JP2022030867A - Molding method - Google Patents

Abstract

To provide a method for modeling three-dimensional objects in which the biophysical properties obtained by measuring living organisms are reproduced with high accuracy.SOLUTION: A molding method having a molding process of molding a three-dimensional object using a 3D printer based on medical 3D data of a living body, the medical 3D data is created based on medical image data obtained by photographing the living body with a medical imaging device and biophysical properties obtained by measuring the living body with MRE, and the three-dimensional object has a distribution of intensity properties corresponding to the distribution of the biophysical properties.SELECTED DRAWING: Figure 5

Description

The present invention relates to a modeling method.

The progress of three-dimensional three-dimensional modeling technology is remarkable, and various 3D printers such as Fused Deposition Modeling, Binder Jetting, Stereolithography, Powder Deposition Modeling, and Material Jetting are used in the manufacturing industry. Further, as materials used in 3D printers, various materials have been developed in addition to the conventionally known metals and resins. New applications corresponding to these various materials have been proposed, and are expected to be applied not only to the industrial field but also to the medical field and the healthcare field. Examples of applications of 3D printers in the medical field include, for example, the formation of implantable artificial bones using titanium, hydroxyapatite, PEEK, etc., and the application to research on artificial organs by direct stacking of cells. Examples of applications of 3D printers in the field of healthcare include applications to hearing aids and artificial limbs that need to reflect a shape peculiar to an individual.

As another application example of the 3D printer in the medical field, it is expected to be applied to a model that imitates an actual organ shape or a living body for the purpose of surgical training and simulation. As a background that is expected to be applied to such models, the development of medical equipment has progressed in recent years, and it is a minimally invasive type that reduces the burden on patients by catheters, endoscopes, robot assists, etc. One point is that medical care is becoming mainstream. This is because surgical operations using these medical devices require extremely advanced techniques and skills, and the importance of surgical training using appropriate models is recognized from the viewpoint of preventing medical accidents. Further, in difficult surgery with few cases, if a model that reproduces the details of the target site in advance can be obtained, it becomes possible to perform a detailed preoperative simulation.

As a model imitating a conventionally known organ or the like, there is a model produced by a 3D printer and composed of a hard material such as an acrylic resin and a urethane resin. However, hard materials are hard as materials, and it is difficult to reproduce the texture in an actual organ.
Further, as another model that imitates a conventionally known organ or the like, an aqueous gel such as a silicone elastomer and polyvinyl alcohol, which is produced by a casting method using a template and disclosed in Patent Document 1, is used. Examples include the configured model. When it is produced by the casting method, it can be produced by using a material having a wide selection of materials and having a texture close to that of an actual organ such as polyvinyl alcohol. However, since the casting method is a method of integrally forming with a single material, it is difficult to reproduce the physical characteristic distribution in the organ that occurs based on the site of the organ to be produced, the diseased area, or the like.
Furthermore, since it is difficult to directly contact and measure the texture of an actual organ, it is generally necessary to adjust the texture to a texture close to that of the actual organ based on the results of hearings from doctors. .. However, since the texture information differs depending on the patient to be interviewed, it is difficult to create a model that reproduces the texture in the organ of a specific patient.

An object of the present invention is to provide a method for modeling a three-dimensional model in which the physical characteristics of a living body obtained by measuring a living body are accurately reproduced.

The present invention is a modeling method including a modeling process of modeling a three-dimensional model using a 3D printer based on medical 3D data of a living body, and the medical 3D data is obtained by photographing the living body with a medical imaging device. The three-dimensional model is created based on the medical image data acquired by the above and the biological physical characteristics acquired by measuring the living body by MRE, and the three-dimensional model has a distribution of strength physical properties corresponding to the distribution of the biological physical properties. It relates to a modeling method characterized by that.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a modeling method capable of modeling a three-dimensional model in which the biological characteristics obtained by measuring a living body are accurately reproduced.

FIG. 1 is a schematic diagram showing an example of a medical image data set. FIG. 2 is a schematic diagram showing an example of medical 3D data. FIG. 3 is a schematic diagram showing an example of medical 3D data. FIG. 4 is a schematic diagram showing an example of region-specific medical 3D data acquired by dividing the medical 3D data into voxel regions. FIG. 5 is a schematic diagram showing an example of STL format data acquired by converting the area-specific medical 3D data into a surface model. FIG. 6 is a schematic diagram showing an example of FAV format data acquired by converting medical 3D data for each area into FAV format. FIG. 7 is a schematic diagram showing an example of the strength physical properties of 7 gradations represented by the arrangement pattern of the high-strength modeling composition and the low-strength modeling composition. FIG. 8 is a schematic diagram showing an example of a state in which a water-swellable layered clay mineral as a mineral and a water-swellable layered clay mineral are dispersed in water. FIG. 9 is a schematic view showing an example of a modeling device for a hydrogel three-dimensional model. FIG. 10 is a schematic view showing an example in which a hydrogel three-dimensional object is peeled off from a support.

