Method for manufacturing three-dimensional-shaped article and ink set for production of three-dimensional-shaped article

Abstract

Provided are a method for manufacturing a three-dimensional-shaped article and an ink set for production of a three-dimensional-shaped article which make it possible to manufacture a three-dimensional-shaped article with good shaping precision, even when manufacturing a three-dimensional-shaped article that has a complex shape and that is made from a soft material, for example. The present invention relates to a method for manufacturing a three-dimensional-shaped article, said method comprising: a step for respectively discharging (a) a model material ink which contains an ion-crosslinkable polymer and (b) a support material ink which contains a support material and a crosslinking factor; a step for curing the discharged ion-crosslinkable polymer; and a step for removing a shaped article of the support material ink.

Description

Method for manufacturing three-dimensional object and ink set for producing three-dimensional object

[0001] The present invention relates to a method for producing a three-dimensional object and an ink set for producing a three-dimensional object, and in particular to a method for producing a three-dimensional object that is suitable for producing three-dimensional objects of complex shapes made of soft materials in fields such as regenerative medicine.

[0002] Research is being conducted into the practical application of technologies for producing three-dimensional objects using modeling devices known as three-dimensional printers in various fields. For example, in the field of regenerative medicine, there is a need to produce three-dimensional objects made of soft materials with complex shapes, including bridges and holes, for use in artificial organs. When attempting to produce such three-dimensional objects from bioink using a three-dimensional printer, the bioink often leaks (drips), causing collapse before gelling, or deformation due to gravity, so improved modeling accuracy is required.

[0003] Patent Literature 1 discloses that, with the aim of application in fields such as regenerative medicine, adding silk nanofibers to ink for 3D printing systems containing natural polymers and / or synthetic polymers reduces the viscosity when ejected from the nozzle, allowing for lower ejection pressure, while still maintaining a high viscosity on the substrate after printing, sufficiently preventing deformation of the model. However, there is a need to further expand the range of materials and develop new methods for producing three-dimensional models.

[0004] Japanese Patent Application Laid-Open No. 2020-156357

[0005] An object of the present invention is to provide a method for producing a three-dimensional object, and an ink set for producing a three-dimensional object, which can produce a three-dimensional object with good modeling accuracy, even when producing a three-dimensional object with a complex shape made of, for example, a soft material.

[0006] After extensive investigation, the inventors have found that by ejecting a modeling material ink containing an ionically cross-linkable polymer, and a supporting material ink containing a supporting material and a cross-linking factor, respectively, and then curing the ejected ionically cross-linkable polymer and removing the support material ink model to form a three-dimensional object, it is possible to produce three-dimensional objects with good modeling accuracy, even when producing three-dimensional objects with complex shapes made of soft materials, for example.

[0007] That is, the present invention (1) is a method for producing a three-dimensional object, comprising the steps of: ejecting (a) a modeling material ink containing an ionically cross-linkable polymer; and (b) a supporting material ink containing a supporting material and a cross-linking agent; curing the ejected ionically cross-linkable polymer; and removing the object modeled in the supporting material ink.

[0008] The present invention (2) is the method for producing a three-dimensionally shaped object according to the present invention (1), wherein the support material contains an enzymatically decomposable polymer.

[0009] The present invention (3) is the method for producing a three-dimensional object according to the present invention (2), in which the step of removing the object formed by the ink for supporting material (b) is carried out by the action of an enzyme.

[0010] The present invention (4) is an ink set for producing a three-dimensional object, comprising: (a) a modeling material ink containing an ionically crosslinkable polymer; and (b) a support material ink containing a support material and a crosslinking agent.

[0011] The present invention (5) is the ink set for producing a three-dimensional object according to the present invention (4), wherein the ink (b) for the support material contains an enzymatically decomposable polymer.

[0012] The present invention (6) is a method for producing a three-dimensional object, comprising the steps of: ejecting (a) a modeling material ink containing a cross-linkable polymer; and (b) a supporting material ink containing an enzymatically decomposable polymer and a cross-linking factor; cross-linking the ejected cross-linkable polymer; and removing the object modeled in the supporting material ink using an enzyme.

[0013] The present invention (7) is an ink set for producing a three-dimensional object, comprising: (a) a model material ink containing a crosslinkable polymer; and (b) a support material ink containing an enzymatically degradable polymer and a crosslinking agent.

[0014] The present invention (8) is an ink set for producing a three-dimensional object, comprising (a) a model material ink containing a crosslinkable polymer, and (b) a support material ink containing an enzymatically decomposable polymer, and the ink set is for forming a layered structure by alternately ejecting (a) the model material ink and (b) the support material ink.

[0015] According to the present invention, even when manufacturing a three-dimensional object made of a soft material and having a complex shape, the three-dimensional object can be manufactured with good modeling accuracy.

