3D printing support material and method for manufacturing same

Abstract

Provided is a 3D printing support material containing gel particles that have a small particle diameter and narrow particle size distribution. This 3D printing support material contains gel particles and a gel particle stabilizer. The number-average diameter D50 of the gel particles, which is the particle diameter corresponding to a number accumulation of 50% in a number-based particle size distribution, is 1 μm to 500 μm, and, in the particle size distribution, the ratio (D90 / D10) of D90, which is the particle diameter corresponding to a number accumulation of 90%, relative to D10, which is the particle diameter corresponding to a number accumulation of 10%, is 7 or lower.

Description

3D printing support material and method for manufacturing the same

[0001] The present invention relates to a support material for 3D printing and a method for producing the same.

[0002] Three-dimensional (3D) printing is an innovative technology that has emerged as a powerful platform for constructing complex structures and is applicable to a wide variety of applications. Traditional 3D printing typically builds 3D structures on a substrate by adding material layer by layer. However, it is difficult to directly apply this method to print soft, hydrous biomaterials. This is because gravity can cause the printed structure to collapse during the printing process. To overcome this drawback, bath-supported 3D printing, which is composed of a support medium, has been developed. Among various bath systems, gel particle baths are one of the frequently used support materials in bioprinting due to their high water content and smooth transition between the fluid and solid states.

[0003] In relation to the above, for example, JP-A No. 2021-512742 and Science, 365, 482-487 (2019) describe a hydrogel containing a gelatin microparticle slurry as a support material.

[0004] The resolution of 3D printing using a gel particle bath as a support material depends on the particle size and size distribution of the gel particles. Conventional techniques have made it difficult to easily and mass-produce gel particles with small particle sizes and narrow particle size distributions.

[0005] One aspect of the present invention aims to provide a support material for 3D printing containing gel particles with a small particle size and a narrow particle size distribution, and a method for producing the same.

[0006] Specific means for solving the above problems are as follows, and the present invention encompasses the following aspects: A first aspect is a support material for 3D printing comprising gel particles and a gel particle stabilizer, wherein the gel particles have a number average diameter D50 of 1 μm or more and 500 μm or less, which is a particle diameter corresponding to 50% of the number of cumulative particles in a number-based particle size distribution, and the ratio (D90 / D10) of D90, which is a particle diameter corresponding to 90% of the number of cumulative particles, to D10, which is a particle diameter corresponding to 10% of the number of cumulative particles in the particle size distribution, is 7 or less.

[0007] The gel particles may contain at least one selected from the group consisting of gellan gum, alginic acid, gelatin, collagen, gum arabic, gintan gum, cellulose, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol gel, starch, and fibrin. The gel particle stabilizer may contain at least one selected from the group consisting of a carboxylic acid compound, a water-soluble organic solvent, and a salt.

[0008] A second aspect is a method for producing a support material for 3D printing, comprising providing a mixture comprising a gel and a gel particle stabilizer solution, and applying shear force to the mixture to obtain a gel particle dispersion.

[0009] The gel may contain at least one selected from the group consisting of gellan gum, alginic acid, gelatin, collagen, gum arabic, gintan gum, cellulose, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol, starch, and fibrin. The gel particle stabilizer may contain at least one selected from the group consisting of a carboxylic acid compound, a water-soluble organic solvent, and a salt. The gel particles may have a number-average diameter D50, which is the particle size corresponding to 50% of the cumulative number in a number-based particle size distribution, of 1 μm or more and 500 μm or less, and a ratio (D90 / D10) of D90, which is the particle size corresponding to 90% of the cumulative number in the particle size distribution, to D10, which is the particle size corresponding to 10% of the cumulative number in the particle size distribution, of 7 or less.

[0010] According to the present invention, it is possible to provide a 3D printing support material containing gel particles having a small particle size and a narrow particle size distribution, and a method for producing the same.

[0011] 8 is an example of a microscope image of a 3D printing support material according to Comparative Example 1. FIG. 9 is an example of a microscope image of a 3D printing support material according to Example 3. FIG. 10 is an example of a particle size distribution of gel particles in a 3D printing support material according to Comparative Example 1. FIG. 11 is an example of a particle size distribution of gel particles in a 3D printing support material according to Example 3. FIG. 12 is an example of a particle size distribution of gel particles in a 3D printing support material according to Example 5. FIG. 13 is an example of a particle size distribution of gel particles in a 3D printing support material according to Example 6. FIG. 14 is an example of a three-dimensional structure formed in a 3D printing support material, which is a graph showing the change in width in the length direction of the collagen fiber of FIG. 7, which is an example of a microscope image of a collagen fiber formed in the 3D printing support material. FIG. 15 is another example of a three-dimensional structure formed in a 3D printing support material.