1. 1. Modeling Method The modeling method of the present invention includes a modeling step of modeling a three-dimensional model (also referred to as a "model") using a 3D printer based on medical 3D data of a living body. Further, in the modeling method of the present invention, as necessary, as a step executed before the above-mentioned modeling step, an acquisition step of acquiring medical 3D data of a living body and a modeling 3D data are generated based on the medical 3D data. It may have a production step to be carried out. Further, the modeling method of the present invention may include an evaluation step for evaluating the accuracy of the modeled three-dimensional model as a step executed after the above modeling process, if necessary.
In the present disclosure, the term "living body" refers to a human or at least a part constituting a non-human living body, and the number of objects may be one or more. In addition, at least a part constituting a human or a non-human organism represents, for example, a predetermined region in a living body such as a chest, a predetermined organ in the living body, and the like.
Further, in the present disclosure, "to model a three-dimensional model using a 3D printer based on the medical 3D data of a living body" means to directly input the medical 3D data into the 3D printer to model the three-dimensional model. Not limited to the case of using medical 3D data, there is also a case of indirectly using medical 3D data such as inputting 3D data for modeling generated based on 3D medical data into a 3D printer to form a three-dimensional model. show.

(1) Acquisition Step The modeling method of the present invention preferably includes an acquisition step for acquiring medical 3D data of a living body. In the present disclosure, the "medical 3D data" is created based on at least the medical image data acquired by photographing the living body with a medical imaging device and the biological characteristics acquired by measuring the living body by MRE. Represents the data. That is, the acquisition step of acquiring the medical 3D data of the living body includes an imaging step of acquiring the medical image data by photographing the living body with a medical imaging device and a measuring step of acquiring the biological physical characteristics by measuring the living body by MRE. It has a creation step of creating medical 3D data based on medical image data and biological characteristics.

(I) Imaging step The imaging step is a step of acquiring medical image data by photographing a living body with a medical imaging device. The medical imaging device, also called modality, is a device that scans a living body as a subject and acquires medical image data. Examples of the medical imaging device include a CT (Computed Tomography) device, an MRI (Magnetic Resonance Imaging) device, an ultrasonic diagnostic device, and the like. Among these, it is preferable to use an MRI apparatus from the viewpoint of being able to perform MRE measurement in the measurement step described later. The medical imaging device performs slice tomography in which a cross section of a living body is photographed multiple times. As a result, as shown in FIG. 1, a plurality of medical image data which are images showing a cross section of a living body can be acquired. Each of the plurality of medical image data (also referred to as a "medical image data set") is preferably an image in DICOM format, which is an international standard for medical image exchange. Further, the medical image data includes image density information indicating the image density acquired by the medical imaging apparatus. The image density is, for example, a CT value (X-ray transmittance) when a CT device is used as a medical imaging device, an MRI signal value when an MRI device is used, and an ultrasonic diagnostic device. Is the reflection intensity.

(II) Measurement step The measurement step is a step of acquiring biological characteristics by measuring the living body by MRE. The MRE measurement means the measurement by the method of magnetic resonance elastography (MRE). This method is a non-invasive method for measuring the viscoelastic distribution inside a subject by taking an image with an MRI device while generating a shear wave inside the subject using a vibration exciter. That is, it is preferable that the biological characteristics obtained by measuring the living body by MRE are viscoelastic. As a method of acquiring the viscoelasticity of a living body, a method of measuring by ultrasonic elastography can be mentioned in addition to a method of performing MRE measurement. In this respect, while the information obtained by ultrasonic elastography is one-dimensional, the information obtained by MRE measurement is two-dimensional and it is easy to generate 3D data, so MRE measurement can be performed. preferable. If the object to be measured is an organ such as the heart or blood vessel that is accompanied by periodic movements, the amount of deformation of the organs due to this movement is measured, and the biological properties are estimated from the measured values based on a mechanical model or the like. There is also a way to do it. However, the biological characteristics obtained by this method are only estimated values, and are inferior to the MRE measurement from the viewpoint of accurate information acquisition of the living body. In addition, this method can be used only when the measurement target is an organ with periodic movement such as the heart or blood vessel, so that the organ without periodic movement or periodic movement can be used. It is preferable to perform MRE measurement because it is possible to measure an organ for which it is difficult to measure the amount of deformation due to the above. Further, the MRE measurement is often included in the system as an optional function of the MRI apparatus, and it is also preferable that the imaging process and the measurement step can be executed by the same MRI apparatus. Along with this, the imaging step by the MRI apparatus and the measurement step by the MRI apparatus can be performed almost at the same time. It is preferable that it can be performed almost at the same time, that the burden on the subject such as a patient can be reduced, and that the acquisition of medical image data and the acquisition of biological characteristics can be performed almost at the same time, and accurate biological information can be obtained. In particular, the latter point is an important point of view, considering that the object of photography and measurement is a living body having a property of easily changing in shape, physical properties, etc. over time. In addition, almost simultaneous means a case where at least a part of the time of the photographing process and the time of the measuring process overlap, and the case where both the photographing process and the measuring process can be executed by using the MRI apparatus once. In addition, since MRE measurement can be performed on a living body, it is also preferable in that it is possible to obtain biological characteristics in an organ in which blood pressure is applied in the living body.

(III) Creation step The creation step is a step of creating medical 3D data based on the medical image data acquired in the imaging process and the biological characteristics acquired in the measurement step. The medical 3D data includes a plurality of voxels created based on the medical image data, image density information indicating the image density in the medical image data assigned to each voxel, and biological properties indicating the biological properties assigned to each voxel. Information and information including. In other words, the medical 3D data is information associated with voxels, image density information, and biological characteristic information.