[0016] 9 is a schematic diagram illustrating a process for producing a three-dimensional object having bridge portions by the method for producing a three-dimensional object of the present invention. It is a photograph of the three-dimensional object produced in Example 1. It is a photograph of the three-dimensional object immediately after printing in Example 1, after immersion in an enzyme solution for 1 hour and then for 3 hours. It is a photograph of the three-dimensional object produced in Example 2. It is a photograph of the three-dimensional object produced in Comparative Example 1. It is a photograph of the three-dimensional object produced in Example 3. It is a photograph of the three-dimensional object produced in Examples 4 to 6. It is a photograph of the three-dimensional object produced in Examples 7 to 8 and Comparative Example 2. It is a schematic diagram illustrating a process for producing a three-dimensional object using a second support material ink in the method for producing a three-dimensional object of the present invention. It is a schematic diagram illustrating another example of the process shown in FIG. It is a schematic diagram illustrating yet another example of the process shown in FIG.

[0017] <<First Method for Producing a Three-Dimensional Object>> The first method for producing a three-dimensional object of the present invention is characterized by comprising the steps of ejecting (a) a modeling material ink containing an ionically cross-linkable polymer, and (b) a support material ink containing a support material and a cross-linking agent, respectively, curing the ejected ionically cross-linkable polymer, and removing the modeled object made of the support material ink.

[0018] The method for producing a three-dimensional object of the present invention will be briefly described below with reference to FIG. 1 . FIG. 1 is a schematic diagram illustrating the steps of producing a three-dimensional object having bridge portions by the method for producing a three-dimensional object of the present invention. FIG. 1( a) schematically illustrates the ejection of a support material ink 1 from a nozzle 3 a of a three-dimensional printer. FIG. 1( b) schematically illustrates the ejection of a model material ink 2 from a nozzle 3 b of the three-dimensional printer. Note that the nozzles 3 a and 3 b may be the same nozzle, but are preferably different. Here, the support material ink 1 is ejected, and then the model material ink 2 is ejected at a position surrounded by the support material ink 1 to form one layer, and this process is repeated to form a laminated structure.

[0019] As shown in Figures 1(a) and 1(b), the ejected supporting material ink 1 and the ejected modeling material ink 2 are in contact. For example, if the supporting material ink 1 contains a cross-linking agent along with the supporting material, the cross-linking agent is supplied from the ejected supporting material ink 1 to the ejected modeling material ink 2, cross-linking the ion-cross-linkable polymer in the ejected modeling material ink 2 and gelling the modeling material ink 2. Figure 1(c) shows a process in which, after the gelling of the modeling material ink 2 is complete, the resulting modeled object is immersed in a support material ink 1 modeling removal solution 5 to remove the modeled object made of the supporting material ink 1. Removing the modeled object made of the supporting material ink 1 also makes it possible to produce a three-dimensional modeled object 2A (modeling material ink modeled object) with a complex shape, including bridge portions 2a and holes 2b.

[0020] In the method for producing a three-dimensional object of the present invention, a three-dimensional object may be produced by ejecting a modeling material ink and a supporting material ink into a cylindrical container such as a beaker or a petri dish, a rectangular cylindrical container, or any other container of various shapes. Since the inner wall of the container serves as a support for the modeling material ink and / or the supporting material ink, a taller object can be produced. The material of the container is not particularly limited as long as it serves as a support for the modeling material ink and / or the supporting material ink, and materials such as glass and resin can be used. The container may also be produced by three-dimensional modeling.

[0021] <Step of ejecting (a) a modeling material ink containing an ionically crosslinkable polymer, and (b) a supporting material ink containing a supporting material and a crosslinking agent> In the ejecting step, the modeling material ink (a) and the supporting material ink (b) containing a supporting material and a crosslinking agent are ejected, for example, from the nozzle of a three-dimensional printer onto a target location such as a substrate. When a three-dimensional printer is used in the ink ejecting step, the three-dimensional printer is not particularly limited and may be any of an inkjet type, a laser light type, an extrusion type, etc., although an extrusion type three-dimensional printer is preferred. It is preferable that the nozzle ejecting the modeling material ink (a) is different from the nozzle ejecting the supporting material ink (b).

[0022] ((a) Modeling Material Ink Containing Ionically Crosslinkable Polymer) The modeling material ink (a) contains an ionically crosslinkable polymer, and becomes gel-like when the ionically crosslinkable polymer undergoes ion crosslinking due to a crosslinking factor contained in the support material ink. The ionically crosslinkable polymer is a polymer having functional groups such as carboxyl groups and sulfonic acid groups that can interact with divalent metal ions such as calcium, magnesium, iron (II), zinc, copper, manganese, strontium, and barium, and trivalent metal ions such as aluminum and iron (III). Such functional groups may be inherently present in the polymer or may be separately introduced into the polymer.