[0012] As used herein, the term "process" refers not only to an independent process, but also to processes that cannot be clearly distinguished from other processes, as long as the intended purpose of the process is achieved. Furthermore, the content of each component in a composition refers to the total amount of the multiple substances present in the composition, unless otherwise specified, when multiple substances corresponding to each component are present in the composition. Furthermore, the upper and lower limits of the numerical ranges described herein can be arbitrarily selected and combined from the numerical values ​​exemplified as numerical ranges. Hereinafter, embodiments of the present invention will be described in detail. However, the embodiments described below are intended to exemplify 3D printing support materials and methods for producing the same in order to embody the technical concept of the present invention, and the present invention is not limited to the 3D printing support materials and methods for producing the same shown below.

[0013] 3D Printing Support Material The 3D printing support material includes gel particles and a gel particle stabilizer. The number-average diameter D50, which is the particle size corresponding to 50% of the cumulative number in the number-based particle size distribution of the gel particles constituting the 3D printing support material, may be, for example, 1 μm or more and 500 μm or less. Furthermore, the ratio (D90 / D10) of D10, which is the particle size corresponding to 10% of the cumulative number in the particle size distribution, to D90, which is the particle size corresponding to 90% of the cumulative number, may be, for example, 7 or less.

[0014] The 3D printing support material contains gel particles and a gel particle stabilizer, which allows it to achieve a predetermined number-average diameter D50 and a predetermined D90 / D10 ratio. This allows for the production of desired structures with excellent resolution in 3D printing. Furthermore, the 3D printing support material can be efficiently produced using the production method described below.

[0015] The number-average diameter D50 of the gel particles may preferably be 0.1 μm or more, 10 μm or more, 15 μm or more, or 20 μm or more. The number-average diameter D50 of the gel particles may preferably be 200 μm or less, 50 μm or less, 40 μm or less, or 30 μm or less. The D90 / D10 of the gel particles may be, for example, 10 or less, 7 or less, 6 or less, 5 or less, 4 or less, or 3 or less. The lower limit of D90 / D10 of the gel particles may be, for example, 1 or more, or 2 or more.

[0016] D10, which is the particle size corresponding to 10% cumulative number in the particle size distribution of gel particles, may be, for example, 5 μm or more and 50 μm or less. D10 may preferably be 8 μm or more, 10 μm or more, or 12 μm or more, and may preferably be 40 μm or less, 30 μm or less, 20 μm or less, or 16 μm or less. D90, which is the particle size corresponding to 90% cumulative number in the particle size distribution of gel particles, may be, for example, 20 μm or more and 100 μm or less. D90 may preferably be 25 μm or more, 30 μm or more, or 35 μm or more, and may preferably be 80 μm or less, 60 μm or less, 40 μm or less, or 38 μm or less.

[0017] The number-based particle size distribution of gel particles can be obtained, for example, by measuring the particle size of individual gel particles using image analysis software in a microscopic image obtained by observing the 3D printing support material with a confocal laser scanning microscope.

[0018] The gel material constituting the gel particles contained in the 3D printing support material can be any substance that can be gelled by the addition of ions, temperature change, etc., as long as it does not adversely affect the formation of a structure formed by 3D printing. Examples of such gel materials include gums such as gellan gum (GG), alginic acid, polyacrylic acid, polyglutamic acid, polyaspartic acid, gelatin, collagen, gum arabic, gintan gum, cellulose, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol, starch, and fibrin. The gel material may preferably contain at least one selected from the group consisting of gellan gum, alginic acid, gelatin, collagen, gum arabic, gintan gum, cellulose, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol, starch, and fibrin.

[0019] More preferably, the gel material may include at least one selected from the group consisting of gellan gum, collagen, gintan gum, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol, starch, and fibrin.

[0020] The gel material constituting the gel particles may be a hydrogel. The gel material constituting the gel particles may be one type alone or a combination of two or more types. Matrigel is a trade name for an extracellular matrix sold by BD Biosciences, and is a mixture of laminin, nidogen, collagen, heparan sulfate proteoglycan, etc.

