3D printer and method for manufacturing model

Abstract

To mold a three-dimensional molded object at a high speed.SOLUTION: A three-dimensional printer comprises: coating means for coating a polymer solution containing a polymer material that constitutes a hydrogel to a predetermined thickness; curing means capable of radiating radioactive rays to the coated polymer solution, and capable of forming gel layers by gelatinizing a portion irradiated with the radioactive rays in the polymer solution; and scanning means capable of scanning the curing means with respect to a region coated with the polymer solution. The printer is configured to be able to repeat coating of the polymer solution by the coating means, gelation of the polymer solution by the curing means, and scanning of the curing means by the scanning means, and is configured to be able to mold a molded object by laminating the plurality of gel layers while adhering the gel layers with each other.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a three-dimensional printer, such as a three-dimensional bioprinter, and a method for manufacturing a model. [Background technology]

[0002] Conventionally, there are four known three-dimensional bioprinters: an inkjet type, a dispensing type, a laser transfer type, and a photolithography type (see Non-Patent Document 1). The inkjet type fills a cartridge with bioink, and deforms a print head using a piezoelectric or thermal method to eject ink of a predetermined size. The dispensing type is a type of modeling that uses a single stroke based on a principle similar to the fused deposition modeling (FDM) method, and extrudes ink made of a highly viscous material from a nozzle using air pressure or mechanical drive. The laser transfer type is a type that can transfer cells without contact, and is a type that irradiates a glass substrate having a light absorbing layer with bioink applied on the back side with a pulse laser, concentrating energy at one irradiated point to generate bubbles, which expand and burst, moving the bioink from the glass substrate to the substrate on the printing side, thereby transferring cells without contact. The stereolithography method selectively solidifies bioink on a two-dimensional surface, and has the advantage of fast printing speed. Even if the cell pattern of one layer is complex, it is projected onto the entire surface, so the printing time can be made uniform and printer control can be simplified.

[0003] Furthermore, for example, Patent Document 1 discloses a method for producing a 3D tissue culture model, comprising a first step of printing droplets of bioink on a substrate, a second step of printing droplets of an activator on the bioink droplets to form hydrogel droplets, a third step of repeating the above-mentioned first and second steps in any order to form a hydrogel mold adapted to receive droplets containing cells, a fourth step of printing droplets containing cells on the hydrogel mold, and a fourth step of repeating the first and second steps in any order to form a 3D tissue culture model containing cells encapsulated in the hydrogel mold. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Special Publication No. 2018-522587 [Non-patent literature]

[0005] [Non-Patent Document 1] "3D printing technology increasingly used in medical care" Mizuho Information & Research Institute Report vol.15 2018 Summary of the Invention [Problem to be solved by the invention]

[0006] However, in the above-mentioned conventional techniques, when performing three-dimensional printing (hereinafter referred to as 3D printing), although the modeling speed by the stereolithography method is the fastest, there is a problem that the modeling speed is extremely slow overall. Therefore, a three-dimensional printer that can perform 3D printing at high speed has been desired.

[0007] The present invention has been made in view of the above, and an object of the present invention is to provide a three-dimensional printer and a method for manufacturing a three-dimensional object that can form a three-dimensional object at high speed. [Means for solving the problem]

[0008] In order to solve the above-mentioned problems and achieve the object, a 3D printer according to one embodiment of the present invention comprises a coating means for coating a polymer solution containing a polymer material that constitutes a hydrogel to a predetermined thickness, a hardening means capable of irradiating radiation to the coated polymer solution and gelling the portion of the polymer solution irradiated with the radiation to form a gel layer, and a scanning means capable of scanning the hardening means over the coated area of ​​the polymer solution, and is configured to be capable of repeatedly coating the polymer solution by the coating means, gelling the polymer solution by the hardening means, and scanning the hardening means by the scanning means, and is configured to be capable of forming a model by stacking multiple layers of the gel layers while adhering them to each other.

[0009] A three-dimensional printer according to one aspect of the present invention is characterized in that, in the above invention, a blocking means having a predetermined pattern that blocks at least a portion of the irradiation of the radiation to the applied polymer solution can be arranged between the curing means and the applied polymer solution.

