JP2018035271A - Hydrogel structure, and production method and use of the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hydrogel structure giving a feeling similar to that of an actual blood vessel or the like when medical equipment such as a catheter is inserted and reproducing a plurality of organs of different hardness.SOLUTION: A hydrogel structure containing water and a polymer has a hollow tube shape and satisfies at least one of the following (1) and (2). (1) At least a part of the hollow tube shape contacts a hydrogel having an elastic modulus different from that of a hydrogel constituting the hollow tube shape. (2) The hollow tube shape is composed of at least two kinds of hydrogel having a different elastic modulus.SELECTED DRAWING: None

Description

  The present invention relates to a hydrogel structure, and a production method and use thereof.

Vascular treatment mainly includes treatment of aneurysms (aneurysms), bypass of blood vessels, cutting, and anastomosis.
These vascular treatments are often performed by inserting a catheter, which is a wire-shaped instrument, into the blood vessel. Regarding the catheter intubation, it is necessary to perform a technique training. However, when the human body is not used, the technique training is performed using an animal other than a human or a blood vessel model.

However, in the technique training, when a non-human animal is used, the blood vessel exists in the body, and therefore, the catheter is intubated by irradiating the affected part with X-rays to visualize the blood vessel. Therefore, when the technique training is repeatedly performed, there is a problem that the operator's X-ray exposure increases.
Therefore, a catheter treatment simulator formed of a transparent material has been proposed (see, for example, Patent Document 1).

  Further, it is used for a blood vessel model imitating a patient's blood vessel (for example, see Patent Document 2), a blood vessel lesion model formed from a plurality of small lesions having different hardness (for example, see Patent Document 3), and preoperative simulation. A method for manufacturing a blood vessel model (see, for example, Patent Document 4) and a block-shaped blood vessel model in which the outer surface of a simulated blood vessel wall is surrounded by an elastic base material different from that of the simulated blood vessel wall (for example, see Patent Document 5) are proposed. ing.

  It is an object of the present invention to provide a hydrogel structure that reproduces a plurality of sites that have a texture similar to that of an actual blood vessel when inserted into a medical device such as a catheter and that have different hardnesses.

The hydrogel structure of the present invention as a means for solving the problems includes water and a polymer, has a hollow tube shape, and satisfies at least one of the following (1) to (2).
(1) At least a part of the hollow tube shape is in contact with a hydrogel having an elastic modulus different from that of the hydrogel constituting the hollow tube. (2) At least two types of the hollow tube shape having different elastic moduli. Formed by hydrogel

  ADVANTAGE OF THE INVENTION According to this invention, the hydrogel structure which reproduced the several site | part with which the texture at the time of insertion of medical devices, such as a catheter, is close to an actual blood vessel etc., and hardness differs can be provided.

FIG. 1 is a schematic view showing an example of the hydrogel structure of the present invention. FIG. 2 is a schematic view showing another example of the hydrogel structure of the present invention. FIG. 3A is a schematic top view showing an example of a structure to which a transparent hard body is attached. FIG. 3B is a schematic side view showing an example of a structure to which a transparent hard body is attached. FIG. 4 is a schematic view showing an example of a manufacturing process of a molded body using a three-dimensional modeling apparatus used in the method for manufacturing a hydrogel structure of the present invention. FIG. 5 is a schematic view showing an example of a three-dimensional modeling apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 6 is a schematic view showing an example of mixing the first liquid and the second liquid by the droplet discharge method. FIG. 7 is a schematic view showing an organ model whose outer shape is similar to that of an organ (liver) as an embodiment of the hydrogel structure of the present invention.

(Hydrogel structure, blood vessel model, and organ model)
The hydrogel structure of the present invention contains water and a polymer, has a hollow tube shape, and satisfies at least one of the following (1) to (2).
(1) At least a part of the hollow tube shape is in contact with a hydrogel having an elastic modulus different from that of the hydrogel constituting the hollow tube. (2) At least two types of the hollow tube shape having different elastic moduli. The hydrogel structure formed by a hydrogel further includes a mineral, and the hydrogel includes the water in a three-dimensional network structure formed by combining the polymer and the mineral. Preferably there is. In addition, the said hydrogel means the gel which contains water as a main component.
In the conventional catheter treatment simulator, the hydrogel structure of the present invention has a problem that the manufacturing method is limited from the materials to be used, and the hydrogel structure cannot be applied to 3D printing capable of reproducing complicated shapes and shapes in accordance with patient personal data. In addition, the created blood vessel model can only be placed on a two-dimensional plane and cannot reproduce an actual three-dimensional solid structure. For preoperative simulation for treating an affected part of a three-dimensional structure, It is also based on the knowledge that there is a problem that it cannot be applied.
The hydrogel structure of the present invention is produced by three-dimensional modeling of a flexible material such as silicone rubber in the conventional blood vessel model, but it is an opaque model and has a texture that is similar to that of an actual blood vessel. Is based on the knowledge that there is a problem of different.
Furthermore, the hydrogel structure of the present invention has a problem that a plurality of materials are required to form a plurality of small lesions having different hardnesses in the conventional vascular lesion model. In addition, it is based on the knowledge that modeling based on patient personal data is difficult due to modeling by a mold, and it is difficult to reproduce a detailed structure.
Furthermore, the hydrogel structure of the present invention can form a complex shape to some extent by the conventional method for producing a blood vessel model, but the blood vessel model does not have a high transmittance, and the texture is similar to that of an actual blood vessel. Is based on the knowledge that there is a problem of different.
Furthermore, the hydrogel structure of the present invention is based on the knowledge that it is difficult to reproduce the fine structure of the simulated blood vessel wall in the conventional block-shaped blood vessel model, and the manufacturing method is complicated.

The blood vessel model of the present invention comprises the hydrogel structure of the present invention.
There is no restriction | limiting in particular as said blood vessel model, Although it can select suitably according to the objective, What reproduced this based on the blood vessel shape of the site | part used as a patient's treatment object is preferable.
The organ model of the present invention is composed of the hydrogel structure of the present invention, and its outer shape is a shape imitating an organ shape.

  The hydrogel structure, blood vessel model, and organ model of the present invention can be suitably used for catheter intubation technique training or preoperative simulation.

In the hydrogel structure of the present invention, for example, the distal end portion of the hollow tube may be narrowed, the intermediate portion may be narrowed, and one end opening may be narrower than the other end opening. Moreover, it may be branched or dendritic and is preferably vascular.
As said structure, you may communicate, you may have a blockade in a part of pipe | tube, and the terminal may close. The hollow tube may be a double tube or may be laminated.

  Examples of the shape of the hollow tube include blood vessels, lymph vessels, esophagus, nasal cavity, ear canal, pharynx, larynx, oral cavity, trachea, bronchi, bronchiole, stomach, small intestine (eg, duodenum, jejunum, ileum, etc.), large intestine ( For example, the cecum, colon, rectum, anal canal, etc.), pancreatic duct, gallbladder duct, urethra, bile duct, etc. can be used for various pre-operative simulations and procedure exercises.

The hydrogel structure having the blood vessel shape can be suitably used as a blood vessel model.
There is no restriction | limiting in particular as said blood vessel model, According to the objective, it can select suitably, For example, what reproduced the artery, the vein, the capillary, etc. is mentioned.

FIG. 1 is a schematic view showing an example of the hydrogel structure of the present invention. As shown in FIG. 1, a second hydrogel 53 having an elastic modulus different from that of the first hydrogel around a blood vessel model 52 having a blood vessel cavity 50 and a blood vessel wall 51 made of the first hydrogel. By making the structure covered with the above, it is possible to reproduce a texture close to that of a blood vessel in contact with an actual organ.
FIG. 2 is a schematic view showing another example of the hydrogel structure of the present invention. As shown in FIG. 2, a part such as an aneurysm 55 having a lower elastic modulus than a normal normal blood vessel is added to a blood vessel model having a blood vessel cavity 50 and a blood vessel wall 51 made of a first hydrogel. The vascular lesion model can also be reproduced by reproducing with a second hydrogel having an elastic modulus different from that of the first hydrogel.
In addition, a blood vessel model having a blood vessel wall portion composed of at least a first hydrogel and a second hydrogel can be produced, and thereby the texture of a blood vessel hardened due to a disease or the like can be reproduced.

  As the hydrogel structure, in order to allow a liquid simulating blood to flow in the blood vessel model, a liquid inflow / outlet port may be provided and a liquid circulation device may be attached.

  Moreover, the said other hydrogel 53 may have the external shape imitating an organ, and can be used suitably as an organ model.

  The organ model is not particularly limited and can be appropriately selected according to the purpose, and can reproduce all internal organs in the human body. For example, the brain, heart, bladder, as shown in FIG. Liver, kidney, pancreas, spleen, gallbladder, uterus and the like.

The hydrogel structure satisfies at least one of (1) to (2).
In the case of (1), in the hollow tube shape, it is possible to reproduce a texture very close to that of a hollow tube such as an actual blood vessel.
Further, in the case of (2), a vascular lesion model having an aneurysm in a hollow tube shape can be formed.