[0021] The gel material constituting the gel particles may preferably be a gum. Gums include plant-derived gums, bacterial-derived gums, and algae-derived gums. Specific examples of plant-derived gums include guar gum, locust bean gum, cassia gum, tragacanth gum, tara gum, karaya gum, acacia gum, ghatti gum, cherry gum, cashew gum, apricot gum, tamarind gum, mesquite gum, larch gum, plantain, and fenugreek gum. Gums derived from bacteria and algae include xanthan gum, seaweed gum, gellan gum, agar gum, carrageenan, and curdlan.

[0022] Among gums, gellan gum (GG) is a linear, natural polymeric polysaccharide produced extracellularly by Pseudomonas elodea using glucose or other carbon sources. GG forms a transparent, heat-resistant, and acid-resistant gel in the presence of monovalent or divalent metal salts. GG includes HA gellan gum, which contains a high amount of acyl groups, and LA gellan gum, which has acyl groups removed. Either type may be used in the present invention. Alternatively, both types of GG may be used in combination. GG is commercially available, for example, as Nanogel (registered trademark)-TC, Grovgel, AppliedGel, Phytagel (trademark), or Gelrite.

[0023] The gel particles may contain a liquid carried by the gel material in addition to the gel material. The liquid carried by the gel material can be appropriately selected depending on the type of gel material, etc. Specific examples of the liquid carried by the gel material include water and phosphate buffered saline.

[0024] The content of the gel material in the gel particles can be appropriately selected depending on the type of gel material, the type of liquid held by the gel material, etc. The content of the gel material in the gel particles may be, for example, 0.01% by mass or more and 30% by mass or less. The content of the gel material in the gel particles may be preferably 0.1% by mass or more, or 0.3% by mass or more, and may be preferably 10% by mass or less, 5% by mass or less, 2% by mass or less, 1% by mass or less, or 0.8% by mass or less.

[0025] The gel particle stabilizer contained in the 3D printing support material is not particularly limited as long as it exhibits the property of removing at least a portion of the solvent that constitutes the gel from the gel. Furthermore, the gel particle stabilizer may be selected appropriately depending on the gel material that constitutes the gel particles. The gel particle stabilizer is preferably water-soluble. Here, water-soluble means that the solubility in 100 g of pure water at 25°C is 1 g or more.

[0026] Specific examples of gel particle stabilizers include carboxylic acid compounds, water-soluble organic solvents, salts, etc. Specific examples of carboxylic acid compounds include monocarboxylic acids such as lactic acid and glycolic acid, dicarboxylic acids such as malic acid, and tricarboxylic acids such as citric acid. The carboxylic acid compounds may be used as salts with alkali metals, alkaline earth metals, etc. Examples of water-soluble organic solvents that can be used as gel particle stabilizers include alcohols such as ethanol, propanol, and isopropanol, and nitriles such as acetonitrile. Examples of salts include alkali metal salts and alkaline earth metal salts such as calcium chloride, sodium chloride, potassium chloride, magnesium chloride, aluminum chloride, sodium sulfate, calcium sulfate, magnesium sulfate, potassium sulfate, sodium nitrate, potassium nitrate, calcium nitrate, sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate.

[0027] From the viewpoint of dispersion stability of the gel particles, the gel particle stabilizer is preferably a carboxylic acid compound, more preferably a polycarboxylic acid compound such as a dicarboxylic acid or tricarboxylic acid.

[0028] The 3D printing support material may further contain a liquid medium in addition to the gel particles and gel particle stabilizer. The liquid medium may be any liquid medium capable of dissolving the gel particle stabilizer, and may include, for example, water. The concentration of the gel particle stabilizer in the liquid medium may be appropriately selected depending on the type of gel particle stabilizer. For example, when the gel stabilizer is a carboxylic acid compound, the concentration of the gel particle stabilizer in the liquid medium may be 0.1 mM or more and 1 M or less. When the gel stabilizer is a carboxylic acid compound, the concentration of the gel particle stabilizer in the liquid medium may be preferably 10 mM or more, 100 mM or more, 200 mM or more, 300 mM or more, or 400 mM or more, and may be preferably 0.7 M or less, 0.6 M or less, or 0.5 M or less. For example, when the gel stabilizer is a water-soluble organic solvent, the concentration of the gel particle stabilizer in the liquid medium may be 1 vol% or more and 99 vol% or less. When the gel stabilizer is a water-soluble organic solvent, the concentration of the gel particle stabilizer in the liquid medium may preferably be 5% by volume or more, 10% by volume or more, 20% by volume or more, 25% by volume or more, or 30% by volume or more, and may preferably be 60% by volume or less, 50% by volume or less, 40% by volume or less, or 35% by volume or less.

