supporting material ink 11, thereby forming one layer, and this operation is repeated to form a layered structure.

[0095] like Fig.11 (a)~ Fig.11 As shown in (c), the inner and outer peripheries of the discharged second supporting material ink 11s are both flat and thin-walled, and they are in contact with and support the discharged first supporting material ink 11, and also indirectly support the discharged modeling material ink 12. By using a material that can form a hard modeling object as the second supporting material ink 11s, it is possible to more fully prevent the modeling material ink 12 and the first supporting material ink 11 from collapsing during the gelation process, etc. In addition, a three-dimensional modeling object with a higher height can be produced as desired.

[0096] Fig.11 (d) and Figure 1 (c) similarly shows the following process: after the gelation of the model material ink 12 is completed, the obtained shaped object is immersed in a removing solution 15 to remove the shaped object of the first supporting material ink 11 and the shaped object of the second supporting material ink 11s. This process will be described below.

[0097] Fig.12 In addition to changing the discharge range of the first supporting material ink 21 and the second supporting material ink 21s to Figure 8 In addition to the Fig.11 The following only describes the Fig.11 Different parts. Fig.12 In the embodiment, the second supporting material ink is discharged in a manner that the inner peripheral portion becomes a step-like shape extending downward, and Fig.11By using a material that can form a hard modeling object and does not contain the first cross-linking factor as the second support material ink 21s, it is possible to more fully prevent the model material ink 22 and the first support material ink 21 from collapsing during the gelation process, etc., while reducing the discharge amount of the first support material ink 21, and saving the amount of the first cross-linking factor.

[0098] Fig.13 In addition to changing the discharge range of the second supporting material ink 31s to Fig.13 In addition to the Fig.12 The following only describes the Fig.12 Different parts. Fig.13 In the process, the second supporting material ink is discharged in a manner that the outer periphery is formed into a step-like shape that expands upward in accordance with the shape of the discharged model material ink 32 and the discharged first supporting material ink 31, and the second supporting material ink is discharged in a manner that the outer periphery is formed into a step-like shape that expands upward, and Fig.12 In comparison, the discharge amount of the second supporting material ink can also be reduced.

[0099] <Step of photocuring the discharged photo-crosslinkable polymer>

[0100] In the photocuring process, the first crosslinking factor, or the first crosslinking factor and the second crosslinking factor, which have migrated from the support material ink to the model material ink layer, react with the photocrosslinkable polymer by irradiation with light to cure. Examples of the light include visible light, ultraviolet light, X-rays, and electron beams.

[0101] <Step of Removing the Modeled Object from the Support Material Ink>

[0102] The removal process is not particularly limited as long as the object of the support material ink (b) is removed to obtain the object of the model material ink (a). For example, it is preferably carried out by immersing the object of the support material ink (b) in a solution for removing the object of the support material ink (b), and / or washing. From the perspective of reducing the influence on the object (three-dimensional object) of the model material ink (a), the removal process is preferably carried out under mild conditions, for example, preferably at a temperature of 10°C to 40°C. In addition, from the perspective of enzyme activity, the pH of the removal solution at 20°C is preferably 2 to 10, more preferably 5 to 9. It should be noted that the object of the support material ink is composed of the remaining components such as the support material (polymer) after the first cross-linking factor is supplied from the support material ink to the model material ink.

[0103] When the second supporting material ink is further used together with the supporting material ink (b), the shaped object of the supporting material ink (b) and the shaped object of the second supporting material ink can be removed by different methods respectively, but it is preferred to remove the shaped object of the second supporting material ink together with the shaped object of the supporting material ink (b) through the above-mentioned removal process.

[0104] When the supporting material is a water-soluble polymer or a water-dispersible polymer, water or an aqueous solution can be used as a removal solution. In addition, when the water-soluble polymer or the water-dispersible polymer forms a polymer aqueous gel, and the formed polymer aqueous gel acts on an ionic compound to condense or reduce viscosity, an aqueous solution of an ionic compound can be particularly preferably used as a removal solution. Regarding the action of the water-soluble polymer or the water-dispersible polymer on the ionic compound, as long as the water-soluble polymer or the water-dispersible polymer contacts the ionic compound, the polymer aqueous gel condenses or the viscosity is reduced, there is no particular limitation, for example, reaction (chemical reaction) with the ionic compound can be cited. In the case where the polymer aqueous gel is a material decomposed by enzyme treatment, a decomposing enzyme can be used, and by using culture fluid, buffer, physiological saline and water after enzyme treatment, the shape of the supporting material ink can be removed. In the case where the supporting material is a material that undergoes phase change due to temperature, it can be caused to undergo phase change by heating or cooling, and by using water or an aqueous solution after the phase change, the shape of the supporting material ink can be removed.