The elastic modulus of the hydrogel structure having the hollow tube shape (the blood vessel model 52 in FIGS. 1 and 2) is preferably 0.1 MPa or more and 0.5 MPa or less, more preferably 0.1 MPa or more and 0.25 MPa or less. preferable. The elastic modulus is the compressive strength at 20% compression.
The compressive strength at the time of 70% compression of the hydrogel structure having the hollow tube shape (the blood vessel model 52 in FIGS. 1 and 2) is preferably 0.1 MPa or more and 1 MPa or less, and 0.1 MPa or more and 0.7 MPa. The following is more preferable.

At least a part of the hydrogel (1) (second hydrogel 53 in FIG. 1) or another hydrogel (2) (FIG. 2) having an elastic modulus different from that of the hydrogel structure. The elastic modulus of the knob portion 55) is preferably 0.005 MPa or more and 0.1 MPa or less, and more preferably 0.01 MPa or more and 0.05 MPa or less.
At least a part of the hydrogel (1) (second hydrogel 53 in FIG. 1) or another hydrogel (2) (FIG. 2) having an elastic modulus different from that of the hydrogel structure. The compressive strength at the time of 70% compression of the knob portion 55) is preferably 0.3 MPa or more and 1 MPa or less, and more preferably 0.4 MPa or more and 0.7 MPa or less.
The elastic modulus and the compressive strength at the time of 70% compression were measured using a universal testing machine (manufactured by Shimadzu Corporation, AG-I), a load cell 1 kN, 1 kN compression jig for a 1 mm diameter circle. The columnar metal is pushed into a hydrogel structure containing water as a main component, the stress against compression applied to the load cell is recorded in a computer, the stress against displacement is plotted, and the elastic modulus can be measured. The elastic modulus can be controlled by adjusting the water content of the hydrogel structure and a hydrogel (another hydrogel structure) having an elastic modulus different from that of the hydrogel structure.

  When the elastic modulus of one part in the hydrogel structure in (2) is X (MPa) and the elastic modulus of another part adjacent to the one part is Y (MPa), the absolute change in elastic modulus The value (| X−Y |) is 0.1 MPa or more, preferably 0.11 MPa or more. When the absolute value of the elastic modulus change (| X−Y |) is 0.1 MPa or more, the elastic modulus is different in the same hydrogel structure, so that it is more than a normal blood vessel such as an aneurysm in the blood vessel. The texture of the vascular lesion model as shown in FIG. 2 having a portion having a low elastic modulus can be realized.

The water content of the hydrogel structure having the hollow tube shape is different from that of the hydrogel structure by being lower than the water content of the hydrogel having an elastic modulus different from that of the hydrogel structure. The elastic modulus of the hydrogel structure can be made higher than the elastic modulus of the hydrogel having water, which is superior to the reproducibility of the actual blood vessel texture.
There is no restriction | limiting in particular as a moisture content of the hydrogel structure which has the said hollow tube shape, Although it can select suitably according to the objective, 30 to 75 mass% is preferable.
There is no restriction | limiting in particular as a moisture content of the hydrogel which has a different elastic modulus from the said hydrogel structure, Although it can select suitably according to the objective, 50 to 90 mass% is preferable.
The moisture content can be measured using, for example, a heat drying moisture meter (device name: MS-70, manufactured by A & D Co., Ltd.).

The transmittance of the hydrogel structure in the visible light region is preferably 80% or more, more preferably 85% or more, still more preferably 90% or more, and particularly preferably 95% or more. When the transmittance is 80% or more, the inside of the hydrogel structure can be visualized. The transmittance can be measured using, for example, a spectrophotometer (device name: UV-3100, manufactured by Shimadzu Corporation, using an integration unit). The visible light region means a wavelength region having a wavelength of 400 nm or more and 700 nm or less.
As a method for measuring the transmittance, the hydrogel structure is cut in the longitudinal direction to form a flat sample. At this time, in order to prevent irregular reflection due to the influence of the unevenness of the sample surface, the measurement is performed using an integrating sphere unit. Moreover, when measuring a detail, it is also possible to measure using an optical fiber etc.

The 10-point average value of the maximum inner diameter in at least a part of the hydrogel structure is preferably 1.0 mm or less, more preferably 0.5 mm or less, and particularly preferably 0.3 mm or less. The maximum inner diameter can be measured using a digital microscope (device name: VHX-5000, manufactured by Keyence Corporation).
The 10-point average value of the maximum inner diameter is a value measured at a close portion where the outer diameter of the hydrogel structure is the same. In the adjacent part where the outer diameter of the hydrogel structure is the same, when the maximum inner diameter cannot be measured at 10 points, the average value of the points that can be measured is taken. The outer diameter can be measured using a digital microscope (device name: VHX-5000, manufactured by Keyence Corporation).

<Polymer>
There is no restriction | limiting in particular as said polymer, Although it can select suitably according to the objective, Since hydrogel has water as a main component, a water-soluble polymer is preferable. By including the water-soluble polymer, the strength of the hydrogel mainly composed of water can be maintained.
The water solubility of the water-soluble polymer means, for example, that when 1 g of the water-soluble polymer is mixed with 100 g of water at 30 ° C. and stirred, 90% by mass or more of the water-soluble polymer is dissolved.

  Examples of the polymer include polymers having an amide group, amino group, hydroxyl group, tetramethylammonium group, silanol group, epoxy group, and the like.

  The polymer may be a homopolymer (homopolymer), a heteropolymer (copolymer), unmodified, or a known functional group introduced. It may also be in the form of a salt. Among these, a homopolymer is preferable.

  The polymer can be obtained by polymerizing a polymerizable monomer. The said polymerizable monomer is demonstrated in the manufacturing method of the hydrogel structure mentioned later.

  As the water-soluble polymer, a polymerizable monomer is polymerized. Examples of the polymerizable monomer include acrylamide, N-substituted acrylamide derivatives, N, N-disubstituted acrylamide derivatives, N-substituted methacrylamide derivatives, Examples thereof include N, N-disubstituted methacrylamide derivatives. These may be used individually by 1 type and may use 2 or more types together.

  By polymerizing the polymerizable monomer, a water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group, or the like is obtained. The water-soluble polymer having the amide group, amino group, hydroxyl group, tetramethylammonium group, silanol group, epoxy group or the like is an advantageous component for maintaining the strength of the aqueous gel.

  There is no restriction | limiting in particular as content of the said polymer, Although it can select suitably according to the objective, 0.5 mass% or more and 20 mass% or less are preferable with respect to the hydrogel structure whole quantity.

<Mineral>
The mineral is not particularly limited and can be appropriately selected according to the purpose. However, since the hydrogel is mainly composed of water, a layered clay mineral that can be uniformly dispersed at the level of primary crystals in water is obtained. Preferably, a water-swellable layered clay mineral is more preferable.

  The water-swellable layered clay mineral presents a state in which two-dimensional disk-shaped crystals having a unit cell in the crystal are stacked, and when the water-swellable layered clay mineral is dispersed in water, each single-layer state To form a disk-like crystal.

There is no restriction | limiting in particular as said water-swellable clay mineral, According to the objective, it can select suitably, For example, water-swellable smectite, water-swellable mica, etc. are mentioned. These may be used individually by 1 type and may use 2 or more types together. Among these, water-swelling hectorite containing sodium as an interlayer ion, water-swelling montmorillonite, water-swelling saponite, and water-swelling synthetic mica are preferable, and a water-swelling hectorite is obtained from the point that a highly elastic bolus is obtained. More preferred. The water swellability means that water molecules are inserted between layers of the layered clay mineral and dispersed in water.
As said mineral, what was synthesize | combined suitably may be sufficient and a commercial item may be sufficient.

  There is no restriction | limiting in particular as said commercial item, According to the objective, it can select suitably, For example, synthetic hectorite (Laponite XLG, the product made by RockWood), SWN (made by Coop Chemical Ltd.), fluorinated hectorite SWF (Coop Chemical Ltd.) etc. are mentioned. These may be used individually by 1 type and may use 2 or more types together.

  There is no restriction | limiting in particular as content of the said mineral, Although it can select suitably according to the objective, 1 mass% with respect to the hydrogel structure whole quantity from the point of the elasticity modulus and hardness of a hydrogel structure. The content is preferably 40% by mass or less and more preferably 1% by mass or more and 25% by mass or less.

<Organic solvent>
In the present invention, an organic solvent can be added to improve the moisture retention of the hydrogel structure.
Examples of the organic solvent include water-soluble organic solvents. The water solubility of the water-soluble organic solvent means that the organic solvent can be dissolved in water by 30% by mass or more.

  The water-soluble organic solvent is not particularly limited and may be appropriately selected depending on the intended purpose. For example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, sec-butyl alcohol, alkyl alcohols having 1 to 4 carbon atoms such as tert-butyl alcohol; amides such as dimethylformamide and dimethylacetamide; ketones or ketone alcohols such as acetone, methyl ethyl ketone and diacetone alcohol; ethers such as tetrahydrofuran and dioxane; Ethylene glycol, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, 1 Polyhydric alcohols such as 2,6-hexanetriol, thioglycol, hexylene glycol and glycerin; polyalkylene glycols such as polyethylene glycol and polypropylene glycol; ethylene glycol monomethyl (or ethyl) ether, diethylene glycol methyl (or ethyl) ether, Lower alcohol ethers of polyhydric alcohols such as triethylene glycol monomethyl (or ethyl) ether; alkanolamines such as monoethanolamine, diethanolamine, triethanolamine; N-methyl-2-pyrrolidone, 2-pyrrolidone, 1,3 -Dimethyl-2-imidazolidinone and the like. These may be used individually by 1 type and may use 2 or more types together. Among these, from the viewpoint of moisture retention, polyhydric alcohol, glycerin, and propylene glycol are preferable, and glycerin and propylene glycol are more preferable.