The method of creating medical 3D data will be specifically described.
First, from the medical image data acquired in the imaging process, medical 3D data corresponding to 3D image processing by a medical imaging device or an image processing device related to the medical imaging device (also referred to as "medical image capturing device"). Is created. The medical 3D data is a collection of voxels containing at least one minimum unit such as a cube as shown in FIG. 2, and various information can be associated with each voxel. Next, the medical imaging apparatus or the like associates image density information indicating the image density in the medical image data acquired in the imaging step with each voxel. Further, a medical imaging device or the like associates the biological property information indicating the biological property acquired in the measurement step with each voxel. As a result, as shown in FIG. 3, it is possible to create medical 3D data which is information associated with voxels, image density information, and biological characteristic information. For medical 3D data, voxel region segmentation can be performed using image density information. Voxel region division means classifying and segmenting voxels having similar image densities. This enables shape recognition, structural division, tissue analysis, 3D image analysis, and the like of the internal structure of the living body based on the medical 3D data. For example, from the medical 3D data of the living body to the medical 3D of a predetermined tissue such as the liver. You can get the data. In the present invention, as shown in FIG. 4, the medical 3D data in the partial region acquired by dividing the medical 3D data into voxel regions is referred to as region-specific medical 3D data. It should be noted that the area-specific medical 3D data is a concept included in the medical 3D data.

(2) Generation Step The modeling method of the present invention preferably has a generation step of generating modeling 3D data based on medical 3D data. In the present disclosure, the "modeling 3D data" is data generated based on medical 3D data and represents data input to a 3D printer. The modeling 3D data may be composed of one data or a plurality of data. Hereinafter, two specific examples of a method for generating 3D data for modeling will be described, but the method is not limited to these.

(I) Generation of 3D data for modeling including data in STL format A case of generating 3D data for modeling including data in STL (Standard Triangled Language) format based on medical 3D data will be described.
In this case, as shown in FIG. 5, the STL format data corresponding to the area-specific medical 3D data by performing surface model transformation on the area-specific medical 3D data acquired by dividing the medical 3D data into voxel areas. To create. Since the data in the STL format is surface data, the biological property information given to each voxel of the medical 3D data for each region is lost by performing the surface model transformation. Therefore, apart from the surface model transformation, 3D modeling biophysical property information including position information indicating the voxel position and biophysical property information given for each position information is created from the area-specific medical 3D data. The biological property information given for each position information is the biological property information associated with the voxel at the position indicated by the position information. That is, the modeling 3D data referred to in this description includes STL format data and 3D modeling biological property information.

(II) Generation of modeling 3D data including FAV format data A case of generating modeling 3D data including FAV (FAbricatable Voxel) format data based on medical 3D data will be described.
In this case, as shown in FIG. 6, the FAV format data corresponding to the area-specific medical 3D data is obtained by performing FAV format conversion on the area-specific medical 3D data acquired by dividing the medical 3D data into voxel areas. create. The FAV format data is defined as voxel data, not surface data like STL format data. As a result, medical 3D data, which is voxel data to which image density information, biological property information, and the like are attached, can be converted into FAV format data with image density information, biological characteristic information, and the like attached. That is, it is preferable in that it is possible to omit a step of separately processing data related to necessary information such as biological property information, such as when the data is converted into STL format data.

(3) Modeling Process The modeling method of the present invention includes a modeling process for modeling a three-dimensional model using a 3D printer based on medical 3D data of a living body. Further, as described above, in the present disclosure, "to model a three-dimensional model using a 3D printer based on the medical 3D data of a living body" means that the medical 3D data is input to the 3D printer to model the three-dimensional model. Not limited to the case of directly using medical 3D data, but indirectly medical 3D data such as inputting 3D data for modeling generated based on 3D medical data into a 3D printer to form a three-dimensional model. Is also used. Hereinafter, the modeling process will be described by taking as an example a case where 3D data for modeling generated based on medical 3D data is input to a 3D printer to model a three-dimensional model.

First, a case where 3D modeling data including the above STL format data is input to a 3D printer will be described. In this case, the modeling 3D data includes STL format data and 3D modeling biological property information. These data may be input at the same time or may be input separately.
The 3D printer converts the input STL format data into a 2D image data set for printing. The 2D image data set for printing is a data set including a plurality of 2D image data for printing, and the 2D image data for printing is to slice the data in STL format according to the resolution of the 3D printer in the Z-axis direction. It is the two-dimensional slice data obtained in. Next, the 3D printer adds strength physical property information indicating the strength physical property in each region of the printing 2D image data based on the input 3D modeling biological property information. Based on the strength physical property information in each region of the 2D image data for printing and the 2D image data for printing, the process of ejecting and curing a plurality of types of modeling compositions into a predetermined region with a predetermined discharge amount is repeated with a 3D printer. Thereby, it is possible to form a three-dimensional model having a distribution of strength physical characteristics corresponding to the distribution of biological characteristics. Here, in the present disclosure, the "strength physical property" represents the physical property of a three-dimensional model formed by a 3D printer, and specifically, it represents viscoelasticity because it is a physical property corresponding to the biological physical property.