[0023] The ionically crosslinkable polymer is not particularly limited, and examples thereof include polysaccharides, nucleic acids, carbohydrates, proteins, polypeptides, poly(α-hydroxy acids), polylactones, polyamino acids, polyanhydrides, polyorthoesters, poly(anhydride-co-imides), polyorthocarbonates, poly(α-hydroxyalkanoates), polydioxanone, polyphosphoesters, polylactic acids, poly(L-lactide) (PLLA), poly(D,L-lactide) (PDLLA), polyglycolic acid, polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide-co-trimethylene carbonate), polyhydroxybutyrate (PHB), poly(ε-caprolactone), poly(δ-valerola), Examples of the polymer include lactone, poly(γ-butyrolactone), polycaprolactone, poly(meth)acrylic acid, polycarboxylic acid, polyallylamine hydrochloride, polydiallyldimethylammonium chloride, polyalkyleneimines such as polyethyleneimine, polypropylene fumarate, polyvinyl alcohol, polyvinylpyrrolidone, polyalkylenes such as polyethylene, polymethyl methacrylate, carbon fiber, polyalkylene glycols such as polyethylene glycol, polyalkylene oxides such as polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, poly(ethylene oxide)-co-poly(propylene oxide) block copolymers, poly(ethylene terephthalate) polyamides, and salts of these polymers. In addition, when these polymers do not have ionically crosslinkable groups, ionically crosslinkable groups can be introduced into the polymer to use it as an ionically crosslinkable polymer.

[0024] Examples of polysaccharides include cellulose, hemicellulose, dextran, hyaluronic acid, chitin, chitosan, alginic acid, polyglucuronic acid, gellan gum, xanthan gum, chondroitin sulfate, starch, pullulan, carrageenan, curdlan, fucoidan, amylose, amylopectin, pectin, and salts thereof, such as alkali metal salts, and derivatives thereof. Examples of polysaccharide derivatives include carboxymethylcellulose, methylcellulose, deacetylated chitins, and deacetylated chitosans.

[0025] Examples of proteins include simple proteins such as albumin, globulin, prolamin, glutelin, histone, protamine, fibroin, and other scleroproteins; complex proteins such as nucleoproteins, glycoproteins, chromoproteins, and phosphoproteins; and derived proteins such as gelatin, proteose, and peptone.

[0026] The salt of the ionically crosslinkable polymer is not particularly limited, and examples thereof include acid addition salts, metal salts, ammonium salts, and organic amine salts. Examples of acid addition salts include inorganic acid salts such as hydrochloride, sulfate, and phosphate; and organic acid salts such as acetate, maleate, fumarate, tartrate, and citrate. Examples of metal salts include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt, magnesium salt, aluminum salt, and zinc salt. Examples of organic amine salts include salts of morpholine, piperidine, and the like.

[0027] Among the ionically crosslinkable polymers, polysaccharides and proteins are preferred because they are easily supplied and the properties of the resulting three-dimensionally shaped object are good, with polysaccharides being more preferred. The ionically crosslinkable polymer substrate may be one of the above-mentioned types alone or two or more types may be used in combination.

[0028] The concentration of the ionically crosslinkable polymer in the modeling material ink (a) is typically 0.1 to 30% by mass, preferably 0.5 to 20% by mass, and more preferably 0.75 to 10% by mass. If the concentration of the ionically crosslinkable polymer is less than 0.1% by mass, the strength of the three-dimensional object may be insufficient. If the concentration exceeds 30% by mass, the viscosity of the modeling material ink may become too high, increasing the pressure when ejected from the nozzle and potentially affecting the properties of the modeling material ink (a). The concentration of the ionically crosslinkable polymer in the modeling material ink (a) is typically 0.1 to 30% by mass (w / v), preferably 0.5 to 20% by mass (g / 100 mL), and more preferably 0.75 to 10% by mass (g / 100 mL).

[0029] The modeling material ink (a) may contain other components in addition to the ionically crosslinkable polymer. Examples of other components include various cells, solvents, chain transfer agents, plasticizers, pH adjusters, buffers, preservatives, solvents, UV absorbers, colorants, surfactants, etc. Examples of solvents include water, phosphate-buffered saline (PBS), and mixtures of water and organic solvents. Examples of organic solvents include, but are not limited to, ethanol, glycerin, and dimethyl sulfoxide.

[0030] The modeling material ink (a) is preferably liquid at room temperature. Being liquid at room temperature allows for easy ejection using a 3D printer or the like. The viscosity of the modeling material ink (a) at 20°C is not particularly limited, but is preferably 10 mPa·s or higher, more preferably 20 mPa·s or higher, and even more preferably 50 mPa·s or higher. Furthermore, the viscosity is preferably 100,000 mPa·s or lower, more preferably 10,000 mPa·s or lower, and even more preferably 2,000 mPa·s or lower. Since the manufacturing method of the present invention can adequately prevent outflow (dripping) of the modeling material ink (a) before gelation, a low-viscosity modeling material ink (a) can be suitably used. The viscosity is measured using a cone-and-plate E-type viscometer at a rotational speed of 20 rpm.

[0031] The model material ink (a) can be produced by mixing the above-mentioned ion-crosslinkable polymer and, if necessary, other components.