  As content of the said organic solvent, 10 mass% or more and 50 mass% or less are preferable with respect to the hydrogel structure whole quantity. When the content is 10% by mass or more, the effect of preventing drying is sufficiently obtained. Moreover, a mineral is disperse | distributed uniformly as it is 50 mass% or less.

<Water>
As said water, pure water, such as ion-exchange water, ultrafiltration water, reverse osmosis water, distilled water, and ultrapure water can be used, for example.
In the water, other components such as an organic solvent may be dissolved or dispersed in accordance with the purpose of imparting moisture retention, imparting antibacterial properties, imparting conductivity, adjusting hardness, and the like.

  The water content is preferably 10% by mass or more and 99% by mass or less, more preferably 50% by mass or more and 98% by mass or less, and particularly preferably 60% by mass or more and 97% by mass or less with respect to the total amount of the hydrogel structure. .

<Other ingredients>
The other components are not particularly limited and may be appropriately selected depending on the purpose. For example, stabilizers, surface treatment agents, polymerization initiators, colorants, viscosity modifiers, adhesion imparting agents, oxidation agents, and the like. Examples thereof include an inhibitor, an antioxidant, a crosslinking accelerator, an ultraviolet absorber, a plasticizer, an antiseptic, a dispersant, and a surfactant.

The hydrogel structure of the present invention preferably has a surface covered with a transparent hard body.
FIG. 3A is a schematic top view showing an example of a hydrogel structure 60 to which a transparent hard body 61 is attached. FIG. 3B is a schematic side view showing an example of a hydrogel structure 60 to which a transparent hard body 61 is attached. As shown in FIG. 3A and FIG. 3B, the surface is covered with a transparent hard body 61, so that the shape of the blood vessel model is maintained and the handling property during the operation and the preservation of the blood vessel model are improved ( The drying resistance and antiseptic properties can be improved (that is, the water vapor permeability and oxygen permeability of the hard body can be reduced), and the appearance of the blood vessel model can be improved.

The material for forming the hard body is not particularly limited and may be appropriately selected depending on the purpose. For example, a highly transparent plastic material such as acrylic resin or polycarbonate resin, or a highly transparent inorganic material such as glass. Etc.
There is no restriction | limiting in particular as a shape and average thickness of the said hard body, According to the objective, it can select suitably.
The water vapor transmission rate is preferably 500 g / m ² · d or less. The water vapor transmission rate can be measured, for example, with a water vapor transmission meter (device name: Lyssy L80, manufactured by Systech) based on JIS K7129.
The oxygen permeability is preferably 100,000 cc / m ² / hr / atm or less. The oxygen permeability can be measured by, for example, a differential pressure type gas permeability meter (device name: Lyssy L100, manufactured by SYSYTECH) based on JIS Z1702.

  As the structure, in order to allow a liquid imitating blood to flow through the blood vessel model, a liquid inflow / outlet port may be provided and a liquid circulation device may be attached.

(Professional practice equipment)
The technique training tool of the present invention has at least one selected from a hydrogel structure, a blood vessel model, and an organ model, and at least one of a catheter and an endoscope, and further includes other members as necessary. Have

  There is no restriction | limiting in particular as said catheter, According to the objective, it can select suitably, For example, a catheter for angiography, a balloon catheter, a cerebral blood vessel catheter, a cancer catheter treatment, a blood vessel indwelling catheter, a suction indwelling catheter, a urethral catheter Etc.

  The endoscope is not particularly limited and may be appropriately selected depending on the intended purpose. For example, the laryngoscope, bronchoscope, upper gastrointestinal endoscope, duodenoscope, small intestine endoscope, large intestine An endoscope, a thoracoscope, a cystoscope, a cholangioscope, a blood vessel endoscope, etc. are mentioned.

The hydrogel structure, blood vessel model, and organ model of the present invention can be used for catheter intubation technique training and simulation before surgery.
The catheter intubation technique training here refers to training a technique for intubating a catheter into a blood vessel model and reaching a target location. In this case, training is also included in which the thickness of the catheter is changed according to the purpose, or a stent, a wire, a balloon or the like is provided at the distal end, and this is treated or installed at the affected site.
Selecting an optimum catheter according to the blood vessel shape is also part of the training, and it is useful to handle one or more catheters and the hydrogel structure of the present invention as a set.

In such training, it is preferable to resemble a state in an actual blood vessel. The blood vessel model or structure of the present invention is composed of a hydrogel and becomes a useful material because its texture is very similar to that of a living body. It is also useful to provide a mechanism for flowing a liquid in the hydrogel structure and train in a state where blood flow is generated.
In the past, since there were few transparent blood vessel models, it was also useful that the training that had been performed by irradiating and visualizing X-rays could be performed without risk of X-ray exposure. .

(Method for producing hydrogel structure)
Although the manufacturing method of the hydrogel structure of the present invention is not particularly limited, for example, a columnar core (support) is formed using a core forming material (support forming material), and the columnar core is A tubular part is formed so as to be covered with the first liquid and the second liquid, and is covered with the first hydrogel and the second hydrogel having an elastic modulus different from that of the first hydrogel. After forming, the columnar core part can be removed to produce the film. At this time, it is preferable to produce by using a layered modeling method such as a conventionally known material jet method (a method of modeling a three-dimensional object by layering by repeating a layer forming step and a layer curing step). In addition, as for the said coating | cover, the said columnar core part should just be covered at least partially by the said hydrogel formation material, and it is preferable that the whole is covered. Moreover, it is preferable that both said core part forming material (support body forming material) and said 1st liquid are active energy ray hardening-type compositions. In addition, the number of repetitions varies depending on the size, shape, structure, etc. of the hydrogel structure to be manufactured, and cannot be specified unconditionally. However, if the average thickness per layer is in the range of 10 μm to 50 μm, the accuracy Well, it is possible to model without peeling.

As a manufacturing method of the hydrogel structure, it is preferable to manufacture a hydrogel structure that satisfies at least one of the following (1) to (2).
(1) At least a part of the hollow tube shape is in contact with a hydrogel having an elastic modulus different from that of the hydrogel constituting the hollow tube. (2) At least two types of the hollow tube shape having different elastic moduli. Formed by hydrogel

  Hereinafter, an example of a method for producing a hydrogel structure by the material jet method will be described in detail.

<< layer forming step and layer forming means >>
The layer forming step is a step of discharging a first liquid and a second liquid containing water and a polymerizable monomer and a support forming material to be removed later to form a layer made of these materials.
The support forming material is applied to a position different from the first liquid and the second liquid, and becomes a support for supporting the hydrogel constituent part after curing. In the present invention, since a hollow tube shape is formed, at the time of lamination, the hollow upper portion is supported by the support. The “position different from the first liquid and the second liquid” means that the application position of the support forming material and the application position of the first liquid and the second liquid do not overlap. In addition, the application position of the support forming material may be adjacent to the application position of the first liquid and the second liquid.

  The method for applying the forming material as the layer forming step is not particularly limited as long as the droplet can be applied to a target place with appropriate accuracy, and can be appropriately selected according to the purpose. , Dispenser method, spray method, ink jet method and the like. In order to carry out these methods, a known apparatus can be suitably used.

  Among these, the dispenser method is excellent in the quantitative property of droplets, but the application area is narrowed, and the spray method can easily form a fine discharge, the application area is wide, and the application property is excellent. The quantitative property of the droplets is poor and scattering due to the spray flow occurs. For this reason, in the present invention, the ink jet method is particularly preferable. The ink jet method is advantageous in that the quantitative property of droplets is better than the spray method, and there is an advantage that the coating area can be widened compared to the dispenser method, and a complicated three-dimensional shape can be formed accurately and efficiently. .

  In the case of the ink jet method, a nozzle capable of discharging the forming material is provided. In addition, as this nozzle, the nozzle in a well-known inkjet printer can be used conveniently.

-Hydrogel forming material (hydrogel precursor)-
The hydrogel-forming material contains water and a polymerizable monomer as the first liquid, preferably contains a mineral and a water-soluble organic solvent, and further contains other components as necessary.
The second liquid is not particularly limited as long as the first liquid can be diluted, and can be appropriately selected according to the purpose. For example, a polymerizable monomer, a water-soluble organic solvent, and, if necessary, polymerization initiation Contains agents and other ingredients.
As said water, the said mineral, the said water-soluble organic solvent, and the said other component, the thing similar to the said hydrogel structure can be used.

--Polymerizable monomer--
The polymerizable monomer is a compound having one or more unsaturated carbon-carbon bonds, and a polymerizable monomer that is polymerized by an active energy ray such as an ultraviolet ray or an electron beam is preferable.
Examples of the polymerizable monomer include a monofunctional monomer and a polyfunctional monomer. These may be used individually by 1 type and may use 2 or more types together.
Examples of the polyfunctional monomer include a bifunctional monomer, a trifunctional monomer, and a tetrafunctional or higher monomer.