Next, a case where 3D modeling data including the above FAV format data is input to the 3D printer will be described.
The 3D printer converts the input FAV format data into a 2D image data set for printing, which is the same slice data as described above. However, each print 2D image data included in the print 2D image data set is provided with strength physical property information indicating strength physical properties in each region based on the biological physical property information included in the FAV format data. Based on the strength physical property information in each region of the 2D image data for printing and the 2D image data for printing, the process of ejecting and curing a plurality of types of modeling compositions into a predetermined region with a predetermined discharge amount is repeated with a 3D printer. Thereby, it is possible to form a three-dimensional model having a distribution of strength physical characteristics corresponding to the distribution of biological characteristics.

As a 3D printer used in the modeling process, for example, by ejecting a plurality of types of modeling compositions into a predetermined area at a predetermined discharge amount, the strength and physical properties of the three-dimensional model to be modeled are controlled for each part. There are printers that can do it. Specific examples thereof include a material jetting method (MJ method) 3D printer that ejects a modeling composition with an inkjet head.

As described above, as a method of associating the strong physical characteristics with the biological physical properties by using a 3D printer, there is a method of using a 3D printer that can express the strong physical properties by gradation. Therefore, an example of this method will be described.
First, a high-strength modeling composition capable of modeling a three-dimensional model having high-strength physical characteristics and a low-strength modeling composition capable of modeling a three-dimensional model having low-strength physical properties are prepared. At least one type of each of these modeling compositions is used, but a plurality of types may be used for each. At this time, the strength of the three-dimensional model formed by the high-strength modeling composition is preferably equal to or higher than the maximum value of the biological property in the living body, and the strength of the three-dimensional model formed by the low-strength modeling composition. The physical properties are preferably not less than the minimum value of the biological properties in the living body.
Next, the strength and physical characteristics of the three-dimensional model are controlled by the pattern of the modeling composition arranged to fill a certain grid area. For example, as shown in FIG. 7, when it is necessary to express by the strength physical characteristics of 7 gradations, a combination pattern in which a grid with 6 sections as the minimum unit is filled with a high-strength modeling composition and a low-strength modeling composition is used. It is possible to express the intensity of 7 gradations. By increasing the number of sections of the unit grid, various gradation expressions become possible. By arranging it in the XY plane, it is possible to set the intensity distribution in the plane direction, and by arranging it in the Z direction, it is possible to set the intensity distribution in the vertical direction. Can be modeled. That is, in the present disclosure, the "distribution of the strength physical characteristics corresponding to the distribution of the biological characteristics" is not limited to the case where the strength physical characteristics in the distribution are the same as the biological properties at the corresponding positions, and is realized by the gradation expression. It also includes cases where the strength physical characteristics are close to the biological characteristics at the corresponding positions. Examples of the case of approximation include a case where the difference between the strength physical characteristics (synonymous with the model physical properties described later) with respect to the biological physical properties is within 5%. Further, in the present disclosure, the "gradation" is an arrangement pattern formed by arranging a plurality of types of modeling compositions, respectively, as described above, and the strength and physical characteristics of the cured product differ depending on the arrangement pattern. Represents a thing.
Since this method can be expressed as a voxel, it is efficient if it corresponds to a voxel format such as FAV. Further, the number of droplets of the modeling composition that fills the unit compartment may be any configuration.
In addition, by grasping the intensity physical properties at gradations that can be expressed by a 3D printer in advance by MRE measurement or the like, it is possible to more accurately model a three-dimensional model having a distribution of intensity physical properties corresponding to the distribution of biological properties. be able to.

(4) Evaluation Step The modeling method of the present invention may include an evaluation step for evaluating the accuracy of the modeled three-dimensional model. The evaluation process consists of biological property information indicating the biological characteristics acquired by measuring the living body by MRE in the acquisition process (specifically, the measurement step during the acquisition process) and the three-dimensional model (model) formed in the modeling process. ) Is a step of evaluating the accuracy of the modeled three-dimensional model based on the model physical property information indicating the model physical properties acquired by measuring MRE. This step may be executed by a person or by an information processing device such as a personal computer.

First, a method of evaluating the accuracy of a three-dimensional model formed based on biological physical property information and model physical property information will be described.
As a method for evaluating the accuracy of a three-dimensional model, for example, a method for evaluating the accuracy by determining whether the distribution of biological properties and the distribution of model physical properties show almost the same distribution, correspondence between living organisms and three-dimensional models. Examples thereof include a method of evaluating accuracy by determining whether or not the site has substantially the same biological and model physical characteristics.

The corresponding parts of the living body and the three-dimensional model are, for example, the parts in the living body, the parts in the three-dimensional model, and the living body that have almost the same coordinates when the coordinates are assigned to the living body and the three-dimensional model by the same standard. Examples thereof include a site having a specific structure inside (a tumor portion, etc.) and a site in a three-dimensional model imitating a site having the specific structure in a living body (a site imitating a tumor portion, etc.).
As an example of a criterion for determining whether or not the corresponding parts of the living body and the three-dimensional model have substantially the same biological characteristics and model physical characteristics, the difference between the model physical characteristics and the biological physical properties at the corresponding parts is within 5%. Can be mentioned. The difference is not limited to 5% or less, and can be appropriately selected depending on the degree of accuracy required. For example, the difference may be 50% or less, 40% or less, 30% or less, 20% or less, 10% or less. However, it is preferable that the difference is small from the viewpoint that high accuracy can be evaluated.