[0105] Examples of the ionic compound include polyvalent metal salts of calcium, zinc, magnesium, barium, strontium, copper, iron, aluminum, cobalt, etc. Among them, calcium chloride, calcium hydroxide, calcium carbonate, and calcium lactate are preferred, and calcium chloride is more preferred.

[0106] The concentration of the ionic compound in the removal solution is preferably 1 mM or more, more preferably 10 mM or more, and preferably 2 M or less, more preferably 0.2 M or less.

[0107] Examples of the degrading enzyme include cellulase, amylase, glucanase, carrageenase, alginate lyase, hyaluronidase, chitinase, and chitosanase, but are not limited thereto.

[0108] The concentration of the degrading enzyme in the removal solution is preferably 0.1% by weight to 5% by weight, more preferably 0.1% by weight to 1% by weight.

[0109] <Other Processes>

[0110] The manufacturing method of the present invention may include a step of leaving the discharged model material ink and support material ink to stand after the above-mentioned step of discharging the model material ink and the support material ink separately and before the step of removing the shaped object of the support material ink to allow the model material to fully gel.

[0111] The three-dimensional object obtained by the manufacturing method of the present invention can be made into a three-dimensional object of a complex shape, for example, made of soft materials, and can be used as an artificial organ, etc., particularly in the field of regenerative medicine. It should be noted that the shape of the three-dimensional object is not particularly limited, and is also suitable for a shape having a bridge portion and / or a hole. The size of the three-dimensional object can be set appropriately.

[0112] <<Ink set for making three-dimensional objects>>

[0113] The present invention is characterized in that it comprises: (a) a model material ink comprising a photo-crosslinkable polymer; and (b) a support material ink comprising a support material and a first crosslinking factor. The photo-crosslinkable polymer, the support material, the first crosslinking factor, and other components are as described above. Using the ink set for making a three-dimensional modeling object of the present invention, the three-dimensional modeling object of the present invention can be appropriately manufactured.

[0114] Example

[0115] The present invention will be described below with reference to Examples, but the present invention is not limited to the following Examples. Hereinafter, "parts" or "%" means "parts by weight" or "% by weight" respectively, unless otherwise specified.

[0116] Manufacturing Example 1 (Preparation of Model Material Ink 1)

[0117] 10 g of sodium hyaluronate (manufactured by Fujimedica Co., Ltd.) was dissolved in 1 L of 0.1 M 2-Morpholinoethanesulfonic acid monohydrate (MES) buffer (pH 5.8). A solution prepared by dissolving 0.56 g of tyramine hydrochloride, 1.43 g of water-soluble carbodiimide (WSCD·HCl) and 0.43 g of N-hydroxysuccinimide (NHS) in 10 mL of purified water was further added, and the mixture was stirred at room temperature for 22 hours. The obtained reaction mixture was filtered by ultrafiltration and freeze-dried in a vacuum to prepare HYA-Ph (modification rate of phenolic hydroxyl group: 2.9 mol%, Mw: 300,000).

[0118] 20 mg of the prepared HYA-Ph was weighed and dissolved in 2.0 mL of phosphate buffered saline (PBS). 3.0 mg of tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate (molecular weight 640.53 (anhydrous), 748.62 (hexahydrate)) was weighed and added to the HYA-Ph solution to prepare Ru 2+ Model material ink 1 with a concentration of 2.0 mmol / L and a HYA-Ph concentration of 1.0 w / v%.

[0119] Manufacturing Example 2 (Preparation of Support Material Ink 1)

[0120] 4 mL of Projelly (a high viscosity type manufactured by JEX INC.) was dispensed, and 9.524 mg of sodium persulfate (SPS, MW 238.10) was added to prepare support material ink 1 containing 10 mM of SPS.

[0121] Manufacturing Example 3 (Preparation of Model Material Ink 2)

[0122] 20 mg of HYA-Ph prepared in Preparation Example 1 was weighed and dissolved in 2.0 mL of phosphate buffered saline (PBS). 3.0 mg of tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate (molecular weight 640.53 (anhydrous), 748.62 (hexahydrate)) and 4.8 mg of sodium persulfate (SPS, MW 238.10) were weighed and added to the HYA-Ph solution to prepare Ru 2+ Model material ink 2 with a concentration of 2.0 mmol / L, an SPS concentration of 10.0 mmol / L, and a HYA-Ph concentration of 1.0 w / v%.