  The monofunctional monomer is a compound having one unsaturated carbon-carbon bond. For example, acrylamide, N-substituted acrylamide derivative, N, N-disubstituted acrylamide derivative, N-substituted methacrylamide derivative, N, N -Disubstituted methacrylamide derivatives, other monofunctional monomers and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the N-substituted acrylamide derivative, N, N-disubstituted acrylamide derivative, N-substituted methacrylamide derivative, or N, N-disubstituted methacrylamide derivative include N, N-dimethylacrylamide (DMAA), N- Examples include isopropylacrylamide.

  Examples of the other monofunctional monomers include 2-ethylhexyl (meth) acrylate (EHA), 2-hydroxyethyl (meth) acrylate (HEA), 2-hydroxypropyl (meth) acrylate (HPA), and acryloylmorpholine (ACMO). ), Caprolactone-modified tetrahydrofurfuryl (meth) acrylate, isobornyl (meth) acrylate, 3-methoxybutyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, lauryl (meth) acrylate, 2-phenoxyethyl (meth) acrylate, Isodecyl (meth) acrylate, isooctyl (meth) acrylate, tridecyl (meth) acrylate, caprolactone (meth) acrylate, ethoxylated nonylphenol (meth) acrylate , And the like urethane (meth) acrylate. These may be used individually by 1 type and may use 2 or more types together.

  By polymerizing the monofunctional monomer, a water-soluble polymer having an amide group, amino group, hydroxyl group, tetramethylammonium group, silanol group, epoxy group or the like can be obtained.

  The water-soluble polymer having the amide group, amino group, hydroxyl group, tetramethylammonium group, silanol group, epoxy group or the like is an advantageous component for maintaining the strength of the blood vessel model.

  Examples of the bifunctional monomer include tripropylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, and neopentyl glycol hydroxypivalic acid. Ester di (meth) acrylate (MANDA), hydroxypivalate neopentyl glycol ester di (meth) acrylate (HPNDA), 1,3-butanediol di (meth) acrylate (BGDA), 1,4-butanediol di (meth) Acrylate (BUDA), 1,6-hexanediol di (meth) acrylate (HDDA), 1,9-nonanediol di (meth) acrylate, diethylene glycol di (meth) acrylate DEGDA), neopentyl glycol di (meth) acrylate (NPGDA), tripropylene glycol di (meth) acrylate (TPGDA), caprolactone-modified hydroxypivalic acid neopentyl glycol ester di (meth) acrylate, propoxylated neopentyl glycol di (meta) ) Acrylate, ethoxy modified bisphenol A di (meth) acrylate, polyethylene glycol 200 di (meth) acrylate, polyethylene glycol 400 di (meth) acrylate, methylene bisacrylamide and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the trifunctional monomer include trimethylolpropane tri (meth) acrylate (TMPTA), pentaerythritol tri (meth) acrylate (PETA), triallyl isocyanate, tris (2-hydroxyethyl) isocyanurate tri (meth) acrylate. Ethoxylated trimethylolpropane tri (meth) acrylate, propoxylated trimethylolpropane tri (meth) acrylate, propoxylated glyceryl tri (meth) acrylate, and the like. These may be used individually by 1 type and may use 2 or more types together.

  Examples of the tetrafunctional or higher functional monomer include pentaerythritol tetra (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, dipentaerythritol hydroxypenta (meth) acrylate, ethoxylated pentaerythritol tetra (meth) acrylate, penta ( And (meth) acrylate ester and dipentaerythritol hexa (meth) acrylate (DPHA). These may be used individually by 1 type and may use 2 or more types together.

  The content of the monofunctional monomer is not particularly limited and may be appropriately selected depending on the purpose. It is preferably 1% by mass or more and 10% by mass or less, and preferably 1% by mass or more with respect to the total amount of the first liquid. 5 mass% or less is more preferable. When the content is 1% by mass or more and 10% by mass or less, there is an advantage that the dispersion stability of the mineral in the first liquid is maintained and the stretchability of the hydrogel structure is improved. The stretchability refers to a property that stretches and does not break when the hydrogel structure is pulled.

  As content of the said polyfunctional monomer, 0.001 mass% or more and 1 mass% or less are preferable with respect to 1st liquid whole quantity, and 0.01 mass% or more and 0.5 mass% or less are more preferable. When the content is 0.001% by mass or more and 1% by mass or less, the elastic modulus and hardness of the obtained hydrogel structure can be adjusted to an appropriate range.

  As content of the said polymerizable monomer, 0.5 mass% or more and 20 mass% or less are preferable with respect to 1st liquid whole quantity. When the content is 0.5% by mass or more and 20% by mass or less, the strength of the hydrogel structure can be made closer to that of a human organ.

--Polymerization initiator--
There is no restriction | limiting in particular as said polymerization initiator, According to the objective, it can select suitably, For example, a photoinitiator, a thermal-polymerization initiator, etc. are mentioned.
As the photopolymerization initiator, any substance that generates radicals upon irradiation with light (particularly, ultraviolet rays having a wavelength of 220 nm to 400 nm) can be used.

  Examples of the photopolymerization initiator include acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p, p′-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, Michler's ketone , Benzyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin-n-propyl ether, benzoin isobutyl ether, benzoin-n-butyl ether, benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2 -Methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) -2-hydroxy-2-methylpropan-1-one, methylbenzoyl Formate, 1-hydroxycyclohexyl phenyl ketone, azobisisobutyronitrile, benzoyl peroxide, di-tert-butyl peroxide and the like can be mentioned. These may be used individually by 1 type and may use 2 or more types together.

  The thermal polymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. For example, an azo initiator, a peroxide initiator, a persulfate initiator, or a redox (oxidation reduction) initiator. Etc. These may be used individually by 1 type and may use 2 or more types together. Among these, a peroxide initiator is preferable.

  The peroxide initiator is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include potassium persulfate, sodium persulfate, ammonium persulfate, sodium peroxodisulfate, and potassium peroxodisulfate. It is done. These may be used individually by 1 type and may use 2 or more types together. Among these, potassium peroxodisulfate is preferable.

<<< Curing Step and Curing Means >>>
The curing step is a step of irradiating predetermined regions of the first liquid, the second liquid layer, and the support forming material layer formed in the curing unit by irradiating with active energy rays.

Examples of the means for curing the layer include an ultraviolet (UV) irradiation lamp and an electron beam. Moreover, it is preferable that a mechanism for removing ozone is provided.
Examples of the ultraviolet (UV) irradiation lamp include a high pressure mercury lamp, an ultrahigh pressure mercury lamp, a metal halide, and an ultraviolet light emitting diode (UV-LED).
The ultra-high pressure mercury lamp is a point light source, but the Deep UV type, which has high light utilization efficiency in combination with an optical system, can irradiate in a short wavelength region.
The metal halide is effective as a colored product because of its wide wavelength region, and metal halides such as Pb, Sn, and Fe are used and can be selected according to the absorption spectrum of the polymerization initiator. There is no restriction | limiting in particular as a lamp | ramp used for hardening, According to the objective, it can select suitably, For example, what is marketed like H lamp, D lamp, or V lamp by Fusion System, etc. Can be used.
There is no restriction | limiting in particular as the light emission wavelength of the said ultraviolet light emitting diode, Although it can select suitably according to the objective, Generally there exists a thing of 365nm, 375nm, 385nm, 395nm, 405nm, In consideration of the influence of color, it is advantageous to emit light at a short wavelength so that the absorption of the polymerization initiator is increased. Among these, an ultraviolet light emitting diode (UV-LED) that generates less heat is used as an ultraviolet (UV) irradiation lamp because it is also used in the three-dimensional structure of the present invention, which is a hydrogel that is easily affected by thermal energy. Is preferred.

  The hydrogel material layer after curing is preferably a hydrogel in which water and a component that dissolves in water are included in a three-dimensional network structure formed by combining a polymer and a mineral. . The hydrogel has improved extensibility, can be peeled off without breaking, and the processing after modeling is greatly simplified.

-Support (core) forming material-
The support forming material is not particularly limited as long as it becomes a support capable of supporting the hydrogel structure of the present invention, but from the viewpoint of removing the support existing in the hollow part after lamination. Those that are soluble in a solvent and those that exhibit a phase transition upon heating or the like and become liquid are preferable. Since the hydrogel structure of the present invention is a hydrogel, soaking the water in the removal of the support-forming material may promote swelling of the shaped article, which is not desirable. For this reason, the thing which shows the solubility to the solvent which does not attack hydrogel is preferable, and what is a solid at 25 degreeC, but a phase change which becomes a liquid at 50 degreeC is preferable. If the support-forming material is a phase-change material, it can be easily removed after the hydrogel structure is formed.
In addition, the support forming material (core forming material) that supports the hollow interior of the hydrogel structure of the present invention and the support forming material that supports the outside of the structure may be the same or different. Moreover, it is not necessary to fill the hollow interior with a support, and it is sufficient that the hollow support has a minimum support shape. In this case, the removal can be performed more efficiently than when the support is filled.

The support-forming material contains a polymerizable monomer, and further contains a polymerization initiator, a colorant and the like, if necessary, and these may be the same as the first liquid.
The phase-change material is, for example, a liquid before curing, and is solidified by irradiating with active energy rays such as ultraviolet rays as in the case of hydrogel, so that it is an environment at room temperature (25 ° C.). Examples include those having the property of being in a solid state below and being liquid in a 60 ° C. environment.