In addition, as described above, in order to compare the biological property information and the model physical property information at the corresponding parts of the living body and the model, the information indicating the position in the living body where the biological physical characteristics were measured and the three-dimensional model in which the model physical characteristics were measured were measured. It is also preferable that there is information indicating the position in the modeled object. Therefore, when evaluating the accuracy of a three-dimensional model, medical 3D data, which is information associated with boxel, image density information, and biological property information, and information associated with boxel, image density information, and model physical property information are used. It is preferable to use a certain model 3D data and compare the biological property information and the model physical property information contained in each of these data. This is because the voxel corresponds to the information indicating the above position. The model 3D data is data acquired in the same manner as the medical 3D data, and at least the model image data acquired by photographing the three-dimensional model with a medical imaging device and the three-dimensional model are MRE. It represents the model physical properties acquired by measurement and the data created based on it.

In this evaluation step, the model physical properties obtained by measuring the MRE of the three-dimensional model are used. This indicates that it is preferable that water suitable for MRE measurement using a hydrogen nucleus as a signal source is contained as one of the main components of the material constituting the three-dimensional model. That is, it is preferable that hydrogel as described later is contained as a material constituting the three-dimensional model.

2. 2. Modeling Composition The modeling composition used in the modeling process will be described. The modeling composition may be any composition that can be used in a 3D printer and can form a three-dimensional model having a distribution of strength physical characteristics corresponding to the distribution of biological characteristics, for example, an elastomer and a gel. Examples thereof include a composition as a precursor for modeling. Among these, as one of the main components of the constituent materials, a composition as a precursor for forming a hydrogel containing water as in the case of a living body (referred to as "hydrogel three-dimensional modeling composition") is preferable. .. Hereinafter, the hydrogel three-dimensional modeling composition will be described as an example of the modeling composition.

The hydrogel three-dimensional modeling composition contains water, a polymerizable compound, and may contain minerals, an organic solvent, and other components, if necessary.
In the present disclosure, the "hydrogel three-dimensional modeling composition" is a liquid composition that is cured by being irradiated with active energy rays such as light or heat to form a hydrogel, and is particularly a three-dimensional composition made of hydrogel. It means a liquid composition used for modeling a modeled object. Further, in the present disclosure, the "hydrogel" represents a structure in which water is contained in a three-dimensional network structure containing a polymer, and the three-dimensional network structure is formed by a composite of a polymer and a mineral. In the case of a three-dimensional network structure, it is particularly called "organic-inorganic composite hydrogel". The hydrogel contains water as a main component, and specifically, the water content is preferably 30.0% by mass or more with respect to the total amount of the hydrogel, and is 40.0% by mass or more. Is more preferable, and 50.0% by mass or more is further preferable.

(1) Water The hydrogel three-dimensional modeling composition contains water. The water is not particularly limited as long as it can be generally used as a solvent, and for example, pure water such as ion-exchanged water, ultra-filtered water, reverse osmosis water, distilled water, and ultrapure water are used. be able to.
The water content can be appropriately selected depending on the intended purpose. For example, when the hydrogel three-dimensional modeling composition is used for modeling an organ model, 30. It is preferably 0% by mass or more and 90.0% by mass or less, and more preferably 40.0% by mass or more and 90.0% by mass or less.
In addition, other components such as an organic solvent may be dissolved or dispersed in water depending on the purpose of imparting moisturizing property, antibacterial property, conductivity, hardness adjustment and the like.

(2) Polymerizable compound The composition for hydrogel three-dimensional modeling contains a polymerizable compound which is a compound having a polymerizable functional group. Examples of the polymerizable compound include monomers and oligomers. The polymerizable compound polymerizes by being irradiated with active energy rays or heat to form at least a part of the polymer. That is, the polymer has structural units derived from the polymerizable compound. Further, it is preferable that the polymer is crosslinked with a mineral and compounded to form a three-dimensional network structure in a hydrogel. Here, the polymerizable compound is preferably water-soluble. The term "water-soluble" means that, for example, when 100 g of water at 30 ° C. and 1 g of a monomer are mixed and stirred, 90% by mass or more of the monomer is dissolved.

The polymerizable compound is not particularly limited as long as it is a compound having a polymerizable functional group, but is preferably a compound having a photopolymerizable functional group. In the present disclosure, the "polymerizable functional group" means a functional group that causes a polymerization reaction by irradiation with active energy rays or the addition of heat, and the "photopolymerizable functional group" means a polymerization reaction particularly by irradiation with active energy rays. It means a functional group that causes. Examples of the photopolymerizable functional group include, but are not limited to, a (meth) acryloyl group, a group having an ethylenically unsaturated bond such as a vinyl group and an allyl group, and a cyclic ether group such as an epoxy group. .. Specific examples of the compound containing a group having an ethylenically unsaturated bond include, for example, a compound having a (meth) acrylamide group, a (meth) acrylate compound, a compound having a (meth) acryloyl group, a compound having a vinyl group, and an allyl. Examples include compounds having a group.

(I) Monomer The monomer that can be used as the polymerizable compound is preferably a compound having one or more polymerizable functional groups such as an unsaturated carbon-carbon bond, and examples thereof include monofunctional monomers and polyfunctional monomers. Further, examples of the polyfunctional monomer include a bifunctional monomer and a trifunctional or higher functional monomer. These may be used alone or in combination of two or more.