[0010] A three-dimensional printer according to one aspect of the present invention is characterized in that, in the above invention, the polymer solution contains cells, and the three-dimensional printer is a bioprinter configured to be capable of printing cell tissue as the object.

[0011] The three-dimensional printer according to one aspect of the present invention is characterized in that, in the above invention, the radiation is an electron beam.

[0012] The three-dimensional printer according to one aspect of the present invention is characterized in that, in the above invention, the radiation irradiation energy is equal to or greater than 10 keV and equal to or less than 170 keV.

[0013] The three-dimensional printer according to one aspect of the present invention is characterized in that, in the above invention, the predetermined thickness is equal to or greater than 0.01 mm and equal to or less than 1.0 mm.

[0014] A method for manufacturing a molded object according to one aspect of the present invention includes a coating step of coating a polymer solution containing a polymer material that constitutes a hydrogel to a predetermined thickness, a curing step of irradiating the coated polymer solution with radiation emitted from a curing means to gel the portion of the polymer solution that has been irradiated with the radiation and form a gel layer, and a scanning step of scanning the curing means while irradiating the radiation onto the coated area of ​​the polymer solution, wherein the coating step of the polymer solution, the gelling step of the polymer solution, and the scanning step are repeatedly performed to laminate the gel layers together while adhering them to form a molded object.

[0015] A method for manufacturing a molded object according to one aspect of the present invention is characterized in that, in the above-mentioned invention, a blocking means having a predetermined pattern that blocks at least a portion of the irradiation of the radiation to the applied polymer solution is disposed between the curing means and the applied polymer solution.

[0016] In one aspect of the present invention, in the method for manufacturing a shaped object according to the above invention, the polymer solution contains cells, and a cell tissue is modeled as the shaped object.

[0017] In the method for manufacturing a shaped object according to one aspect of the present invention, in the above invention, the radiation emitted by the curing means is an electron beam.

[0018] In the method for manufacturing a shaped object according to one aspect of the present invention, in the above-mentioned invention, the irradiation energy of the radiation is 10 keV or more and 170 keV or less.

[0019] In the method for manufacturing a shaped object according to one aspect of the present invention, in the above-mentioned invention, the predetermined thickness is 0.01 mm or more and 1.0 mm or less. Effect of the Invention

[0020] According to the three-dimensional printer and the method for manufacturing a model according to the present invention, it is possible to manufacture a three-dimensional model at high speed. [Brief description of the drawings]

[0021] [Figure 1] FIG. 1 is a schematic diagram showing a schematic configuration of a 3D bioprinter according to one embodiment of the present invention. [Diagram 2] FIG. 2 is a schematic side view of a 3D bioprinter according to one embodiment of the present invention. [Diagram 3] FIG. 3 is a graph showing the relationship between the absorbed dose and penetration depth of an electron beam produced by a 3D bioprinter according to an embodiment of the present invention. [Figure 4] FIG. 4 is a graph showing the relationship between irradiation energy and penetration depth by a 3D bioprinter according to one embodiment of the present invention. [Diagram 5] FIG. 5 is a graph showing the gel fraction versus the electron beam irradiation dose of a model produced by a 3D bioprinter according to one embodiment of the present invention. [Figure 6] FIG. 6 is a graph showing the elastic modulus versus exposure dose in a model produced by a 3D bioprinter according to one embodiment of the present invention. [Figure 7] FIG. 7 is a graph showing the elastic modulus of a biological composition. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. In all the drawings of the embodiment, the same or corresponding parts are denoted by the same reference numerals. Furthermore, the present invention is not limited to the embodiment described below.

[0023] (3D bioprinter) First, a 3D bioprinter according to an embodiment of the present invention will be described. Fig. 1 is a schematic diagram showing a schematic configuration of a 3D bioprinter according to an embodiment.