  As one embodiment, a monofunctional ethylenically unsaturated monomer (A) having a straight chain having 14 or more carbon atoms, a polymerization initiator (B), and a solvent (C) capable of dissolving the monomer (A). It is preferable to include.

<Monofunctional ethylenically unsaturated monomer (A) having a straight chain having 14 or more carbon atoms>
The monofunctional ethylenically unsaturated monomer (A) having a straight chain having 14 or more carbon atoms is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include acrylates such as stearyl acrylate and docosyl acrylate. Methacrylates such as stearyl methacrylate and docosyl methacrylate; acrylamides such as palmityl acrylamide and stearyl acrylamide; and vinyls such as vinyl stearate and vinyl docosylate. These may be used individually by 1 type and may use 2 or more types together. Among these, acrylate and acrylamide derivatives are preferable from the viewpoint of photoreactivity, and stearyl acrylate is more preferable from the viewpoint of solubility in a solvent.

  Examples of the polymerization reaction of the monomer (A) include radical polymerization, ionic polymerization, coordination polymerization, and ring-opening polymerization. Among these, radical polymerization is preferable from the viewpoint of controlling the polymerization reaction. Therefore, the monomer (A) having hydrogen bonding ability is preferably an ethylenically unsaturated monomer. Among these, a monofunctional ethylenically unsaturated monomer is preferable from the viewpoint of meltability.

<Polymerization initiator (B)>
There is no restriction | limiting in particular as said polymerization initiator (B), According to the objective, it can select suitably, A thermal polymerization initiator, a photoinitiator, etc. are mentioned. Among these, when modeling a solid thing, a photoinitiator is preferable.

As the photopolymerization initiator, any substance that generates radicals upon irradiation with light (particularly, ultraviolet rays having a wavelength of 220 nm to 400 nm) can be used.
Examples of the photopolymerization initiator include acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p, p′-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, Michler's ketone , Benzyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin-n-propyl ether, benzoin isobutyl ether, benzoin-n-butyl ether, benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2 -Methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) 2-hydroxy-2-methylpropan-1-one, methylbenzoylsulfate Examples include omate, 1-hydroxycyclohexyl phenyl ketone, azobisisobutyronitrile, benzoyl peroxide, and di-tert-butyl peroxide. These may be used individually by 1 type and may use 2 or more types together. Moreover, it is preferable to select a photopolymerization initiator that matches the ultraviolet wavelength of the ultraviolet irradiation device.

<Solvent (C) capable of dissolving monomer (A)>
The solvent (C) is not particularly limited as long as it is a solvent that can dissolve the monomer (A), and can be appropriately selected according to the purpose, thereby preventing a significant decrease in the crystallinity of the polymer side chain. From this point, it is preferable to have a straight chain having 6 or more carbon atoms.
Examples of the solvent (C) having a straight chain having 6 or more carbon atoms include esters such as hexyl acetate and octyl acetate; alcohols such as hexanol, decanol and dodecanol.

  The support-forming material (active energy ray-curable liquid composition) may contain 20% by mass or more and 70% by mass or less of the monofunctional ethylenically unsaturated monomer (A) having a straight chain having 14 or more carbon atoms. Preferably, it is contained in an amount of 30% by mass to 60% by mass. Moreover, it is preferable to contain the said photoinitiator (B) 0.5 to 10 mass%, and it is more preferable to contain 3 to 6 mass%.

In order to obtain a cured product from the liquid support-forming material, for example, it is preferable to cure by irradiating an ultraviolet ray exposure amount of 200 mJ / cm ² or more with an ultraviolet irradiation device. As the ultraviolet irradiation device, the same one that cures the hydrogel structure can be used.

When the monomer (A) contains the polymerization initiator (B) and becomes a polymer upon irradiation with ultraviolet rays, the solvent (C) is held by the polymer. The polymer (A) becomes a solid by arranging the carbon chains in a 25 ° C. environment. When the solvent (C) is held in the polymer (A), there is an effect of suppressing shrinkage and warpage due to crystallization. Further, a solvent (C) having a straight chain having 6 or more carbon atoms is preferred from the viewpoint of curability.
Moreover, it is preferable that the solvent (C) which can melt | dissolve the said monomer (A) is a non-reactive compound which does not react with the said polymerization initiator (B).
In the present invention, the solvent (C) capable of dissolving the monomer (A) refers to a solvent in which the monomer (A) dissolves in the solvent (C) and becomes a uniform liquid.
In the present invention, the non-reactive compound means a compound that does not chemically react even when irradiated with ultraviolet rays.
It is preferable that the solvent (C) is non-reactive because it does not cause a chemical reaction with the photopolymerization initiator and does not inhibit the polymerization reaction of the monomer or the crystallization of the polymer side chain.

-Surface tension-
The surface tension of the support-forming material in the present invention is not particularly limited and may be appropriately selected depending on the intended purpose. For example, at 25 ° C., 20 mN / m or more and 45 mN / m or less is preferable, and 25 mN / m or more. 34 mN / m or less is more preferable. When the surface tension is 20 mN / m or more, the discharge is stable during modeling, the discharge direction is not bent or does not discharge, and when the surface tension is 45 mN / m or less, the discharge nozzle for modeling, etc. When filling the liquid, it can be completely filled. The surface tension can be measured using, for example, a surface tension meter (automatic contact angle meter DM-701, manufactured by Kyowa Interface Science Co., Ltd.).

-Viscosity-
The viscosity of the support-forming material in the present invention is preferably 1,000 mPa · s or less, more preferably 300 mPa · s or less, further preferably 100 mPa · s or less, and more preferably 3 mPa · s or more and 20 mPa · s or less at 25 ° C. Particularly preferred is 6 mPa · s or more and 12 mPa · s or less. When the viscosity exceeds 1,000 mPa · s, there is a case where ejection is not performed even when the temperature of the head is increased. In addition, the said viscosity can be measured in 25 degreeC environment using a rotational viscometer (VISCOMATE VM-150III, the Toki Sangyo Co., Ltd. make) etc., for example.

<<< removal step and removal means >>>
The said removal process is a process of removing the support body containing the said columnar core part.
Examples of the removal of the columnar core part include liquefaction by heat and use of an insoluble solvent for the tubular part. The insoluble means, for example, that when 1 g of the tubular portion is mixed with 100 g of water at 30 ° C. and stirred, 90% by mass or more thereof does not dissolve.

<< Other steps and other means >>
There is no restriction | limiting in particular as said other process, According to the objective, it can select suitably, For example, a layer smoothing process, a peeling process, a discharge stabilization process, the cleaning process of a molded object, the polishing process of a molded object, etc. Is mentioned.

FIG. 4 is a schematic view showing an example of a manufacturing process of a molded body using a three-dimensional modeling apparatus used in the method for manufacturing a hydrogel structure of the present invention.
The three-dimensional modeling apparatus 10 uses a head unit in which inkjet heads (formation material discharging means) that can move in either direction of arrows A and B are arranged on the model support substrate 14 from the head unit 12 to the first. The liquid and the second liquid are laminated while jetting the support forming material from the head unit 11 and curing the first liquid and the second liquid by the adjacent UV irradiation machine 13.
That is, a support forming material (support material) is sprayed from the head unit 12 and solidified to form a first support layer having a reservoir, and the first liquid and the reservoir are formed in the reservoir of the first support layer. The second liquid is ejected from the head unit 11, the first liquid and the second liquid are irradiated with UV light to be cured, and further smoothed using the smoothing member 16. Form a layer.

Next, a second support layer having a reservoir is laminated on the first support layer by injecting and solidifying a support-forming material, and the first support layer is layered with a first support layer. The liquid and the second liquid are ejected, UV light is irradiated, the second modeled object layer is laminated on the first modeled object layer, smoothed, and the modeled body 17 is manufactured.
When using a roller-shaped smooth member, the effect of smoothing is more effectively exhibited when the roller is rotated in the direction of reversing the operation direction.

  Furthermore, in order to keep the gap between the head unit 11, the head unit 12, the UV irradiator 13, the modeled body 17, and the support body 18, the stacking is performed while lowering the stage 15 according to the number of stacking.

  In addition, as the three-dimensional modeling apparatus 10, it is possible to add a forming material collection, recycling mechanism, and the like. You may provide the detection mechanism of the braid | blade which removes the forming material adhering to the nozzle surface, or a non-ejection nozzle. It is also preferable to control the environmental temperature in the apparatus during modeling.

  Using the above-mentioned device, composition distribution and shape control can be performed according to the condition of the individual treatment site of the patient, and a blood vessel model or organ model having a shape and physical property distribution unique to the patient can be formed. Can do.

  For example, using the personal data of the person to be treated (patient), it is possible to provide a blood vessel hardness distribution (composition distribution) as necessary, as well as to have the blood vessel shape of the affected area to be catheterized. In this case as well, it is created based on individual patient data.

  As a method of giving the composition distribution, adjusting the amount of the solvent contained in the hydrogel can be mentioned. This can be realized by using an apparatus having a mechanism for ejecting a plurality of compositions from the respective ink-jet heads by the method using the ink-jet.