[0029] When the 3D printing support material includes a liquid medium, the concentration of gel particles in the 3D printing support material may be, for example, 1% by volume or more and 99% by volume or less. The concentration of gel particles in the 3D printing support material including a liquid medium may be preferably 10% by volume or more, or 30% by volume or more, and may be preferably 80% by volume or less, or 70% by volume or less.

[0030] The 3D printing support material may contain a surfactant if necessary. The surfactant may be nonionic, cationic, anionic, amphoteric, or the like, and is preferably nonionic. Examples of nonionic surfactants include polyoxyalkylene alkyl ethers, polyoxyethylene polyoxypropylene alkyl ethers (the addition form of ethylene oxide and propylene oxide may be either random or block), polyethylene glycol propylene oxide adducts, polypropylene glycol ethylene oxide adducts, and glycerin fatty acid esters or ethylene oxide adducts thereof. The surfactant content in the 3D printing support material may be, for example, greater than 0% by mass and 5% by mass or less. The surfactant content may preferably be 0.01% by mass or more, or 0.1% by mass or more. The surfactant content may also preferably be 2% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, or 0.01% by mass or less.

[0031] The 3D printing support material can be used for 3D printing. For example, 3D printing can be performed by ejecting 3D printing ink into the 3D printing support material in a desired shape. The 3D printing ink may contain, for example, organic substances such as collagen, fibrinogen, gelatin, and alginic acid, or inorganic substances such as silica and nanoclay.

[0032] A method for manufacturing a support material for 3D printing may include a preparation step of preparing a mixture containing a gel and a gel particle stabilizer, and a dispersion step of applying shear force to the prepared mixture to obtain gel particles. The dispersion of gel particles obtained in the dispersion step may constitute the support material for 3D printing.

[0033] By applying shear force to a gel in the presence of a gel particle stabilizer, a 3D printing support material containing gel particles with a small particle size and a narrow particle size distribution can be efficiently produced with excellent productivity. Note that when gel particles are prepared by applying shear force to a gel in the absence of a gel particle stabilizer, the resulting gel particles will have a broad particle size distribution with a ratio (D90 / D10) of more than 7.

[0034] The gel contained in the mixture may be formed by supporting the aforementioned liquid on the aforementioned gel material, and the gel material and liquid constituting the gel may be appropriately selected depending on the purpose, etc. For example, the gel can be prepared by mixing the gel material with the liquid, heating to dissolve the gel material in the liquid, and then lowering the temperature to gel. The gel may also be prepared by a chemical reaction.

[0035] The gel constituting the mixture may be particulate. Particulate gels can be prepared, for example, by applying an appropriate shear force to the prepared gel. Examples of methods for applying shear force include a method using a homogenizer, ultrasonic treatment, and a method using a filter mesh.

[0036] Details of the gel particle stabilizer contained in the mixture are as described above. The mixture may further contain a liquid medium in addition to the gel particles and the gel particle stabilizer. The liquid medium may be any medium capable of dissolving the gel particle stabilizer, and may contain, for example, water. The concentration of the gel particle stabilizer in the liquid medium may be appropriately selected depending on the type of gel particle stabilizer, etc. For example, when the gel stabilizer is a carboxylic acid compound, the concentration of the gel particle stabilizer in the liquid medium may be 0.1 mM or more and 1 M or less. When the gel stabilizer is a carboxylic acid compound, the concentration of the gel particle stabilizer in the liquid medium may be preferably 10 mM or more, 100 mM or more, 200 mM or more, 300 mM or more, or 400 mM or more, and may be preferably 0.7 M or less, 0.6 M or less, or 0.5 M or less. For example, when the gel stabilizer is a water-soluble organic solvent, the concentration of the gel particle stabilizer in the liquid medium may be 1 vol% or more and 99 vol% or less. When the gel particle stabilizer is a water-soluble organic solvent, the concentration of the gel particle stabilizer in the liquid medium may be preferably 5 vol% or more, 10 vol% or more, 20 vol% or more, 25 vol% or more, or 30 vol% or more, and may be preferably 60 vol% or less, 50 vol% or less, 40 vol% or less, or 35 vol% or less.

[0037] When the mixture includes a liquid medium, the concentration of the gel in the mixture may be, for example, 1% by volume or more and 99% by volume or less, and preferably 10% by volume or more, or 30% by volume or more, and preferably 80% by volume or less, or 70% by volume or less.