(A) Monofunctional monomer Examples of the monofunctional monomer include acrylamide, N-substituted acrylamide derivative, N, N-di-substituted acrylamide derivative, N-substituted methacrylicamide derivative, N, N-di-substituted methacrylicamide derivative, and acrylic acid. , 2-Ethylhexyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, caprolactone-modified tetrahydrofurfuryl (meth) acrylate, 3-methoxybutyl (meth) acrylate, tetrahydrofurfuryl ( Meta) 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 so on. These may be used alone or in combination of two or more. Among these, acrylamide, N, N-dimethylacrylamide, N-isopropylacrylamide, acryloylmorpholine, hydroxyethylacrylamide, isobornyl (meth) acrylate and the like are preferable.

The content of the monofunctional monomer is preferably 0.5% by mass or more and 30.0% by mass or less with respect to the total amount of the hydrogel three-dimensional modeling composition.

(B) Bifunctional Monomer 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 neo. Pentyl Glycol Hydroxypivalic Acid Ester Di (Meta) Acrylic, Hydroxy Pivalic Acid Neopentyl Glycol Ester Di (Meta) Acrylic, 1,3-Butanediol Di (Meta) Acrylic, 1,4-Butanediol Di (Meta) Aacrylate, 1, 6-Hexanediol di (meth) acrylate, 1,9-nonanediol di (meth) acrylate, diethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, tripropylene glycol di (meth) acrylate, caprolactone-modified hydroxy Neopentyl glycol ester di (meth) acrylate, propoxylated opentyl glycol di (meth) acrylate, ethoxy-modified bisphenol A di (meth) acrylate, polyethylene glycol 200 di (meth) acrylate, polyethylene glycol 400 di (meth) acrylate And so on. These may be used alone or in combination of two or more.

(C) Trifunctional or higher monomer Examples of the trifunctional or higher monomer include trimethylolpropanetri (meth) acrylate, pentaerythritol tri (meth) acrylate, dipentaerythritol hexa (meth) acrylate, triallyl isocyanurate, and ε. -Caprolactone-modified dipentaerythritol tri (meth) acrylate, ε-caprolactone-modified dipentaerythritol tetra (meth) acrylate, ε-caprolactone-modified dipentaerythritol penta (meth) acrylate, ε-caprolactone-modified dipentaerythritol hexa (meth) acrylate , Tris (2-hydroxyethyl) isocyanurate tri (meth) acrylate, ethoxylated trimethylol propantri (meth) acrylate, propoxylated trimethylol propantri (meth) acrylate, propoxylated glyceryl tri (meth) acrylate, pentaerythritol tetra. Examples thereof include (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, dipentaerythritol hydroxypenta (meth) acrylate, ethoxylated pentaerythritol tetra (meth) acrylate, and penta (meth) acrylate ester. These may be used alone or in combination of two or more.

The content of the polyfunctional monomer is preferably 0.01% by mass or more and 10.0% by mass or less with respect to the total amount of the hydrogel three-dimensional modeling composition.

(II) Oligomer The oligomer is a low polymer of the monofunctional monomer or a low polymer having a reactive unsaturated bond group at the terminal. These may be used alone or in combination of two or more.

(3) Minerals The hydrogel three-dimensional modeling composition preferably contains minerals. The mineral is not particularly limited as long as it is a mineral capable of binding to a polymer formed from the above polymerizable compound, and can be appropriately selected depending on the intended purpose. For example, a layered clay mineral, particularly a water-swellable layered mineral. Examples include clay minerals.
The water-swellable layered clay mineral will be described with reference to FIG. FIG. 8 is a schematic diagram showing an example of a state in which a water-swellable layered clay mineral as a mineral and a water-swellable layered clay mineral are dispersed in water. As shown in the upper figure of FIG. 8, the water-swellable layered clay mineral exists in a single layer state, and exhibits a state in which two-dimensional disk-shaped crystals having a unit cell in the crystal are stacked. Then, when the water-swellable layered clay mineral in the upper part of FIG. 8 is dispersed in water, each single layer is separated into a plurality of two-dimensional disk-shaped crystals as shown in the lower part of FIG.
As shown in FIG. 8, the water swelling property means that water molecules are inserted between each single layer of the layered clay mineral and dispersed in water. Further, the shape of the single layer of the water-swellable layered clay mineral is not limited to the disk shape, and may be another shape.

Examples of the water-swellable layered clay mineral include water-swellable smectite and water-swellable mica. More specifically, water-swellable hectorite containing sodium as an interlayer ion, water-swellable montmorillonite, water-swellable saponite, water-swellable synthetic mica and the like can be mentioned. These may be used alone or in combination of two or more. Among these, water-swellable hectorite is preferable because a highly elastic hydrogel can be obtained.
The water-swellable hectorite may be appropriately synthesized or may be a commercially available product. Examples of commercially available products include synthetic hectorite (Raponite XLG, manufactured by RockWood), SWN (manufactured by Coop Chemical Ltd.), and fluorinated hectorite SWF (manufactured by Coop Chemical Ltd.). Among these, synthetic hectorite is preferable from the viewpoint of improving the elastic modulus of the hydrogel.

The mineral content is preferably 1.0% by mass or more and 40.0% by mass or less with respect to the total amount of the hydrogel three-dimensional modeling composition.