[0032] ((b) Supporting material ink containing a supporting material and a cross-linking agent) The supporting material ink (b) may be one that retains its shape through cross-linking after being ejected and becomes a shaped object, but from the viewpoint of simplicity, it is preferable that the ink (b) can retain its shape by itself and become a shaped object as is. The object shaped with the supporting material ink (b) retains the shape of the modeling material ink (a) until the modeling material ink (a) has sufficiently gelled, preventing the outflow (dripping) of the modeling material ink (a) and deformation of the modeling material ink (a) due to gravity. After the modeling material ink (a) has gelled, the object shaped with the supporting material ink (b) is removed by the method described below.

[0033] The support material contained in the support material ink (b) is a polymer such as a natural polymer or a synthetic polymer. Examples of polymers include 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, methyl cellulose, hydroxyethyl cellulose, albumin, gelatin, collagen, silk fibroin, polyvinyl alcohol, and salts of these polymers. Preferred examples of the polymers include polysaccharides, nucleic acids, carbohydrates, proteins, polypeptides, polyamino acids, polylactic acid, polyethylene oxide, polyethylene imine, polyvinyl pyrrolidone, polyethylene glycol, albumin, gelatin, collagen, polyvinyl alcohol, and salts of these polymers. The salts of polysaccharides, proteins, and polymers are the same as those of the polysaccharides, proteins, and polymer-based salts described above for the polymer-based materials. The support material may also be a polymer crosslinked with a crosslinking agent.

[0034] The support material preferably contains an enzymatically degradable polymer, a water-soluble polymer, or a water-dispersible polymer. As described below, these polymers allow the shaped object to be easily removed under mild conditions using an enzyme solution, water, or an aqueous solution in the step of removing the shaped object from the support material ink (b). Here, 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.

[0035] The enzymatically degradable polymer preferably forms an aqueous polymer gel after discharge, and the formed aqueous polymer gel aggregates or reduces in viscosity upon reaction with the enzyme. Examples of such enzymatically degradable polymers include methylcellulose, carboxymethylcellulose, starch, dextran, carrageenan, chitin, chitosan, polycaprolactone, and derivatives thereof modified to facilitate gel formation. Examples of enzymes include cellulase, amylase, lipase, dextranase, carrageenase, alginate lyase, hyaluronidase, chitinase, and chitosanase, and enzymes capable of decomposing the enzymatically degradable polymer used are used.

[0036] The water-soluble or water-dispersible polymer is preferably one that forms an aqueous polymer gel after ejection, and the formed aqueous polymer gel is decomposed, aggregated, or has a reduced viscosity when exposed to chemicals. However, since the support material contains an ionic crosslinking agent such as calcium, a water-soluble or water-dispersible polymer that does not interact with ionic compounds is preferred.

[0037] From the viewpoint of further improving the pseudoplasticity of the support material ink (b), the concentration of the support material in the support material ink (b) is preferably 10% by volume or more, and more preferably 50% by volume or more. Note that when the support material ink (b) contains two or more types of support material, the above concentration refers to the total concentration of all polymers contained in the support material ink.

[0038] The support material ink (b) further contains a cross-linking agent. The cross-linking agent is a component that cross-links the ionically cross-linkable polymer in the model material ink (a). Specific examples of the cross-linking agent include ionic compounds, such as polyvalent metal salts of calcium, zinc, magnesium, barium, strontium, copper, iron, aluminum, and cobalt. Among these, calcium chloride, calcium hydroxide, calcium carbonate, and calcium lactate are preferred, with calcium chloride being more preferred.

[0039] The content of the cross-linking agent is preferably 0.1 to 50 parts by mass, and more preferably 0.5 to 30 parts by mass, per 100 parts by mass of the ionically cross-linkable polymer contained in the modeling material ink (a). The concentration of the cross-linking agent in the supporting 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, even more preferably 1 mM or more, and particularly preferably 5 mM or more.

[0040] In order to facilitate the removal of objects shaped in the support material ink, the support material ink (b) preferably does not undergo ionically crosslinking on its own, and therefore the support material ink (b) preferably does not contain substantially any ionically crosslinkable polymer or ionically crosslinkable monomer. The content of the ionically crosslinkable polymer or ionically crosslinkable monomer in the support material ink (b) is preferably 1% by mass or less, more preferably 0.1% by mass or less, and even more preferably 0% by mass.

[0041] The support material ink (b) may contain other components in addition to the polymer and cross-linking agent serving as the support material. These components include humectants such as glycerol, pH adjusters such as alkali metal hydroxides and organic amines, preservatives, colorants, solvents, plasticizers, UV absorbers, surfactants, etc. Examples of solvents include water, phosphate-buffered saline (PBS), and mixtures of water and organic solvents. Examples of organic solvents include, but are not limited to, ethanol and glycerin.

[0042] The support material ink (b) is preferably liquid or gel-like at room temperature, more preferably gel-like. Being gel-like at room temperature allows for easy modeling using a 3D printer or the like. The viscosity of the support material ink (b) at 20°C and a shear rate of 0.01 (1 / s) is preferably 10,000 mPa·s or more, more preferably 100,000 mPa·s or more, and even more preferably 500,000 mPa·s or more, from the viewpoint of being able to maintain its shape by itself. Furthermore, the upper limit of the viscosity is not particularly limited, but is usually 10,000,000 mPa·s or less.