[0024] As shown in FIG. 1, a 3D bioprinter 1 according to an embodiment includes an electron beam irradiation unit 11 and a gel solution supply unit 12 having a supply nozzle 12a as a coating unit. A support 13 for supporting a gel-like portion 21 made of hydrogel is provided on the electron beam irradiation side of the electron beam irradiation unit 11 as a curing unit. The support 13 may be configured to be transportable at a speed v or to be step-movable at an average speed v. When a 3D model (hereinafter, model) produced by the 3D bioprinter 1 is composed of only the gel-like portion 21, a material to which the gel-like portion 21 does not adhere is selected as the material of the support 13 in order to peel the support 13 from the gel-like portion 21. On the other hand, when the support 13 is used as a part of the model or the gel-like portion 21 is adhered to the support 13, a material to which the gel-like portion 21 easily adheres is selected as the material of the support 13.

[0025] A lamination unit 14 for laminating the gel into multiple layers is provided on the support 13. The lamination unit 14 is an area determination means for restricting the solution before gelation to a predetermined area. The 3D bioprinter 1 is also configured so that an electron beam mask 3 can be placed above the lamination unit 14. The electron beam mask 3 is made of, for example, a mesh or a dot film, and is configured so as to be able to partially block the irradiation of the electron beam to the gel portion 21.

[0026] As the solute of the solution before gelation according to the present embodiment, various polymeric materials that can be crosslinked and gelled by radiation such as electron beams can be used. Specific examples of the polymeric materials that can be used include polyvinyl alcohol (PVA) resins such as Poval and Exeval (registered trademark) (manufactured by Kuraray Co., Ltd.).

[0027] In addition to the above-mentioned materials, examples of cellulose-based polymeric materials include hypromellose, hydroxypropyl cellulose (low to high molecular weight), sodium carboxymethyl cellulose, and methyl cellulose. Examples of polymeric materials made of water-soluble synthetic resins include polyvinyl alcohol and polyethylene oxide (low to high molecular weight). Examples of sugar chain polymeric materials include κ (kappa) or ι (iota) carrageenan and sodium alginate. Examples of polymeric materials include acrylic acid and polyvinylpyrrolidone (PVP) (low to high molecular weight). Examples of the solvent of the solution before gelation include water, but are not necessarily limited to water.

[0028] In addition, in this embodiment, the 3D bioprinter 1 is described as an example of a three-dimensional printer, but in the case of the 3D bioprinter 1, it is possible to add predetermined cells to be contained in the model to an aqueous solution of a polymer material, i.e., a polymer solution. Various types of cells can be used depending on the model. In other words, the solution used in this embodiment can be a cell-containing solution (hereinafter, bioink), which is a biocompatible solution in which a water-soluble polymer material and predetermined cells are mixed as a solute.

[0029] (Method of manufacturing a molded object) Next, a method for producing a modeled object using the 3D bioprinter 1 according to this embodiment, that is, 3D bioprinting, will be described. Fig. 2 is a side view of the 3D bioprinter 1 for explaining the method for producing a modeled object.

[0030] As shown in FIG. 2, first, a coating step is performed in which the above-mentioned bio-ink 211 is dropped from the supply nozzle 12a onto the bottom surface in the laminated portion 14, i.e., onto the surface of the support 13. Here, the bio-ink 211 is typically applied to a thickness of, for example, 0.01 mm to 1.5 mm, preferably 0.01 mm to 0.5 mm, and more preferably 0.01 mm (10 μm) to 0.1 mm (100 μm) by one drop. The coating thickness of the bio-ink 211 is selected appropriately for each layer, taking into consideration the productivity for the structure and thickness of the shaped object to be manufactured. The coating thickness of the bio-ink 211 is specifically adjusted by a predetermined control unit (not shown) so that, for example, the number of layers is in the range of 10 to 100 layers.

[0031] The coating thickness may be made uniform by rotating the support 13 during dropping (spin coating method) or by scanning a blade plate after dropping (blade method). The bio-ink 211 may be applied to the entire surface of the support 13 without providing the laminated portion 14. Furthermore, in addition to the above-mentioned methods, various methods such as a dipping method and a precipitation method may be used as long as they can make the coating thickness uniform at a predetermined thickness.

[0032] Next, in the irradiation step, the electron beam irradiation unit 11 irradiates the bio-ink 211 in the laminated unit 14 with an electron beam at a predetermined irradiation energy and a predetermined irradiation amount. The irradiation energy and the irradiation amount will be described in detail later.