[0123] Manufacturing Example 4 (Preparation of Model Material Ink 3)

[0124] A solution in which gelatin (Sigma) was dispersed at 10 (w / v)% in phosphate buffered saline was heated to 50°C to dissolve the gelatin, and then methacrylic anhydride was added in an amount of 60% of the gelatin mass, and stirred for 1 hour. Then, a dialysis membrane (molecular weight cutoff 10,000-20,000) was placed and dialyzed with purified water at 40°C for 3 days. After the dialysis was completed, gelatin methacrylate was obtained by freeze vacuum drying.

[0125] 100 mg of gelatin methacrylate was weighed, and 5 mg of fluorescent particles (fluorescent powder, model: MB-8502, manufactured by Matsuno Industries, Ltd.) and 2.0 mL of phosphate buffered saline (PBS) were added and dissolved to prepare model material ink 3 having a gelatin methacrylate concentration of 5 w / v%.

[0126] Manufacturing Example 5 (Preparation of Support Material Ink 2)

[0127] 4 mL of Projelly (high viscosity type, manufactured by JEX INC.) was dispensed, and 40 mg of LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) was added to prepare support material ink 2 containing 1 w / v% of LAP.

[0128] Manufacturing Example 6 (Preparation of Support Material Ink 3)

[0129] In Production Example 5, a supporting material ink 3 not containing LAP was prepared in the same manner as in Production Example 5, except that LAP was not added.

[0130] Manufacturing Example 7 (Preparation of Model Material Ink 4)

[0131] 100 mg of gelatin methacrylate was weighed, 5 mg of fluorescent particles (fluorescent powder, model: MB-8502, manufactured by Matsuno Industries Co., Ltd.) and 2.0 mL of phosphate buffered saline (PBS) were added for dissolution, and LAP was added at 1 w / v% to prepare ink 4 for model material with a gelatin methacrylate concentration of 5 w / v%.

[0132] Manufacturing Example 8 (Preparation of Model Material Ink 5)

[0133] A solution of modified polyvinyl alcohol (AF-17 manufactured by JAPAN VAM & POVAL CO., LTD.) dissolved at 3.3 (w / v)% in 0.1 M 2-morpholinoethanesulfonic acid monohydrate (2-Morpholinoethanesulfolic acid monohydrate, MES) buffer (pH 6.0) was heated at 120°C for 15 minutes. After cooling to room temperature, tyramine hydrochloride, water-soluble carbodiimide (WSCD·HCl) and N-hydroxysuccinimide (NHS) were added in such a manner that they became 3.3, 3.3 and 1.0 (w / v)% respectively, and then stirred at 40°C for 20 hours. The obtained reaction solution was added to ethanol to precipitate it, and the precipitate was washed with 90% ethanol aqueous solution and ethanol, and dried under reduced pressure to prepare PVA-Ph (modification rate of phenolic hydroxyl group: 2.4×10 -4 Model material ink 5 was prepared in the same manner as in Production Example 1 so that the concentration of the prepared PVA-Ph was 5.0 w / v% (g / 100 mL).

[0134] Manufacturing Example 9 (Preparation of Model Material Ink 6)

[0135] 10 g of gelatin (manufactured by JELLICE Co., Ltd.) was dissolved in 500 mL of 0.05 M 2-morpholinoethanesulfonic acid monohydrate (2-Morpholinoethanesulfolic acid monohydrate, MES) buffer (pH 6.0). A solution prepared by dissolving 1.84 g of tyramine hydrochloride, 1.85 g of water-soluble carbodiimide (WSCD·HCl) and 0.57 g of N-hydroxysuccinimide (NHS) in 5 mL of purified water was further added, and the mixture was stirred at room temperature for 20 hours. The obtained reaction mixture was filtered by ultrafiltration and freeze-dried in a vacuum to prepare Gela-Ph (modification rate of phenolic hydroxyl group: 2.7×10 -4Model material ink 6 was prepared in the same manner as in Production Example 1 so that the concentration of the prepared Gela-Ph was 4.0 w / v% (g / 100 mL).