[0043] 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 even more preferably 1000 mPa·s or more. The upper limit of the viscosity is not particularly limited, but is usually less than 10,000 mPa·s. The viscosity is a value measured using a viscosity / viscoelasticity measuring device manufactured by Thermo Fisher Scientific.

[0044] The ratio of the viscosity of the ink (b) for the support material at a shear rate of 0.01 (1 / s) to the viscosity at a shear rate of 10 (1 / s) at 20°C is preferably at least 5, more preferably at least 10, even more preferably at least 20, and particularly preferably at least 50. This provides the ink (b) with even better pseudoplasticity.

[0045] The support material ink (b) can be produced by mixing a polymer, a cross-linking agent, and, if necessary, other components. The mixing conditions are not particularly limited.

[0046] As described above, in the manufacturing method of the present invention, a three-dimensional printer is typically used to eject, for example, a modeling material ink (a) and a supporting material ink (b), respectively, to form layers, which can then be repeatedly laminated. When the ejected modeling material ink (a) and the ejected supporting material ink (b) come into contact, the ejected cross-linking agent cross-links the ionically cross-linkable polymer, thereby forming a modeled object made of the modeling material ink (a). Here, the cross-linking agent contained in the ejected supporting material ink (b) is supplied to the ejected modeling material ink (a). In the manufacturing method of the present invention, in addition to the cross-linking of the ionically cross-linkable polymer by the cross-linking agent, photocrosslinking, photocrosslinking, enzymatic cross-linking, temperature change, and the like may also contribute to the cross-linking of the cross-linkable polymer.

[0047] (Supporting Material Ink Containing Second Supporting Material) In the manufacturing method of the present invention, a second supporting material ink may be ejected together with the modeling material ink (a) and the supporting material ink (b) (hereinafter also referred to as the first supporting material ink) as a support material for the modeling material ink and the first supporting material ink. The second supporting material ink may be ejected in advance to produce a three-dimensional object (container or outer frame), or only a portion of the three-dimensional object (container or outer frame) may be produced, and the remaining portion may be produced by ejecting the modeling material ink and the first supporting material ink together. Alternatively, all of the three-dimensional object may be produced simultaneously. The three-dimensional object (container or outer frame) produced with the second supporting material ink serves as a support for the modeling material ink and the first supporting material ink, which more satisfactorily prevents the modeling material ink and the first supporting material ink from collapsing. Furthermore, a three-dimensional object with a greater height may be produced, if desired. Furthermore, such a second supporting material ink may not contain a cross-linking agent. By replacing the first supporting material ink with such a second supporting material ink and reducing the amount of the first supporting material ink ejected, the amount of cross-linking agent used in the first supporting material ink can be reduced. The second supporting material contained in the second supporting material ink is not particularly limited as long as it serves as a support for the modeling material ink and / or the supporting material ink. The supporting material used in the supporting material ink (b), glass, resin, etc., can be used. Furthermore, as described below, objects modeled with the second supporting material ink can be removed in the same way as objects modeled with the first supporting material ink by selecting an appropriate material. The modeling material ink may come into contact with an object partially or entirely composed of the second supporting material.

[0048] FIG. 9 is a schematic diagram illustrating a step of producing a three-dimensional object using a second ink for supporting material in the method for producing a three-dimensional object of the present invention. Only the differences from FIG. 1 will be described below. FIG. 9( a) schematically illustrates the ejection of the second ink for supporting material 11s from the nozzle 13a of the three-dimensional printer. FIG. 9( b) schematically illustrates the ejection of the first ink for supporting material 11 from the nozzle 13b of the three-dimensional printer. FIG. 9( c) schematically illustrates the ejection of the modeling material ink 12 from the nozzle 13c of the three-dimensional printer. Although the nozzles 13a, 13b, and 13c may be the same nozzle, it is preferable that they are different nozzles. In Figure 9, one layer is formed by ejecting second supporting material ink 11s, ejecting first supporting material ink 11 at a position surrounded by the second supporting material ink 11s, and ejecting model material ink 12 at a position surrounded by the first supporting material ink 11, and this is repeated to form a laminated structure.

[0049] 9(a) to 9(c), the ejected second supporting material ink 11s has a thin, flat wall-like shape on both the inner and outer peripheries, and contacts and supports the ejected first supporting material ink 11, and also indirectly supports the ejected modeling material ink 12. By using a second supporting material ink 11s that can form a hard object, it is possible to more effectively prevent the modeling material ink 12 and the first supporting material ink 11 from crumbling during gelation, etc. Furthermore, if desired, it is possible to produce a three-dimensional object with a greater height.

[0050] 9(d), similar to FIG. 1(c), shows a process in which, after the gelation of the modeling material ink 12 is completed, the obtained modeled object is immersed in a removal solution 15 to remove the object modeled with the first supporting material ink 11 and the object modeled with the second supporting material ink 11s. This process will be described later.