[0038] In the dispersion step, shear force is applied to the prepared mixture to obtain gel particles. Examples of methods for applying shear force include a method using a homogenizer, ultrasonic treatment, and a method using a filter mesh.

[0039] The gel particles obtained in the dispersion step may have a number average diameter D50, which is the particle size corresponding to 50% of the cumulative number in the number-based particle size distribution, of 1 μm or more and 500 μm or less. Furthermore, the ratio (D90 / D10) of the D10 particle size, which is the particle size corresponding to 10% of the cumulative number in the particle size distribution, to the D90 particle size, which is the particle size corresponding to 90% of the cumulative number, may be 7 or less. The details of the gel particles obtained in the dispersion step may be the same as those of the 3D printing support material described above.

[0040] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0041] Example 1: 200 mg of gellan gum (GG) powder (trade name: KELCOGEL AFT; manufactured by Sansho Co., Ltd.) was added to 40 mL of phosphate buffered saline (PBS) and dissolved by heating at 100°C for 3 hours to obtain a GG solution. After dissolution, the GG solution was maintained at room temperature for 3 hours to gel. Next, the GG gel was pulverized with a homogenizer for 6 minutes to obtain GG particles.

[0042] 4.2 mL of 0.5 M aqueous trisodium citrate solution was added to 10 mL of the crushed GG particles, and the mixture was homogenized for 6 minutes. The mixture was then centrifuged at 2000 rpm for 3 minutes to remove air bubbles, yielding a support material (0.15 M TSC) for 3D printing.

[0043] (Example 2) A 3D printing support material (0.3 M TSC) was obtained in the same manner as in Example 1, except that a 1 M aqueous solution of trisodium citrate was used and the final concentration of trisodium citrate was adjusted to 0.3 M.

[0044] (Example 3) A 3D printing support material (0.45M TSC) was obtained in the same manner as in Example 1, except that a 1.5M aqueous solution of trisodium citrate was used and the final concentration of trisodium citrate was adjusted to 0.45M.

[0045] (Example 4) A 3D printing support material (0.6M TSC) was obtained in the same manner as in Example 1, except that a 2M aqueous solution of trisodium citrate was used and the final concentration of trisodium citrate was adjusted to 0.6M.

[0046] (Example 5) A 3D printing support material (20% EtOH) was obtained in the same manner as in Example 1, except that 2.5 mL of a 99% aqueous ethanol solution was used instead of the trisodium citrate aqueous solution and the final concentration of ethanol was adjusted to 20%.

[0047] (Example 6) A 3D printing support material (30% EtOH) was obtained in the same manner as in Example 1, except that 4.2 mL of a 99% ethanol aqueous solution was used instead of the trisodium citrate aqueous solution and the final concentration of ethanol was adjusted to 30%.

[0048] (Example 7) A 3D printing support material (ACN) was obtained in the same manner as in Example 1, except that 4.2 mL of a 99% aqueous acetonitrile solution was used instead of the trisodium citrate aqueous solution and the final concentration of acetonitrile was adjusted to 30%.

[0049] (Comparative Example 1) A 3D printing support material (PBS) was obtained in the same manner as in Example 1, except that 4.2 mL of phosphate buffered saline (PBS) was used instead of the trisodium citrate aqueous solution.

[0050] Evaluation 3D printing support material 1 for microscopic observation was obtained in the same manner as in Example 3, except that fluoresceinylglycinamide-modified GG powder was used. Also, 3D printing support material 2 for microscopic observation was obtained in the same manner, using PBS instead of trisodium citrate (TSC) aqueous solution. The obtained 3D printing support material was observed with a confocal laser scanning microscope (CLSM, FV-3000) to obtain microscopic images. The results are shown in Figures 1 and 2.

[0051] The size of the GG particles was measured from the microscopic images obtained above using image analysis software (Image-J) to obtain a particle size distribution based on the number of particles. The results are shown in Figures 3 and 4.

[0052] The particle size distribution was similarly obtained for the 3D printing support materials obtained by adjusting the final ethanol concentration to 20% or 30%. The results are shown in Figures 5 and 6.

[0053] From the particle size distribution obtained above, the number average diameter D50 and the ratio (D90 / D10) were calculated. The results are shown in Table 1.