[0033] In addition, in the scanning step, the electron beam irradiation unit 11 is scanned by a predetermined driving device (not shown) as a scanning means, while irradiating the bio-ink 211 in the stacking unit 14 with an electron beam. Here, the scanning speed V is, for example, about 1 to 10 m / min, but is not limited thereto. Note that the electron beam scanning may be performed by fixing the electron beam irradiation unit 11 and moving the support 13 and the stacking unit 14 using a driving unit (not shown) that moves the support 13 and the stacking unit 14 at a speed v as an operating means. Furthermore, a plurality of driving units may be used as an operating means to relatively move the electron beam irradiation unit 11, the support 13, and the stacking unit 14. In this case, the relative speed between the electron beam irradiation unit 11, the support 13, and the stacking unit 14 may be, for example, about 1 to 10 m / min.

[0034] The electron beam emitted from the electron beam irradiation unit 11 is partially masked by the electron beam mask 3 as a blocking means, and at least a part of the electron beam is selectively irradiated to the bio-ink 211. The electron beam mask 3 has a predetermined mask pattern, and is arranged between the electron beam irradiation unit 11 and the bio-ink 211 after the bio-ink 211 is applied and before the electron beam is irradiated by the electron beam irradiation unit 11. In the bio-ink 211 selectively irradiated with the electron beam by the arrangement of the electron beam mask 3, molecular bonds are broken by the irradiation energy of the electron beam in the polymer material of the part irradiated with the electron beam. In addition, active sites (radicals) are generated in the irradiated part, and the radicals react between molecular chains, causing a crosslinking reaction that forms bonds. As a result, in the bio-ink 211, a crosslinking reaction occurs in the polymer material contained in the part irradiated with the electron beam, gelling, and a curing process is performed in which the part corresponding to the mask pattern is cured. This curing process forms a gel-like layer such as a hydrogel (hereinafter, a gel layer). At approximately the same time, sterilization by the electron beam (electron beam sterilization) is performed on the portion of the applied bio-ink 211 that has been irradiated with the electron beam.

[0035] The lamination process is performed by sequentially repeating the application of the bio-ink 211, the arrangement of the electron beam mask 3 with a predetermined mask pattern, and the irradiation of the electron beam multiple times. In the lamination process, a gel-like portion 21 having a laminated structure in which multiple gel layers 21a, 21b are laminated in the laminate portion 14 is formed. The dropping of the bio-ink 211 and the irradiation of the electron beam may be repeated two or more times, and may be performed various times as long as it is necessary to perform the process multiple times to produce a desired shaped object.

[0036] Here, the effect of irradiation of the electron beam on the bioink 211 will be described. Fig. 3 is a graph showing the relationship between the absorbed dose and the penetration depth for each irradiation energy of the electron beam in the 3D bioprinter 1 according to this embodiment. Note that the graph shown in Fig. 3 shows the case where the electron beam is irradiated to water or an aqueous solution, and the absorbed dose is a relative value. Fig. 4 is a graph showing the relationship between the irradiation energy and the penetration depth in the 3D bioprinter 1 according to this embodiment.

[0037] As shown in FIG. 3 and FIG. 4, when the irradiation energy of the electron beam is 10 keV, the penetration depth of the electron beam is about 10 μm, and the absorbed dose increases from the liquid surface and reaches a maximum at a depth of about 5 μm. The penetration depth is the depth at which the absorbed dose is 10% (0.1) of the peak dose. When the irradiation energy of the electron beam is 30 keV, the penetration depth of the electron beam is about 20 μm, and the absorbed dose increases from the liquid surface and reaches a maximum at a depth of about 7 μm. That is, when the irradiation energy of the electron beam is increased, the penetration depth and the depth at which the absorbed dose reaches a maximum increase. When the irradiation energy of the electron beam is successively set to 50 keV, 60 keV, 70 keV, and 170 keV, the penetration depth of the electron beam and the depth at which the absorbed dose reaches a maximum increase with the increase in irradiation energy. In this way, the absorbed dose has a mountain-shaped distribution (hereinafter, mountain-shaped distribution) that reaches a maximum at a predetermined depth from the irradiated upper surface and becomes lower before and after this predetermined depth.