A first liquid (hereinafter also referred to as “liquid A”) is used and discharged from the first head. Further, as the second liquid, a solvent capable of diluting the first liquid, mainly a liquid composed of water and a solvent soluble in water (hereinafter also referred to as “liquid B”) is used, and the second head is used. Discharge from. Further, a support forming material used for forming a hollow tube of a blood vessel model is used as the third liquid and discharged from the third head.
The liquid A and the liquid B are printed by a predetermined amount from each ink jet head, and it is possible to precisely control the amount ratio of the liquid dropped on the same location.

Hereinafter, specific embodiment of the manufacturing method of the hydrogel structure of this invention is described.
A method for obtaining hydrogel structures having different hardness, compressive stress and elastic modulus will be described in more detail.
First, three-dimensional shape designed by three-dimensional CAD, or three-dimensional surface data or solid data captured by a three-dimensional scanner or digitizer is converted into an STL format and input to an additive manufacturing apparatus.

  Next, the compression stress distribution of the three-dimensional shape is measured. Although there is no restriction | limiting in particular as a method, For example, by using MR Elastography (henceforth, MRE), the compression stress distribution data of a three-dimensional shape are obtained, and this data is input into an additive manufacturing apparatus. Based on the input compressive stress data, the mixing ratio of liquid A and liquid B to be discharged at a position corresponding to the three-dimensional shape data is determined.

Based on this input data, the modeling direction of the three-dimensional shape to be modeled is determined. The modeling direction is not particularly limited, but usually the direction in which the Z direction (height direction) is the lowest is selected.
When the modeling direction is determined, the projection area of the three-dimensional shape on the XY plane, XZ plane, and YZ plane is obtained. The obtained block shape is cut into slices (slices) in the Z direction with a single layer thickness. The thickness of one layer depends on the material used, but is usually 20 μm or more and 60 μm or less. When there is one model to be modeled, the block shape is arranged so as to be in the middle of the Z stage (a table on which a model that descends one layer at a time for each model) is placed. In addition, when a plurality of models are formed simultaneously, the block shape is arranged on the Z stage, but the block shapes can be stacked. These block shaping, circular cut data (slice data: contour data), and arrangement on the Z stage can be automatically created by specifying the material to be used.

  Next, a modeling process is carried out. FIG. 5 is a schematic view showing an example of a three-dimensional modeling apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 6 is a schematic view showing an example of mixing the first liquid and the second liquid by the droplet discharge method. The different heads α and β (FIG. 5) are moved in both directions, and the liquid A and the liquid B are ejected in a predetermined amount ratio to a predetermined area to form dots. At that time, as shown in FIG. 6, it is possible to mix the A liquid and the B liquid in the dots to obtain a predetermined mixing ratio. Furthermore, by forming continuous dots, a liquid mixture film of liquid A and liquid B having a predetermined mixing ratio in a predetermined region can be produced. And it hardens | cures by irradiating an ultraviolet-ray (UV) light to the liquid mixture film of A liquid and B liquid, and forms the hydrogel film (layer) which has a predetermined mixing ratio in a predetermined area | region like FIG. Can do.

  After forming one layer of the hydrogel film (layer), the stage (FIG. 5) is lowered by a height of one layer. Again, by forming continuous dots on the hydrogel film, a mixed liquid film of liquid A and liquid B having a predetermined mixing ratio in a predetermined region is produced. The mixed liquid film of A liquid and B liquid is cured by irradiating with ultraviolet (UV) light to form a hydrogel film. By repeating these laminations, three-dimensional modeling becomes possible.

  The hydrogel structure three-dimensionally formed in this way has different mixing ratios of the liquid A and the liquid B in the three-dimensional hydrogel of FIG. 5 and can continuously change the elastic modulus. By adjusting the blending ratio pattern for each fault, it is possible to obtain a hydrogel structure partially having arbitrary physical characteristics.

  In addition, by placing an ultraviolet (UV) light irradiator adjacent to the inkjet head that ejects the first liquid and the second liquid, the time required for the smoothing process can be saved, and high-speed modeling is possible.

  The hydrogel structure used in the present invention can vary the hardness arbitrarily by combining the first liquid and the second liquid (diluent) and changing the composition ratio while using the same material. Can do. For this reason, it is possible to easily provide the hardness distribution of the blood vessels along the personal data by using a plurality of ink jet heads and changing the ratio between them when modeling by the ink jet method.

  The hydrogel has a structure containing a large amount of water, is very close to the composition of the human body, and has a very close texture. Combining this with 3D printing is very useful when creating a blood vessel model.

Since the hydrogel structure, blood vessel model, and organ model of the present invention can be produced by 3D printing technology, it is possible to form a model that reproduces this shape and physical properties based on the affected area data of the patient. . For this reason, it can be usefully used for simulation before difficult surgery.
For example, in a conventional operation (stent insertion into an aneurysm), the shape of the aneurysm is read from an X-ray image, and a stent that seems to have an appropriate shape is selected during the operation and used. However, this is performed based on the experience of a doctor (surgeon), and there are many cases in which it takes time to make a decision or an optimum one cannot be selected.
The problem of what kind of member (stent, etc.) should be selected according to the shape and physical properties of the aneurysm may increase the success rate of surgery by considering it before surgery. I can expect.

Examples of the present invention will be described below, but the present invention is not limited to these examples.
The water content, elastic modulus, 10-point average value of maximum inner diameter, and transmittance were measured as follows.

(Moisture content)
The moisture content was measured using a heat-drying moisture meter (device name: MS-70, manufactured by A & D Corporation).

(Elastic modulus)
For the elastic modulus, a universal testing machine (device name: AG-I, manufactured by Shimadzu Corporation), a compression jig for a load cell 1 kN, 1 kN, and a sample modeled in a shape of 30 mm × 30 mm × 8 mm were installed. The stress against compression applied to the load cell was recorded in a computer, and the stress against displacement was plotted. In addition, an elastic modulus shows the inclination of the compressive stress at the time of 20% compression.

(10 points average value of maximum inner diameter)
Using an inverted metal microscope (device name: GX51, manufactured by Olympus Co., Ltd.), the maximum inner diameter of the adjacent portion where the outer diameter of the structure is the same was measured at 10 points, the average value was obtained, and the 10-point average value was obtained. . In addition, in the adjacent part where the outer diameter of the said hydrogel structure is the same, when ten said maximum inner diameters cannot be measured, it was set as the average value of the point which can be measured. The outer diameter was measured using an inverted metal microscope (device name: GX51, manufactured by Olympus Corporation).

(Transmittance)
The structure is cut in the longitudinal direction at the hollow tube portion to form a flat plate, and the transmittance in the wavelength range of 400 nm to 700 nm is measured with a commercially available spectrophotometer (device name: UV-3100, manufactured by Shimadzu Corporation, integration) Unit use).

(Preparation example 1 of hydrogel-forming material)
<Preparation of the first liquid A1>
While stirring 51.0 parts by mass of ion-exchanged water (hereinafter also referred to as “pure water”) subjected to vacuum degassing for 30 minutes, [Mg _5.34 Li _0.66 Si ₈ O as a layered clay mineral] Synthetic hectorite (Laponite XLG, manufactured by Rockwood) having a composition of ₂₀ (OH) 4] Na ^- _0.66 was added little by little and stirred. Further, 0.3 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added and stirred at 40 ° C. for 2 hours to prepare a dispersion.
16.8 parts by mass of acryloylmorpholine (manufactured by KJ Chemicals Co., Ltd.) and methylenebisacrylamide (manufactured by Tokyo Kasei Kogyo Co., Ltd.) were passed through an activated alumina column as a polymerizable monomer to remove the polymerization inhibitor. ) 0.2 parts by mass and 3.0 parts by mass of N, N′-dimethylacrylamide (manufactured by KJ Chemicals) were added.
Furthermore, 22.0 masses of glycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.) and 0.3 parts by mass of Emulgen LS106 (manufactured by Kao Corporation) were added. Next, after shading the container, 0.5 parts by mass of Irgacure 1173 (BYK) and 0.4 parts by mass of N, N, N ′, N′-tetramethylethylenediamine (Tokyo Chemical Industry Co., Ltd.) are added. The mixture was stirred for 30 minutes. Next, vacuum degassing was performed for 10 minutes, and then filtration was performed using a syringe filter (manufactured by ADVANTEC) having an average pore diameter of 0.8 μm to obtain a homogeneous first liquid A1.

(Dilution Material Preparation Example 1)
<Preparation of second liquid B1>
A second liquid B1 was prepared in the same manner as in Preparation Example 1 of the hydrogel-forming material except that the composition was changed to the composition shown in Table 1 below in Preparation Example 1 of the hydrogel-forming material.

In Table 1, the trade names of the components and the names of the manufacturing companies are as follows.
-Acryloylmorpholine: manufactured by KJ Chemicals Co., Ltd.-Methylenebisacrylamide: manufactured by Tokyo Chemical Industry Co., Ltd.-N, N'-dimethylacrylamide: Monofunctional monomer manufactured by KJ Chemicals Co., Ltd.-Synthetic hectorite: manufactured by RockWood, Inc., trade name: LAPONITE XLG
-Glycerin: Sakamoto Pharmaceutical Co., Ltd.-Etidronic acid: Tokyo Chemical Industry Co., Ltd.-N, N, N ', N'-tetramethylethylenediamine: Tokyo Chemical Industry Co., Ltd.-Emulgen LS106: Kao Corporation-Irgacure 1173 : BYK company

(Preparation Example 1 of Support (Core) Forming Material)
<Preparation of Support Forming Material 1>
1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd.) 55.0 parts by mass, stearyl acrylate (manufactured by Tokyo Chemical Industry Co., Ltd.) 42.0 parts by mass, and Irgacure 819 (manufactured by BASF) 3.0 mass% at 40 ° C. The temperature was adjusted, stirred for 30 minutes, mixed and dissolved to prepare Support Forming Material 1. The composition is shown in Table 2 below.