[0054]

[0055] Preparation of Collagen Ink Collagen powder (manufactured by Nippi Corporation) was added to 0.02 M acetic acid, treated with a homogenizer for 6 minutes, and then maintained at 4° C. for 24 hours to completely dissolve the collagen solution. Air bubbles were removed from the resulting collagen solution by centrifugation at 4,000 rpm for 5 minutes to prepare a collagen ink with a collagen concentration of 10 mg / mL.

[0056] Printing Process 1: Collagen ink was linearly ejected from a 20-gauge nozzle (inner diameter 600 μm) into a bath containing a 3D printing support material at 25°C. The nozzle movement speed was 2 mm / s. The printed collagen fiber in the bath was kept at room temperature for 1 hour to gel. The fiber was removed with tweezers and washed with a 50% ethanol solution to remove GG particles. The resulting fiber was crosslinked by immersion in 0.5% v / v glutaraldehyde in a 50% ethanol solution at 37°C for 24 hours. After crosslinking, the sample was immersed in PBS for 24 hours, washed, and subjected to mechanical testing.

[0057] A microscopic image of a fiber obtained using a 3D printing support material (0.45M TSC) is shown in Figure 7. The change in width of the fiber along its length, measured from the microscopic image, is shown in Figure 8. The average diameter of the obtained fiber was approximately 800 μm. The tensile strength of the obtained fiber after crosslinking was approximately 300 kPa.

[0058] The tensile strength of the crosslinked fiber obtained in the same manner using a 3D printing support material (30% EtOH) was approximately 200 kPa. When a fiber was similarly produced using a 3D printing support material (PBS), it could not be removed from the bath.

[0059] Printing process 1: Using a 3D printer (Bio-X) equipped with a 25-gauge nozzle (inner diameter 260 μm), collagen ink was ejected along a programmed route into a bath containing 3D printing support material (0.3 M TSC) at 25°C to form a 3D structure. The resulting structure is shown in Figures 9A and 9B.

[0060] From the above, it can be seen that high-resolution 3D printing can be achieved by using the 3D printing support material of the present invention as a bath.

[0061] The disclosure of Japanese Patent Application No. 2021-178638 (filing date: November 1, 2021) is incorporated herein by reference in its entirety. All documents, patent applications, and technical standards described herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. gel particles and a gel particle stabilizer, a number average diameter D50, which is a particle diameter corresponding to a cumulative 50% number in a number-based particle size distribution of the gel particles, of 1 μm or more and 500 μm or less; A 3D printing support material in which the ratio (D90 / D10) of D10, which is the particle size corresponding to 10% cumulative number in the particle size distribution, to D90, which is the particle size corresponding to 90% cumulative number, is 7 or less.

2. The support material of claim 1, wherein the gel particles comprise at least one selected from the group consisting of gellan gum, alginic acid, gelatin, collagen, gum arabic, gintan gum, cellulose, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol, starch, and fibrin.

3. 3. The support material according to claim 1, wherein the gel particle stabilizer comprises at least one selected from the group consisting of a carboxylic acid compound, a water-soluble organic solvent, and a salt.

4. providing a mixture comprising a gel and a gel particle stabilizer solution; and applying shear force to the mixture to obtain a gel particle dispersion.

5. 5. The manufacturing method according to claim 4, wherein the gel contains at least one selected from the group consisting of gellan gum, alginic acid, gelatin, collagen, gum arabic, gintan gum, cellulose, hyaluronic acid, laminin, Matrigel (trade name), polyacrylic acid, poly(N-isopropylacrylamide), polymethacrylic acid, polyacrylamide, polystyrene sulfonic acid, polyvinyl alcohol, polyethylene glycol, starch, and fibrin.

6. The method according to claim 4 or 5, wherein the gel particle stabilizer comprises at least one selected from the group consisting of a carboxylic acid compound, a water-soluble organic solvent, and a salt.

7. The gel particles have a number average diameter D50 of 1 μm or more and 500 μm or less, which is a particle diameter corresponding to a cumulative 50% number in a number-based particle size distribution, 6. The method according to claim 4, wherein the ratio (D90 / D10) of D10, which is the particle size corresponding to 10% cumulative number in the particle size distribution, to D90, which is the particle size corresponding to 90% cumulative number, is 7 or less.

8. The gel particles have a number-average diameter D50, which is a particle size corresponding to a cumulative 50% number in a number-based particle size distribution, of 1 μm or more and 500 μm or less, 7. The method according to claim 6, wherein the ratio (D90 / D10) of D10, which is a particle size corresponding to 10% cumulative number in the particle size distribution, to D90, which is a particle size corresponding to 90% cumulative number, is 7 or less.