[0038] The absorbed dose corresponds to the energy distribution given to a liquid such as water (specific gravity is 1). It is considered that even if a liquid, solution, or solvent other than water is used, the dose and penetration depth distribution will have a relatively similar tendency to the graph shown in Figure 3. Similarly, even if a liquid, solution, or solvent other than water is used, the relationship between irradiation energy and penetration depth will have a similar tendency to the graph shown in Figure 4.

[0039] According to the inventor's findings, the penetration depth is inversely proportional to the specific gravity. Therefore, the unit of the penetration depth on the horizontal axis is changed from μm to g / m 2 The distribution can be calculated by changing the setting. Note that the electron beam irradiation unit 11 may be affected by energy attenuation or scattering depending on the scanning, area irradiation, etc. method, the electron beam extraction window and the distance from the window to the irradiation unit, the gas, etc. Therefore, since the absolute value and distribution of the irradiation energy differ depending on the equipment conditions, it is preferable to control the irradiation energy and film thickness conditions to be appropriate for the equipment conditions.

[0040] Specifically, the resolution required for stacking the gel layers 21a, 21b as the 3D bioprinter 1 is about 10 μm or more and 100 μm or less. This is based on four conventional methods: the inkjet method, the dispensing method, the laser transfer method, and the photo-fabrication method. That is, in the case of the laser transfer method, the resolution is about 10 μm. In the case of the inkjet method, the resolution is about 50 μm. In the case of the dispensing method or the photo-fabrication method, the resolution is about 100 μm. Therefore, in the case of stacking the gel layers 21a, 21b, a resolution of about 10 μm or more and 100 μm or less is considered to be sufficient as a 3D printer.

[0041] Here, the resolution in the 3D bioprinter 1 is equivalent to the penetration depth of the electron beam into the bioink 211. From FIG. 3 and FIG. 4, it can be seen that, with respect to the electron beam, even when the irradiation energy is set to 85 keV, the penetration depth is about 100 μm, which is small and shallow. In addition, in order to selectively harden the applied bioink 211 by the amount of the applied thickness, it is preferable that the applied thickness is approximately the same as the penetration depth. Therefore, it is preferable that the applied thickness of the bioink 211 is determined based on the resolution. Furthermore, from FIG. 3 and FIG. 4, the penetration depth, that is, the resolution, is based on the irradiation energy of the electron beam irradiated from the electron beam irradiation unit 11. Therefore, when the resolution in the 3D bioprinter 1 is set to 10 to 100 μm, it is preferable that the irradiation energy by the electron beam irradiation unit 11 is set to 10 keV or more and 85 eV or less from FIG. 4.

[0042] The polymeric material and solvent for the gel used in this embodiment have a specific gravity of 1.0 to 2.0, preferably 1.0 to 1.5. As described above, the penetration depth is inversely proportional to the specific gravity, so that the irradiation energy is typically selected to be 170 keV or less, preferably 125 keV or less, taking the specific gravity into consideration.

[0043] In this way, since there is little need to increase the irradiation energy, the electron beam irradiation unit 11 in the 3D bioprinter 1 can be made smaller, and a shielding mechanism (not shown) for preventing leakage of the electron beam can be simplified, thereby reducing costs. Furthermore, since the irradiation energy can be suppressed, thermal damage to the solution can be reduced. In addition, since the irradiation of the electron beam can provide a sterilization or disinfection effect, a so-called clean process can be realized.

[0044] According to the findings of the present inventors, the gel fraction increases in response to an increase in the irradiation dose of the electron beam from the electron beam irradiation unit 11. FIG. 5 is a graph showing an example of the relationship between the electron beam irradiation dose (kGy) and the gel fraction (%) in the 3D bioprinter according to this embodiment. It can be seen from FIG. 5 that the gel fraction increases smoothly as the electron beam irradiation dose is increased. This shows that the gelation rate of the gel-like portion 21 can be adjusted by controlling the irradiation dose of the electron beam, and the hardness, i.e., the elastic modulus, of the manufactured object can be adjusted.