(4) Organic solvent The hydrogel three-dimensional modeling composition may contain an organic solvent, if necessary. The organic solvent is contained, for example, for the purpose of enhancing the moisturizing property of the hydrogel.
Examples of the organic solvent include alkyl alcohols having 1 to 4 carbon atoms, amides, ketones, ketone alcohols, ethers, polyhydric alcohols, polyalkylene glycols, lower alcohol ethers of polyhydric alcohols, and alkanols. Examples thereof include amines and N-methyl-2-pyrrolidone. These may be used alone or in combination of two or more.
Among these, polyhydric alcohol is preferable from the viewpoint of moisturizing property, and specifically, ethylene glycol, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4. -Polyhydric alcohols such as butanediol, diethylene glycol, triethylene glycol, 1,2,6-hexanetriol, thioglycol, hexylene glycol and glycerin are favorably used.
The content of the organic solvent is preferably 10.0% by mass or more and 50.0% by mass or less with respect to the total amount of the hydrogel three-dimensional modeling composition. When it is 10.0% by mass or more, drying of the hydrogel three-dimensional modeling composition can be suppressed, and when it is 50.0% by mass or less, the dispersibility of minerals in the hydrogel three-dimensional modeling composition can be improved.

(5) Other components The hydrogel three-dimensional modeling composition may contain other components as needed.
The other components are not particularly limited and may be appropriately selected depending on the intended purpose. For example, a stabilizer, a surface treatment agent, a polymerization initiator, a colorant, a viscosity modifier, an adhesive-imparting agent, and an antioxidant. , Anti-aging agents, cross-linking agents, UV absorbers, plasticizers, preservatives, metal ions, fillers, metal microparticles, dispersants and the like.

(I) Stabilizer Stabilizer is contained to stably disperse minerals and maintain the sol state of the hydrogel three-dimensional modeling composition. Further, when the hydrogel three-dimensional modeling composition is used in a method of ejecting as droplets, a stabilizer is contained for the purpose of stabilizing the characteristics as a liquid.
Examples of the stabilizer include high-concentration phosphates, glycols, nonionic surfactants and the like.

(II) Surface Treatment Agent Examples of the surface treatment agent include polyester resin, polyvinyl acetate resin, silicone resin, kumaron resin, fatty acid ester, glyceride, and wax.

(III) Polymerization Initiator Examples of the polymerization initiator include a thermal polymerization initiator and a photopolymerization initiator. Among these, a photopolymerization initiator that generates radicals or cations by irradiating with active energy rays is preferable from the viewpoint of storage stability.
As the photopolymerization initiator, any substance that generates radicals by irradiation with light (particularly ultraviolet rays having a wavelength of 220 nm or more and 400 nm or less) can be used.
The thermal polymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. For example, an azo-based initiator, a peroxide initiator, a persulfate initiator, a redox (oxidation-reduction) initiator, etc. Can be mentioned.

(6) Physical Properties of Hydrogel Three-dimensional Modeling Composition The viscosity of the hydrogel three-dimensional modeling composition at 25 ° C. is preferably 3.0 mPa · s or more and 20.0 mPa · s or less, and 6.0 mPa · s or more and 12.0 mPa. -S or less is more preferable. When the viscosity is 3.0 mPa · s or more and 20.0 mPa · s or less, it can be suitably applied to droplet ejection in a 3D printer (particularly a material jetting method). The viscosity can be measured using, for example, a rotational viscometer (VISCOMATE VM-150III, manufactured by Toki Sangyo Co., Ltd.).

The surface tension of the hydrogel three-dimensional modeling composition is preferably 20 mN / m or more and 45 mN / m or less, and more preferably 25 mN / m or more and 34 mN / m or less. When the surface tension is 20 mN / m or more, the discharge stability can be improved, and when the surface tension is 45 mN / m or less, the hydrogel three-dimensional modeling composition can be easily filled in the discharge nozzle for modeling or the like. 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.).

3.3 Method of modeling a three-dimensional model using a 3D printer As an example of a method of modeling a three-dimensional model with a 3D printer (hereinafter, also referred to as "modeling device"), the above-mentioned hydrogel is used with a material jet 3D printer. A method of modeling a hydrogel three-dimensional model using a three-dimensional modeling composition will be described.

The method for forming a hydrogel three-dimensional object by the material jetting method is a liquid film forming step of applying droplets of the hydrogel three-dimensional modeling composition to form a liquid film, and a liquid film of the hydrogel three-dimensional modeling composition. It has a curing step of curing the above, and is characterized in that the liquid film forming step and the curing step are sequentially repeated. The method for modeling the hydrogel three-dimensional object may include, if necessary, a support modeling step for forming a support that supports the hydrogel three-dimensional object, and other steps.
The hydrogel three-dimensional modeling device by the material jetting method applies a storage means containing the hydrogel three-dimensional modeling composition and a droplet of the contained hydrogel three-dimensional modeling composition to a liquid. It has a liquid film forming means for forming a film and a curing means for curing the liquid film of the composition for hydrogel three-dimensional modeling, and is characterized in that the liquid film forming by the liquid film forming means and the curing by the curing means are sequentially repeated. And.