[0051] Figure 10 is the same as the schematic diagram shown in Figure 9 , except that the ejection ranges of the first supporting material ink 21 and the second supporting material ink 21s have been changed as shown in Figure 10. Below, only the differences from Figure 9 will be described. In Figure 10 , the second supporting material ink is ejected so that the inner periphery is stepped and widens downward, and compared to the case of Figure 9 , part of the first supporting material ink is replaced with the second supporting material ink. By using the second supporting material ink 21s, which is capable of forming a hard shaped object and does not contain the first cross-linking agent, it is possible to more sufficiently prevent the modeling material ink 22 and the first supporting material ink 21 from crumbling during gelation, etc., while reducing the ejection amount of the first supporting material ink 21 and saving the amount of the first cross-linking agent used.

[0052] Figure 11 is the same as the schematic diagram shown in Figure 10, except that the ejection range of the second supporting material ink 31s has been changed as shown in Figure 11. Only the differences from Figure 10 will be explained below. In Figure 11, the second supporting material ink is ejected in a stepped shape with an outer periphery that widens upward, in accordance with the shapes of the ejected modeling material ink 32 and the ejected first supporting material ink 31, and the ejection amount of the second supporting material ink can also be reduced compared to Figure 10.

[0053] <Step of curing the ejected ionically cross-linkable polymer> In the ionically curing step, the cross-linking factor that has migrated from the support material ink to the model material ink layer reacts with the ionically cross-linkable polymer in the model material ink and is cured.

[0054] <Step of Removing an Object Modeled with Supporting Material Ink> The step of removing an object modeled with the supporting material ink is not particularly limited as long as it removes an object modeled with the supporting material ink (b) and obtains an object modeled with the modeling material ink (a). For example, the step can be performed by immersing and / or washing the object modeled with the supporting material ink (b) in a modeling removal solution containing an enzyme from the supporting material ink (b). The removal step is preferably performed under mild conditions, for example, at a temperature of 10 to 40°C, in order to minimize the effect on the object modeled with the modeling material ink (a) (three-dimensional object). Furthermore, the pH of the removal solution at 20°C is preferably 2 to 10, more preferably 5 to 9, in terms of enzyme activity. The object modeled with the supporting material ink consists of the remaining components, such as supporting material molecules, after the cross-linking agent is supplied from the supporting material ink to the modeling material ink.

[0055] When the above-mentioned second supporting material ink is further used together with the supporting material ink (b), the object shaped in the supporting material ink (b) and the object shaped in the second supporting material ink may be removed using different methods, but it is preferable to remove the object shaped in the second supporting material ink along with the object shaped in the supporting material ink (b) through the above-mentioned removal step.

[0056] When the support material contains an enzymatically degradable polymer, an aqueous solution containing an enzyme capable of removing the enzymatically degradable polymer can be used as the removal solution. When the support material contains a water-soluble polymer or a water-dispersible polymer, water or an aqueous solution can be used as the removal solution. In the removal solution containing an enzyme, the concentration of the enzyme is preferably 1 to 100 mg / mL.

[0057] <Other Steps> The manufacturing method of the present invention may include, after the step of ejecting the above-mentioned modeling material ink and supporting material ink, a step of leaving the ejected modeling material ink and supporting material ink to stand in order to sufficiently gel the modeling material, before the step of removing the object shaped by the supporting material ink.

[0058] The three-dimensional object obtained by the manufacturing method of the present invention can be a three-dimensional object of a complex shape made of, for example, a soft material, and is particularly suitable for use as an artificial organ in the field of regenerative medicine. The shape of the three-dimensional object is not particularly limited, but it is also suitable for objects with bridge portions and / or holes. The dimensions of the three-dimensional object can be set as appropriate.

[0059] <<First Ink Set for Producing Three-Dimensional Objects>> The present invention is characterized by comprising (a) a modeling material ink containing an ionically cross-linkable polymer, and (b) a support material ink containing a support material and a cross-linking agent. The ionically cross-linkable polymer, support material, cross-linking agent, and other components are as described above. The three-dimensional object of the present invention can be suitably produced using the ink set for producing three-dimensional objects of the present invention.

[0060] <<Second Method for Producing a Three-Dimensional Object>> The second method for producing a three-dimensional object of the present invention is characterized by comprising the steps of ejecting (a) a model material ink containing a crosslinkable polymer and (b) a support material ink containing an enzymatically decomposable polymer and a crosslinking agent, respectively, curing the ejected crosslinkable polymer, and removing the model of the support material ink using an enzyme.

[0061] The crosslinkable polymer contained in the modeling material ink (a) containing a crosslinkable polymer is not particularly limited, and examples thereof include enzymatically crosslinkable polymers, photocrosslinkable polymers, and ionically crosslinkable polymers. Enzymatically crosslinkable polymers include, but are not limited to, polymers obtained by bonding a polymer with a compound having a phenolic hydroxyl group, amino-group-containing polysaccharides, polyphenols, etc. Photocrosslinkable polymers include, but are not limited to, polymers obtained by bonding a polymer with a compound having a phenolic hydroxyl group, polymers having (meth)acrylate groups such as gelatin methacrylate, amino-group-containing polysaccharides, polyphenols, etc. When a polymer has photocrosslinkable functional groups, it may be used as a photocrosslinkable polymer as is, or it may be further bonded to a compound having a phenolic hydroxyl group to introduce photocrosslinkable functional groups. Ionically crosslinkable polymers are as described above. The polymers used in enzymatically crosslinkable polymers and photocrosslinkable polymers can be the same as those described as ionically crosslinkable polymers.