[0045] Fig. 6 is a graph showing the tendency of the elastic modulus with respect to the irradiation dose in a model produced by the 3D bioprinter 1 according to this embodiment. Fig. 7 is a graph showing the elastic modulus of a biological composition.

[0046] As shown in FIG. 6, the elastic modulus of a model produced using the 3D bioprinter 1 increases with an increase in the dose of electron beam irradiation. This allows the elastic modulus of the model to be adjusted by controlling the dose of electron beam irradiation to the applied bioink 211. From FIG. 6, it can be seen that the hardness, i.e., elastic modulus of a model produced by the 3D bioprinter 1 is up to about 500 kPa (0.5 MPa). Comparing the graph shown in FIG. 6 with the elastic modulus of various cells shown in FIG. 7, it can be seen that the 3D bioprinter 1 according to this embodiment can generate biological tissues up to the level of osteoblasts as models, and can generate various soft tissues and cartilage tissues.

[0047] In addition, in order to prevent cell death due to electron beam irradiation, it is possible to adjust the electron beam energy, adjust the parameters so that the energy at the deepest part is kept at a few kGy or less and more than 10% remains, form irradiated and unirradiated areas by irradiating the electron beam in pulses, or protect cells by impregnating them into clusters of metal nanoparticles.

[0048] Conventionally, the modeling speed of 3D bioprinters using the four methods mentioned above is very slow, and even the fastest modeling method, the stereolithography method, is desired to be improved. This stereolithography method has the problem that the properties of the forming material are restricted because the type and amount of the hardener and light absorber added to the bioink are adjusted to form a gel. In addition, there is a problem that cells die when the irradiation amount or the amount of hardener or light absorber is increased to increase the speed or make the film thinner. Furthermore, there are problems with the use of ultraviolet light and cytotoxicity (cell damage) caused by residual hardener and absorber.

[0049] In contrast, in the embodiment described above, the 3D bioprinter 1 can instantly gel the bioink 211 containing a polymeric material by irradiating it with an electron beam through electron beam crosslinking, thereby speeding up the generation of the model. Furthermore, by adjusting the voltage and current for irradiating the electron beam, the amount of irradiation of the electron beam can be varied, and the gelation rate of the bioink 211, i.e., the hardness and the film thickness depending on the amount of the bioink 211 applied can be adjusted, so that the hardness and film thickness of the gelled portion 21 can be freely controlled. Furthermore, the electron beam mask 3 having a predetermined pattern can form irradiated and non-irradiated portions in the bioink 211 in a desired pattern. Therefore, it is possible to rapidly mold three-dimensional fine and highly functional structures such as nutrient perfusion channels and blood vessel formation introduction channels. Furthermore, since no cytotoxic crosslinking agents or light absorbing materials remain, the irradiated portions are sterilized by the electron beam, while cultured cells can remain in the non-irradiated portions.

[0050] Although the embodiment of the present invention has been specifically described above, the present invention is not limited to the above-mentioned embodiment, and various modifications based on the technical idea of ​​the present invention are possible. For example, the numerical values ​​given in the above-mentioned embodiment are merely examples, and numerical values ​​different from these may be used as necessary, and the present invention is not limited by the description and drawings that form a part of the disclosure of the present invention according to the present embodiment.

[0051] For example, in the above-described embodiment, depending on the type of polymer material of the gel-like portion 21 to be hardened, a radiation irradiation unit capable of irradiating radiation such as gamma rays or a laser light irradiation unit capable of irradiating laser light may be used instead of the electron beam irradiation unit 11. Note that radiation includes particle radiation such as alpha rays, beta rays (electron beams), neutron beams, proton beams, heavy ion beams, and meson beams, which are material particles that flow with high kinetic energy, and electromagnetic radiation such as high-energy electromagnetic waves (gamma rays and X-rays).

[0052] For example, in the embodiment described above, the desired portions of the bioink 211 are selectively cured using an electron beam mask 3 having a predetermined mask pattern, but it is not necessary to use an electron beam mask. It is also possible to limit the area to be irradiated from the electron beam irradiation unit 11 and repeatedly turn on and off the emission of the electron beam, i.e., turn on and off spot irradiation while scanning, or to use the electron beam mask 3 in combination with turn on and off irradiation while scanning.