[0136] Manufacturing Example 10 (Preparation of Model Material Ink 7)

[0137] Dissolve 10 g of sodium alginate (manufactured by Maikon no Kohara Corporation) in 600 mL of 0.05 M 2-Morpholinoethanesulfonic acid monohydrate (MES) buffer (pH 6.0). Further add a solution prepared by dissolving 0.57 g of tyramine hydrochloride, 2.90 g of water-soluble carbodiimide (WSCD·HCl) and 0.87 g of N-hydroxysuccinimide (NHS) in 10 mL of pure water, and stir at room temperature for 19 hours. Filter the obtained reaction mixture by ultrafiltration and freeze-dry in a vacuum to prepare Alg-Ph (modification rate of phenolic hydroxyl group: 3.1 mol%). Prepare ink 7 for model material in the same manner as in Manufacturing Example 1, in such a manner that the prepared Alg-Ph has a concentration of 2.0 w / v% (g / 100 mL).

[0138] Example 1

[0139] Using a 3D printer (product name: BIO X, manufactured by Cellink), the model material ink 1 prepared in Manufacturing Example 1 and the support material ink 1 prepared in Manufacturing Example 2 were discharged onto a substrate while being exposed to form layers, and this operation was repeated to stack the layers, thereby producing a hexagonal tube with a thickness of 1 mm, a height of 5 mm, and a side length of 6 mm as a 3D object. The wavelength of the exposure light was 450 nm, and the light intensity was about 60,000 lux.

[0140] The obtained structure was immersed in a calcium chloride solution (concentration: 100 mM) to remove the structure of the support material ink.

[0141] Comparative Example 1

[0142] A three-dimensional object was produced in the same manner as in Example 1 except that the model material ink 2 produced in Production Example 3 was used and the support material ink was not used.

[0143] Figure 5A photograph of the produced three-dimensional object is shown in FIG. Even at a low concentration of 1 w / v% that is not suitable for three-dimensional objects, a three-dimensional object faithful to the original data can be produced as shown in Example 1 by using a support material ink containing a cross-linking factor. On the other hand, when a model material ink containing the first cross-linking factor is used and no support material is used, as shown in Comparative Example 1, the surface of the structure is uneven, the liquid cannot be well attached, and the structure cannot be obtained. The gelation time of the solution without a support material is itself quite short, and as a result, the linear structure collapses.

[0144] Example 2

[0145] Using a 3D printer (product name: BIO X, manufactured by Cellink), the model material ink 3 prepared in Manufacturing Example 4 and the support material ink 2 prepared in Manufacturing Example 5 were discharged onto a substrate while being exposed to form layers, and this operation was repeated to stack the layers, thereby producing a hexagonal tube with a thickness of 1 mm, a height of 5 mm, and a side length of 6 mm as a 3D object. The wavelength of the exposure light was 450 nm, and the light intensity was about 60,000 lux.

[0146] The obtained structure was immersed in a calcium chloride solution (concentration: 100 mM) to remove the structure of the support material ink.

[0147] Comparative Example 2

[0148] In Example 2, a three-dimensional object was produced in the same manner as in Example 2 except that the support material ink 3 containing no LAP produced in Production Example 6 was used as the support material ink.

[0149] Comparative Example 3

[0150] In Example 2, a three-dimensional object was produced in the same manner as in Example 2 except that the support material ink was not used and the model material ink 4 containing LAP produced in Production Example 7 was used.

[0151] Figure 6A photograph of the produced three-dimensional object is shown in . As in Example 2, even at a low concentration of 5 w / v% that is not suitable for three-dimensional objects, a three-dimensional object that is faithful to the original data can be produced by using a support material ink containing a cross-linking factor. On the other hand, in Comparative Example 2 in which LAP is not included in any ink, polymerization is not initiated and a three-dimensional structure cannot be obtained. In Comparative Example 3 in which LAP is included in the model material ink but no support material ink is used, the viscosity is low and the structure cannot be well stacked, and the discharged solution is entangled at the front end of the nozzle and cannot adhere to the structure. The reason is that the viscosity of the 5 w / v% gelatin methacrylate solution is low and its hydrogel is fragile, so the surface of the structure is large and it is exposed and gelled immediately after the solution is discharged. This problem cannot be solved even by reducing the amount of light.

[0152] The above results show that, when manufacturing a complex-shaped object made of a soft material (soft material), a three-dimensional object can be obtained with good molding accuracy by applying the manufacturing method of the present invention.