[0062] The cross-linking agent contained in the support material ink (b), which contains an enzymatically degradable polymer and a cross-linking agent, is a component that cross-links the cross-linkable polymer contained in the model material ink (a), which contains a cross-linkable polymer. Furthermore, when the cross-linkable polymer is an enzymatically cross-linkable polymer, examples of the cross-linking agent include hydrogen peroxide, a hydrogen peroxide donor, or a hydrogen peroxide decomposer. When the cross-linkable polymer is a photocross-linkable polymer, examples of the cross-linking agent include polymerization initiators such as sodium peroxodisulfate (SPS), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), diphenyl-2,4,6-trimethylbenzoylphosphine oxide, and 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone.

[0063] The enzymatically degradable polymer contained in the support material ink (b) containing an enzymatically degradable polymer and a crosslinking agent is as described above. Note that when the crosslinkable polymer contained in the model material ink (a) is an enzymatically crosslinkable polymer, it is preferable that the enzymatically degradable polymer is a polymer that is not decomposed by the enzyme.

[0064] <<Second Ink Set for Producing Three-Dimensional Objects>> The second ink set for producing three-dimensional objects of the present invention is characterized by comprising (a) a model material ink containing a crosslinkable polymer, and (b) a support material ink containing an enzymatically degradable polymer and a crosslinking agent. The crosslinkable polymer, enzymatically degradable polymer, crosslinking agent, and other components are as described above. The three-dimensional object of the present invention can be suitably produced using the second ink set for producing three-dimensional objects of the present invention.

[0065] <<Third Ink Set for Producing Three-Dimensional Objects>> The third ink set for producing three-dimensional objects of the present invention comprises (a) a model material ink containing a crosslinkable polymer, and (b) a support material ink containing an enzymatically degradable polymer, and is used to form a layered structure by alternately ejecting (a) the model material ink and (b) the support material ink. The crosslinkable polymer, the enzymatically degradable polymer, and other components are as described above. The three-dimensional object of the present invention can be suitably produced using the third ink set for producing three-dimensional objects of the present invention. The third ink set for producing three-dimensional objects of the present invention is an ink set that is optimal for a method of alternately ejecting (a) the model material ink and (b) the support material ink to form a layered structure.

[0066] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples. Hereinafter, "parts" and "%" mean "parts by mass" and "% by mass", respectively, unless otherwise specified.

[0067] Production Example 1 (Model Material Ink 1) Sodium alginate (Kimica Algin I-3, manufactured by Kimica Co., Ltd., 300-400 mPa·s) was weighed out, and Ca ２＋A 1.0 w / v% solution was prepared by adding CF-KRH-free Krebs Ringer Hepes buffer solution to the solution, and then fluorescent particles (fluorescent powder, manufactured by Matsuno Kogyo Co., Ltd.) were dispersed therein to prepare model material ink 1.

[0068] Production Example 2 (Model Material Ink 2) Sodium alginate (Kimica Algin I-3, manufactured by Kimica Co., Ltd., 300-400 mPa s) was weighed out and ultrapure water was added to prepare a 2.0 w / v % solution. Fluorescent particles (fluorescent powder, manufactured by Matsuno Kogyo Co., Ltd.) were then dispersed in the solution to prepare Model Material Ink 2.

[0069] Production Example 3 (Model Material Ink 3) Polyglucuronic acid was weighed, and Ca ２＋ A 2.0 w / v % solution was prepared by adding CF-KRH-free Krebs Ringer Hepes buffer solution to the mixture. Fluorescent particles (fluorescent powder, manufactured by Matsuno Kogyo Co., Ltd.) were then dispersed in the solution to prepare model material ink 3.

[0070] Production Examples 4 to 9 (Support Material Inks 1 to 6) Starch glue (Fuekinori Kogyo Co., Ltd., Animal Glue, FD6) with 10M CaCl ２ The solution was added, and the starch paste concentration and Ca ２＋ Support material inks 1 to 6 having different densities were prepared.

[0071] Production Examples 10 to 12 (Enzyme Solutions 1 to 3) α-Amylase (Kishida Chemical Co., Ltd., 260-04412) was weighed, and the solvents shown in Table 1 were added to prepare 1 mg / mL enzyme solutions 1 to 3. In Table 1, CF-KRH represents Ca ２＋ -free Krebs Ringer Hepes buffer, and the pH of the simulated body fluid is 7.4.

[0072] Details of the inks prepared in each production example are shown below.