[0053] The 3D bioprinter 1 according to the embodiment described above can realize not only the formation of any cell type from spheroid cells by adjusting the gel fraction, but also culture by forming a microchannel for perfusion in three dimensions, and the production of organs from diverse cellular tissues by layering multiple types of cell sheets on tissues consisting of various cells.

[0054] In addition, in the embodiment described above, a model is manufactured by layering the bio-ink 211, which is a cell-containing solution, as gel layers 21a, 21b. However, it is also possible to use a solution that contains a polymeric material but does not contain cells to form a scaffold material with, for example, a blood vessel-like flow path in the part that is not gelled by the electron beam mask 3 described above, and then flow a solution into this flow path to introduce and impregnate cells by capillary action. [Explanation of symbols]

[0055] 1. 3D bioprinter 3 Electron Beam Mask 11 Electron beam irradiation unit 12 Gel solution supply unit 12a Supply nozzle 13 Support 14 Laminated section 21 Gel-like portion 21a, 21b Gel layer 211 Bioink

Claims

1. A coating means for coating a polymer solution containing cells and a polymer material constituting a hydrogel to a predetermined thickness; a curing means capable of irradiating the applied polymer solution with radiation by adjusting an output amount by adjusting a voltage or a current, and capable of gelling a portion of the polymer solution irradiated with the radiation to form a gel layer; a scanning means capable of scanning the curing means over the area where the polymer solution is applied, The coating of the polymer solution by the coating means, the gelation of the polymer solution by the hardening means, and the scanning of the hardening means by the scanning means can be repeatedly performed, The gel layers are laminated in multiple layers while being bonded to each other, thereby enabling a modeled object to be formed, The object is a biological tissue composed of the cells, and the radiation dose is set to be larger as the elastic modulus required for the biological tissue is larger. A three-dimensional printer characterized by:

2. The coating means coats the polymer solution having a specific gravity of 1.0 to 2.0 to a thickness of 0.01 mm to 1.0 mm, The radiation is an electron beam having an irradiation energy of 10 keV or more and 170 keV or less.

2. The three-dimensional printer according to claim 1.

3. The specific gravity of the polymer solution is 1.5 or less, The irradiation energy of the electron beam is 125 keV or less.

3. The three-dimensional printer according to claim 2.

4. A blocking means having a predetermined pattern for blocking at least a part of the irradiation of the radiation to the applied polymer solution can be disposed between the curing means and the applied polymer solution.

4. The three-dimensional printer according to claim 1, wherein the three-dimensional printer is a three-dimensional printer.

5. A coating process for coating a polymer solution containing cells and a polymer material constituting a hydrogel to a predetermined thickness; a curing step of irradiating the applied polymer solution with radiation emitted from a curing means capable of adjusting the amount of radiation emitted by adjusting a voltage or a current to gel the portion of the polymer solution irradiated with the radiation to form a gel layer; a scanning step of scanning the curing means while irradiating the radiation onto the area where the polymer solution is applied, Repeating the application of the polymer solution in the application step, the gelation of the polymer solution in the curing step, and the scanning step; forming a shaped object by laminating a plurality of the gel layers while adhering them to each other; The object is a biological tissue composed of the cells, and the radiation dose is set to be larger as the elastic modulus required for the biological tissue is larger. A method for manufacturing a shaped object comprising the steps of:

6. In the coating step, the polymer solution having a specific gravity of 1.0 to 2.0 is coated to a thickness of 0.01 mm to 1.0 mm, The radiation is an electron beam having an irradiation energy of 10 keV or more and 170 keV or less. The method for manufacturing a shaped object according to claim 5 .

7. The specific gravity of the polymer solution is 1.5 or less, The irradiation energy of the electron beam is 125 keV or less. The method for manufacturing a shaped object according to claim 6 .

8. A blocking means having a predetermined pattern for blocking at least a part of the irradiation of the radiation to the applied polymer solution is disposed between the curing means and the applied polymer solution. The method for manufacturing a shaped object according to any one of claims 5 to 7.

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