In Table 2, the trade names of the components and the names of the manufacturing companies are as follows.
Stearyl acrylate: manufactured by Tokyo Chemical Industry Co., Ltd. 1-Dodecanol: manufactured by Tokyo Chemical Industry Co., Ltd. Irgacure 819: manufactured by BASF Corporation

(Reference Examples 1-2)
The first liquid A1 and the second liquid B1 are mixed at a volume ratio shown in Table 3 below, and poured into a 30 mm × 30 mm × 8 mm mold, and an ultraviolet irradiator (device name: SPOT CURE SP5-250DB, USHIO INC.) After being cured using a company-made), the mixture was allowed to stand at 27 ° C. for 12 hours to obtain hydrogel samples for compression tests of Reference Examples 1 and 2. The water content and elastic modulus of the obtained hydrogel sample were measured. The results are shown in Table 3 below.

(Examples 1-2)
Using the modeling apparatus shown in FIG. 4, the first liquid A1 and the second liquid B1 and the support-forming material 1 (both active energy ray-curable compositions) are discharged at the volume ratio shown in Table 4 below. Then, curing was repeated with ultraviolet rays to prepare a layered product. Next, the layered object is left in a constant temperature bath at 50 ° C. for 30 minutes, and the support (columnar core), which is a cured product of the support-forming material 1, is liquefied to remove it. By washing away the remaining support (columnar core) with hot water at 0 ° C., a hydrogel structure having a hollow tube shape as shown in FIG. 1 was obtained. All of the obtained hydrogel structures had a harder composition on the blood vessel wall than on other surrounding hydrogels. As a result of inserting a catheter into this and confirming the texture, the texture was very close to that of an actual blood vessel. The water content and elastic modulus are the same as in Reference Example 1.

(Comparative Examples 1-2)
In Example 1, a hydrogel structure was obtained in the same manner as in Example 1 except that the volume ratio was changed as shown in Table 4 below. When the texture was confirmed by inserting a catheter into the obtained hydrogel structure, the texture was different from the actual one. The elastic modulus was measured in the same manner as in Reference Example 1. As a result, Comparative Example 1 was 0.21 MPa as the blood vessel wall, 0.21 MPa as the other hydrogel, Comparative Example 2 was 0.02 MPa as the blood vessel wall, and 0.02 MPa as the other hydrogel.

(Comparative Example 3)
A shaped article was obtained in the same manner as in Example 1 except that the support (columnar core) was composed of SUP706 (Stratasys) and the blood vessel wall and main body were composed of TangoBlack (Stratasis). . The obtained model was immersed in water for 12 hours, and the support-forming material was removed to obtain a structure.
When the texture was confirmed by inserting a catheter into the obtained structure, the blood vessel was very hard, caught, and far from the real thing. The elastic modulus was measured in the same manner as in Reference Example 1. The result was 2.0 MPa for both the vascular wall and other hydrogels.

  Next, “texture” was evaluated as follows. The results are shown in Table 4 below.

(Texture)
The obtained hydrogel structure was subjected to catheter insertion evaluation by a doctor, and the texture of the insertion of the catheter (trade name: Echelon 10, manufactured by COVIDEN) was evaluated based on the following evaluation criteria.
-Evaluation criteria-
○: The texture is very close to that of an actual blood vessel, and is a level that can be preferably used for catheter insertion practice. Δ: The texture is different from that of an actual blood vessel, but is a level that can be used for practice of catheter insertion. Is a distant texture that cannot be used for catheter insertion practice

(Example 3)
The hydrogel structure obtained in the same manner as in Example 1 was incorporated in a glass container. The feel of the catheter during insertion has not changed, and handling has been improved.

Example 4
The hydrogel structure obtained in the same manner as in Example 1 was built in a container made of polycarbonate resin. The feel of the catheter during insertion has not changed, and handling has been improved.

  Next, “preservability” was evaluated as follows.

(Storability)
Using the hydrogel structures produced in Example 1, Example 3, and Example 4, the product was stored for 3 days under atmospheric conditions (25 ° C., 55% RH).
As a result, the surface of the hydrogel structure of Example 1 was slightly dried and the hardness increased, but no change was observed in the structures of Examples 3 and 4.

(Preparation example 2 of hydrogel-forming material)
<Preparation of the first liquid A2>
Hereinafter, deionized water that has been degassed for 30 minutes is referred to as pure water.
First, synthetic hectorite having a composition of [Mg _5.34 Li _0.66 Si ₈ O ₂₀ (OH) ₄ ] Na ⁻ _0.66 as a layered clay mineral while stirring 60.0 parts by mass of pure water (product) Name: Laponite XLG, manufactured by Rockwood) was added little by little to a total of 6.0 parts by mass, and stirred to prepare a dispersion. Next, 0.3 parts by mass of etidronic acid was added as a dispersant for synthetic hectorite.
Next, 22.0 parts by mass of acryloylmorpholine (manufactured by KJ Chemicals Co., Ltd.) obtained by passing an activated alumina column through the activated alumina column and removing the polymerization inhibitor as a polymerizable monomer, and methylenebisacrylamide (organic crosslinking agent) were obtained. 0.22 parts by mass, manufactured by Tokyo Chemical Industry Co., Ltd., 10.2 parts by mass of glycerin as a drying inhibitor, and 0.3 parts by mass of Emulgen LS106 (manufactured by Kao Corporation) were added and mixed.
Next, after adding 0.4 parts by mass of N, N, N ′, N′-tetramethylethylenediamine as a polymerization accelerator, 0.6 parts by mass of Irgacure 184 (manufactured by BASF) is added and stirred and mixed. did.
After stirring and mixing, vacuum degassing was performed for 10 minutes. Subsequently, by performing filtration, impurities and the like were removed to obtain a homogeneous first liquid A2. The composition is shown in Table 5 below.

(Dilution Material Preparation Example 2)
<Preparation of second liquid B2>
A second liquid B2 was obtained in the same manner as in Preparation Example 2 of the hydrogel-forming material, except that the composition was changed to the composition shown in Table 5 below in Preparation Example 2 of the hydrogel-forming material.

In Table 5, the trade names of the components and the names of the manufacturing companies are as follows.
・ Acryloyl morpholine: manufactured by KJ Chemicals Co., Ltd. ・ methylene bisacrylamide: manufactured by Tokyo Chemical Industry Co., Ltd. ・ Synthetic hectorite: manufactured by RockWood Co., Ltd., trade name: LAPONITE XLG
-Glycerin: Sakamoto Pharmaceutical Co., Ltd.-Etidronic acid: Tokyo Chemical Industry Co., Ltd.-N, N, N ', N'-tetramethylethylenediamine: Tokyo Chemical Industry Co., Ltd.-Emulgen LS106: Kao Corporation-Irgacure 184 : BASF made

(Reference Examples 3-5)
As a hydrogel-forming material, the first liquid A2 and the second liquid B2 are mixed at a volume ratio shown in Table 6 below and poured into a 30 mm × 30 mm × 8 mm mold, and an ultraviolet irradiator (device name: SPOT CURE SP5). -250DB, manufactured by Ushio Electric Co., Ltd.), and then allowed to stand at 27 ° C. for 12 hours to obtain hydrogel samples for compression tests of Reference Examples 3 to 5. The water content and elastic modulus of the obtained hydrogel sample were measured. The results are shown in Table 6 below.

  From the results of Table 6, it was found that Reference Examples 3 to 5 can set a predetermined strength (compression stress, elastic modulus) and moisture content by adjusting the volume ratio of the first liquid and the second liquid. .

(Preparation Example 2 of Support (Core) Forming Material)
<Preparation of Support Forming Material 2>
10.0 Dodecanol (Tokyo Chemical Industry Co., Ltd.) 50.0 parts by mass, acryloylmorpholine (KJ Chemicals Co., Ltd.) 46.0 parts by mass, and Irgacure 819 (BASF Co., Ltd.) 4.0 parts by mass are mixed and dissolved. Thus, a support forming material 2 was prepared. The composition is shown in Table 7 below.

(Example 5)
Using the modeling apparatus shown in FIG. 4, the first liquid A2 and the second liquid B2 and the support forming material 2 (both active energy ray-curable compositions) are discharged at the volume ratio shown in Table 8 below. Then, curing was repeated with ultraviolet rays to prepare a layered product. Next, the layered product is allowed to stand in a 50 ° C. constant temperature bath for 30 minutes to remove the support (columnar core), which is a cured product of the support-forming material 2, by liquefying, and further, 50 The hydrogel structure having a hollow tube shape as shown in FIG. 2 was obtained by washing away the support (columnar core) remaining in the hot water at 0 ° C. In the same manner as in Example 1, the elastic modulus, the maximum inner diameter of the thinnest portion, and the transmittance were measured. The results are shown in Tables 8 and 9 below.