[0073] Examples 1 to 8 and Comparative Examples 1 to 2 Using a three-dimensional printer (product name: BIO X, manufactured by Celllink), the model material ink and support material ink prepared in the production examples shown in Table 2 were each ejected onto a substrate to form layers, which were then repeatedly stacked to produce three-dimensional objects (hexagonal tubes with a thickness of 1 mm, height of 5 mm, and side length of 6 mm). After leaving the structure for 5 minutes, the support material was still attached and immersed in 15 mL of the enzyme solution prepared in the production examples shown in Table 2 at 37°C for 3 hours to remove the support material, and the three-dimensional objects of each example were produced.

[0074]

[0075] Figure 2 shows a design drawing of the three-dimensional structure produced in Example 1, and photographs of the three-dimensional structure before and after removal of the support material. A three-dimensional structure could be produced by ionic crosslinking, and the support material could be removed by the enzyme.

[0076] 3 shows photographs of the three-dimensional structure produced in Example 1 immediately after printing, after immersion in the enzyme solution for one hour, and after immersion for three hours. Under the conditions of Example 1, the support material could be completely removed by immersion in the enzyme solution for three hours.

[0077] FIG. 4 shows a design drawing of the three-dimensional object fabricated in Example 2 and photographs of the three-dimensional object before and after removal of the support material. ２＋ Even when the concentration of Ca was 10 mM, a three-dimensional structure could be produced by ionic crosslinking in the same manner as in Example 1, and the support material could be removed by the enzyme. ２＋ The decrease in concentration resulted in insufficient gelation and reduced molding accuracy.

[0078] 5 shows a design drawing of the 3D object produced in Comparative Example 1, and photographs of the 3D object before and after removal of the support material. Because the ionically cross-linkable polymer did not gel, the alginic acid solution also flowed out when the support material was removed, making it impossible to produce a 3D object.

[0079] 6 shows a design drawing of the three-dimensional object fabricated in Example 3 and photographs of the three-dimensional object before and after removal of the support material. ２＋ Even when the concentration of the support material was 10 mM, a three-dimensional structure could be produced by ionic crosslinking, and the support material could be removed by the enzyme.

[0080] 7 shows photographs of the three-dimensional objects produced in Examples 4 to 6, as well as the three-dimensional objects before and after removal of the support material. When the starch concentration in the support material ink decreased, the viscosity decreased, and the modeling accuracy also decreased.

[0081] FIG. 8 shows photographs of the three-dimensional structures produced in Examples 7 and 8 and Comparative Example 2, as well as photographs of the three-dimensional structures before and after removal of the support material. ２＋ At concentrations of 50 mM and 100 mM, a three-dimensional structure could be produced by ionic crosslinking, as in Example 1, and the support material could also be removed by the enzyme.

[0082] From the above results, it was found that when manufacturing objects with complex shapes made of soft materials, by applying the manufacturing method of the present invention using ionically cross-linkable polymers, it is possible to obtain three-dimensional objects with good modeling accuracy.

[0083] 1, 11, 21, 31: Ink for supporting material 2, 12, 22, 32: Ink for modeling material 2A, 12A, 22A, 32A: Three-dimensional object 2a, 12a, 22a, 32a: Bridge portion 2b, 12b, 22b, 32b: Hole 3a, 3b, 13a, 13b, 13c, 23a, 23b, 23c, 33a, 33b, 33c: Nozzle 4, 14, 24, 34: Substrate 5, 15, 25, 35: Removal solution 11, 21, 31: Ink for first supporting material 11s, 21s, 31s: Ink for second supporting material

Claims

1. A method for manufacturing a three-dimensional object, comprising the steps of: ejecting (a) a modeling material ink containing an ionically cross-linkable polymer; and (b) a supporting material ink containing a supporting material and a cross-linking agent; curing the ejected ionically cross-linkable polymer; and removing the object modeled in the supporting material ink.

2. The method for producing a three-dimensional object according to claim 1, wherein the support material contains an enzymatically decomposable polymer.

3. The method for producing a three-dimensional object according to claim 2, wherein in the step of removing the object formed by the ink for supporting material, an enzyme is allowed to act on the object formed by the ink for supporting material (b).

4. An ink set for producing three-dimensional objects, comprising: (a) a modeling material ink containing an ionically cross-linkable polymer; and (b) a support material ink containing a support material and a cross-linking agent.

5. The ink set for producing a three-dimensional object according to claim 4, wherein the ink (b) for the support material contains an enzymatically decomposable polymer.

6. A method for manufacturing a three-dimensional object, comprising the steps of: ejecting (a) a modeling material ink containing a cross-linkable polymer; and (b) a supporting material ink containing an enzymatically decomposable polymer and a cross-linking factor; cross-linking the ejected cross-linkable polymer; and removing the object formed in the supporting material ink using an enzyme.

7. An ink set for producing three-dimensional objects, comprising: (a) an ink for a model material containing a cross-linkable polymer; and (b) an ink for a support material containing an enzymatically degradable polymer and a cross-linking factor.

8. An ink set for producing three-dimensional objects, comprising: (a) an ink for a model material containing a cross-linkable polymer; and (b) an ink for a support material containing an enzymatically decomposable polymer, the ink set being for forming a layered structure by alternately ejecting (a) the ink for the model material and (b) the ink for the support material.

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