[0153] Example 3

[0154] A three-dimensional object was produced in the same manner as in Example 1 except that the ink 5 produced in Production Example 8 was used as the model material ink and the SPS concentration of the support material ink 1 produced in Production Example 2 was changed to 8 mM.

[0155] Example 4

[0156] A three-dimensional object was produced in the same manner as in Example 1 except that Ink 6 produced in Production Example 9 was used as the model material ink and the SPS concentration of the support material ink 1 produced in Production Example 2 was changed to 8 mM.

[0157] Example 5

[0158] A three-dimensional object was produced in the same manner as in Example 1 except that Ink 7 produced in Production Example 10 was used as the model material ink and the SPS concentration of the support material ink 1 produced in Production Example 2 was changed to 8 mM.

[0159] like Figures 7 to 9 As shown, in Example 3 using the model material ink 5 containing modified polyvinyl alcohol, Example 4 using the model material ink 6 containing gelatin, and Example 5 using the model material ink 7 containing alginate, it is possible to produce a modeled object with very good modeling accuracy in the same way as in Example 1 using the model material ink containing hyaluronic acid.

[0160] Example 6

[0161] Mouse fibroblast 10T1 / 2 cells were cultured at 1×10 5The cells / mL were dispersed in the model material ink 1 prepared in Manufacturing Example 1, and the obtained cell-containing model material ink and the support material ink prepared in Manufacturing Example 2 were used to prepare a three-dimensional shape (hexagonal cylinder with a thickness of 1 mm, a height of 1 mm, and a side length of 6 mm) in the same manner as in Example 1.

[0162] Immediately after the formation, the cell-containing formation was immersed in phosphate buffered saline (pH 7.4) containing 1 μg / mL of live cell staining reagent Calcein-AM and dead cell staining reagent PI for 10 minutes for staining. The photographs obtained by taking the results are shown in Fig.10 The cell viability was 85%, which remained high.

[0163] Description of Reference Numerals

[0164] 1, 11, 21, 31: Ink for support material

[0165] 2, 12, 22, 32: Ink for model materials

[0166] 2A, 12A, 22A, 32A: Three-dimensional objects

[0167] 2a, 12a, 22a, 32a: Bridge area

[0168] 2b, 12b, 22b, 32b: Hole

[0169] 3a, 3b, 13a, 13b, 13c, 23a, 23b, 23c, 33a, 33b, 33c: Nozzle

[0170] 4, 14, 24, 34: substrate

[0171] 5, 15, 25, 35: Remove solution

[0172] 11, 21, 31: Ink for the first supporting material

[0173] 11s, 21s, 31s: ink for the second supporting material.

Claims

1. A method for manufacturing a three-dimensional object, comprising: A step of separately discharging (a) a model material ink containing a photo-crosslinkable polymer and (b) a support material ink containing a support material and a first crosslinking factor; A step of photocuring the discharged photo-crosslinkable polymer; and The process of removing the support material ink from the molded object.

2. The method for manufacturing a three-dimensional object according to claim 1, wherein: The model material ink (a) further includes a second cross-linking factor.

3. The method for producing a three-dimensional object according to claim 1 or 2, wherein: The model material ink (a) does not substantially contain a photopolymerization initiator.

4. The method for producing a three-dimensional object according to any one of claims 1 to 3, wherein: The supporting material ink (b) does not substantially contain a photo-crosslinkable polymer or a photo-crosslinkable monomer.

5. The method for producing a three-dimensional object according to any one of claims 1 to 4, wherein: The supporting material ink (b) further includes a second cross-linking factor.

6. The method for producing a three-dimensional object according to any one of claims 1 to 5, wherein: The supporting material is a water-soluble polymer or a water-dispersible polymer.

7. The method for manufacturing a three-dimensional object according to claim 6, wherein: The water-soluble polymer or water-dispersible polymer is a water-soluble polymer or water-dispersible polymer that forms an aqueous gel that aggregates or has a reduced viscosity when reacting with an ionic compound. In the step of removing the shaped object of the support material ink, the shaped object of the support material ink (b) is removed by allowing an ionic compound to act.

8. An ink set for making a three-dimensional object, comprising: (a) a model material ink comprising a photo-crosslinkable polymer; and (b) A supporting material ink comprising a supporting material and a first cross-linking factor.

9. The ink set for producing a three-dimensional object according to claim 8, wherein: The supporting material ink (b) contains a water-soluble polymer or a water-dispersible polymer that forms an aqueous gel that is aggregated or has a reduced viscosity due to the action of an ionic compound.

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