(Example 6)
In Example 5, except having changed into the volume ratio shown in following Table 8, it carried out similarly to Example 5, and obtained the structure which has a knob part as shown in FIG. In the same manner as in Example 1, the elastic modulus, the maximum inner diameter of the thinnest portion, and the transmittance were measured. The results are shown in Tables 8 and 9 below.

(Comparative Examples 4-5)
In Example 5, the hydrogel structure was obtained like Example 5 except having changed into each volume ratio shown in Table 8 below. In the same manner as in Example 1, the elastic modulus, the maximum inner diameter of the thinnest portion, and the transmittance were measured. The results are shown in Tables 8 and 9 below.

(Comparative Example 6)
Except that the support (columnar core) was made of SUP706 (Stratasys) and the other hydrogel, blood vessel wall, and aneurysm were made of TangoBlack (Stratasis), the same as Example 5. I got a model. The obtained model was immersed in water for 12 hours, and the support-forming material was removed to obtain a structure. The elastic modulus was measured in the same manner as in Reference Example 1. The result was 2.0 MPa, respectively.

  Next, “texture” was evaluated as follows. The results are shown in Table 9 below.

(Texture)
The obtained hydrogel structure was subjected to catheter insertion evaluation by a doctor, and the texture of the insertion of the catheter (trade name: Echelon 10, manufactured by COVIDEN) was evaluated based on the following evaluation criteria.
-Evaluation criteria-
○: The texture is very close to the actual blood vessel ×: The texture is far from the actual blood vessel

In Example 5, the texture of the aneurysm was able to reproduce the texture close to that of the actual aneurysm, and the texture very close to that of the actual blood vessel could be reproduced.
In Example 6, the blood vessel wall portion had the same degree of hardness as the surrounding portion, but the texture of the same hardness as that of the mouse having a low blood vessel wall hardness could be reproduced.
In Comparative Examples 4 to 6, the blood vessels were very hard, caught, and had a texture far from the real thing.

  From the above results, as in the example, the blood vessel model constituted by the hydrogel structure and partially adjusted in hardness and moisture content is pre-operative simulation and blood vessel catheter insertion in which the texture is very close to the real thing. It became clear that it was suitable for practice.

As an aspect of this invention, it is as follows, for example.
<1> including water and polymer,
Has a hollow tube shape,
It is a hydrogel structure characterized by satisfying at least one of the following (1) to (2).
(1) At least a part of the hollow tube shape is in contact with a hydrogel having an elastic modulus different from that of the hydrogel constituting the hollow tube. (2) At least two types of the hollow tube shape having different elastic moduli. <2> The water content of the hydrogel structure having the hollow tube shape formed by the hydrogel is lower than the water content of the hydrogel having an elastic modulus different from that of the hydrogel structure. It is a hydrogel structure as described in above.
<3> When the elastic modulus of one part in the hollow tube shape is X (MPa) and the elastic modulus of another part adjacent to the one part is Y (MPa), the absolute value of the elastic modulus change The hydrogel structure according to any one of <1> to <2>, wherein (| X−Y |) is 0.1 MPa or more.
<4> The elastic modulus of the hydrogel structure having the hollow tube shape is 0.1 MPa or more and 0.5 MPa or less,
The hydrogel structure according to any one of <1> to <3>, wherein an elastic modulus in a hydrogel having an elastic modulus different from that of the hydrogel structure is 0.005 MPa to 0.1 MPa.
<5> The hydrogel structure according to any one of <1> to <4>, wherein transmittance in a visible light region is 80% or more.
<6> The hydrogel structure according to any one of <1> to <5>, wherein a 10-point average value of maximum inner diameters in at least a part of the hydrogel structure is 1.0 mm or less.
<7> Further containing minerals,
The hydrogel structure according to any one of <1> to <6>, including a hydrogel in which the water is included in a three-dimensional network structure formed by combining the polymer and the mineral. is there.
<8> The hydrogel structure according to any one of <1> to <7>, further including a water-soluble organic solvent.
<9> A blood vessel model comprising the hydrogel structure according to any one of <1> to <8>.
<10> An organ model comprising the hydrogel structure according to any one of <1> to <8>, wherein the outer shape is a shape imitating an organ shape.
<11> At least one of the blood vessel model according to <9> and the organ model according to <10>,
A technique practice tool comprising: a catheter and / or an endoscope.
<12> A method for producing a hydrogel structure having a hollow tube shape,
A columnar core portion is formed using a core portion forming material, and the tubular core portion is covered with a second hydrogel having an elastic modulus different from that of the first hydrogel and the first hydrogel. After the formation, the columnar core part is removed.
<13> The method for producing a hydrogel structure according to <12>, wherein a hydrogel structure satisfying at least one of the following (1) to (2) is produced.
(1) At least a part of the hollow tube shape is in contact with a hydrogel having an elastic modulus different from that of the hydrogel constituting the hollow tube. (2) At least two types of the hollow tube shape having different elastic moduli. <14> The method for producing a hydrogel structure according to any one of <12> to <13>, wherein the <14> columnar core portion and the tubular portion are formed by a layered manufacturing method. .
<15> The method for producing a hydrogel structure according to any one of <12> to <14>, wherein the core forming material and the first liquid are both active energy ray-curable compositions.
<16> The method for producing a hydrogel structure according to any one of <12> to <15>, wherein the columnar core is removed by liquefaction by heat.
<17> The method for producing a hydrogel structure according to any one of <12> to <15>, wherein a solvent insoluble in the tubular portion is used when removing the columnar core portion.
<18> The method for producing a hydrogel structure according to any one of <15> to <17>, wherein the first liquid further contains a mineral.
<19> The method for producing a hydrogel structure according to any one of <15> to <18>, wherein the first liquid further contains an organic solvent.
<20> The method for producing a hydrogel structure according to <19>, wherein the organic solvent is a water-soluble organic solvent.

  The hydrogel structure according to any one of <1> to <8>, the blood vessel model according to <9>, the organ model according to <10>, the technique training tool according to <11>, And according to the method for producing a hydrogel structure according to any one of <12> to <20>, the conventional problems can be solved and the object of the present invention can be achieved.

DESCRIPTION OF SYMBOLS 10 Three-dimensional modeling apparatus 11, 12 Head unit 13 UV irradiation machine 14 Modeling object support substrate 15 Stage 16 Smoothing member 17 Modeling body 18 Support body (support material)

Japanese Patent Laying-Open No. 2015-69054 Japanese Patent Laying-Open No. 2015-219371 JP 2012-189909 A JP 2009-273508 A Japanese Patent No. 361568

Claims (16)

Including water and polymer,
Has a hollow tube shape,
A hydrogel structure characterized by satisfying at least one of the following (1) to (2).
(1) At least a part of the hollow tube shape is in contact with a hydrogel having an elastic modulus different from that of the hydrogel constituting the hollow tube. (2) At least two types of the hollow tube shape having different elastic moduli. Formed by hydrogel   The hydrogel structure according to claim 1, wherein the water content of the hydrogel structure having the hollow tube shape is lower than the water content of a hydrogel having an elastic modulus different from that of the hydrogel structure.   When the elastic modulus of one part in the hollow tube shape is X (MPa) and the elastic modulus of another part adjacent to the one part is Y (MPa), the absolute value (| X The hydrogel structure according to any one of claims 1 to 2, wherein -Y |) is 0.1 MPa or more. The elastic modulus in the hydrogel structure having the hollow tube shape is 0.1 MPa or more and 0.5 MPa or less,
The hydrogel structure according to any one of claims 1 to 3, wherein an elastic modulus of the hydrogel having an elastic modulus different from that of the hydrogel structure is 0.005 MPa or more and 0.1 MPa or less.   The hydrogel structure according to any one of claims 1 to 4, wherein the transmittance in the visible light region is 80% or more.   The hydrogel structure according to any one of claims 1 to 5, wherein an average value of 10 points of the maximum inner diameter in at least a part of the hydrogel structure is 1.0 mm or less. Further containing minerals,
The hydrogel structure according to any one of claims 1 to 6, comprising a hydrogel in which the water is included in a three-dimensional network structure formed by combining the polymer and the mineral.   The hydrogel structure according to any one of claims 1 to 7, further comprising a water-soluble organic solvent.   A blood vessel model comprising the hydrogel structure according to any one of claims 1 to 8.   An organ model comprising the hydrogel structure according to any one of claims 1 to 9, wherein the outer shape is a shape imitating an organ shape. At least one of the blood vessel model according to claim 9 and the organ model according to claim 10;
A technique practice tool comprising at least one of a catheter and an endoscope. A method for producing a hydrogel structure having a hollow tube shape,
A columnar core portion is formed using a core portion forming material, and the tubular core portion is covered with a second hydrogel having an elastic modulus different from that of the first hydrogel and the first hydrogel. After forming, the columnar core part is removed, and the manufacturing method of the hydrogel structure characterized by the above-mentioned.   The method for producing a hydrogel structure according to claim 12, wherein the columnar core part and the tubular part are formed by a layered manufacturing method.   The method for producing a hydrogel structure according to any one of claims 12 to 13, wherein the core portion forming material and the first liquid are both active energy ray-curable compositions.   The method for producing a hydrogel structure according to claim 12, wherein the columnar core is removed by liquefaction by heat.   The method for producing a hydrogel structure according to any one of claims 12 to 14, wherein a solvent insoluble in the tubular portion is used when removing the columnar core portion.