First, the material jetting method will be described with reference to FIGS. 9 and 10. FIG. 9 is a schematic view showing an example of a modeling device for a hydrogel three-dimensional model. FIG. 10 is a schematic view showing an example in which a hydrogel three-dimensional object is peeled off from a support. The material jetting type hydrogel three-dimensional modeling apparatus 10 shown in FIG. 9 uses a head unit in which inkjet heads are arranged, and accommodates the hydrogel three-dimensional modeling composition from the hydrogel three-dimensional modeling composition injection head unit 11. The hydrogel three-dimensional modeling composition contained in the container is supported by the support modeling composition injection head unit 12 to support the support modeling composition contained in the support modeling composition container. It is jetted toward the substrate 14, and the hydrogel three-dimensional modeling composition and the support modeling composition are laminated while being cured by an adjacent ultraviolet irradiator 13. Here, the composition for forming a support represents a liquid composition that is cured by being irradiated with active energy rays such as light or heat to form a support that supports a hydrogel three-dimensional model, for example. Examples include acrylic materials. The modeling device 10 may have a smoothing member 16 that flattens the sprayed hydrogel three-dimensional modeling composition.

The modeling device 10 includes a hydrogel three-dimensional modeling composition injection head unit 11, a support modeling composition injection head unit 12, an ultraviolet irradiator 13, a three-dimensional modeling object (hydrogel) 17, and a support (support material). In order to keep the gap with 18 constant, stacking is performed while lowering the stage 15 according to the number of stacking.

The ultraviolet irradiator 13 in the modeling apparatus 10 is used when moving in either the direction of the arrow A or B, and the heat generated by the ultraviolet irradiation smoothes the laminated surface, resulting in the dimensions of the three-dimensional model 17. Stability is improved.

After the modeling in the modeling device 10 is completed, the support 18 can be peeled off as a unit by pulling the three-dimensional model 17 and the support 18 in the horizontal direction as shown in FIG. 10, and the three-dimensional model 17 can be easily taken out. can.

(1) Liquid film forming step The method for applying the hydrogel three-dimensional modeling composition in the liquid film forming step is not particularly limited as long as the droplet can be applied to the target position with appropriate accuracy, and the purpose is It can be appropriately selected depending on the situation, and a known droplet ejection method can be used. Specific examples of the droplet ejection method include a dispenser method, a spray method, an inkjet method, and the like, but the inkjet method is preferable.

The volume of the droplets of the hydrogel three-dimensional modeling composition is, for example, preferably 2 pL or more and 60 pL or less, and more preferably 15 pL or more and 30 pL or less. When the volume of the droplet is 2 pL or more, the ejection stability can be improved, and when it is 60 pL or less, the filling is facilitated when the hydrogel three-dimensional modeling composition is filled in the ejection nozzle for modeling or the like.

(2) Curing Step Examples of the curing means for curing the liquid film of the hydrogel three-dimensional modeling composition in the curing step include an ultraviolet (UV) irradiation lamp and an electron beam. Examples of the type of ultraviolet (UV) irradiation lamp include a high-pressure mercury lamp, an ultra-high pressure mercury lamp, and a metal halide lamp.
UV-LED (Ultra Light-Light Emitting Diode) is preferably used as a curing means for the composition for hydrogel three-dimensional modeling. The emission wavelength of the LED is not particularly limited and is generally 365 nm, 375 nm, 385 nm, 395 nm, 405 nm, etc. However, considering the influence of color on the modeled object, the absorption of the initiator is increased. In addition, short wavelength light emission is more advantageous. Further, the UV-LED has a smaller amount of heat energy generated during curing and less heat damage to the hydrogel than a commonly used ultraviolet irradiation lamp (high pressure mercury lamp, ultrahigh pressure mercury lamp, metal halide lamp), electron beam, or the like. In particular, since the hydrogel formed by the hydrogel three-dimensional modeling composition is used in a state of containing water, this effect is remarkable.

The method for forming a hydrogel three-dimensional object is a liquid film forming step of applying droplets of the hydrogel three-dimensional modeling composition to form a liquid film, and a curing step of curing the liquid film of the hydrogel three-dimensional modeling composition. And, the liquid film forming step and the curing step are sequentially repeated. At this time, the number of repetitions is not particularly limited, and can be appropriately selected depending on the size, shape, and the like of the hydrogel three-dimensional model to be modeled. The average thickness per layer after curing is preferably 10 μm or more and 50 μm or less. When the average thickness is 10 μm or more and 50 μm or less, it is possible to perform modeling with high accuracy and less peeling.

(3) Support modeling process The support modeling composition used in the support modeling process is cured by being irradiated with active energy rays such as light or heat, and supports the hydrogel three-dimensional model. It is a liquid composition for modeling. The composition of the support modeling composition is different from that of the hydrogel three-dimensional modeling composition. Specifically, it preferably contains a curable material, a polymerization initiator and the like, and does not contain water and minerals. Examples of the curable material are compounds that are cured by causing a polymerization reaction by irradiation with active energy rays (ultraviolet rays, electron beams, etc.), heating, and the like, and examples thereof include active energy ray-curable compounds and thermosetting compounds. Among these, a material that is liquid at room temperature is preferable.
The support modeling composition is applied at a position different from that of the hydrogel three-dimensional modeling composition. This means that the composition for forming the support and the composition for forming the hydrogel three-dimensionally do not overlap with each other, and the composition for forming the support and the composition for forming the hydrogel three-dimensionally may be adjacent to each other.
As a method of applying the composition for supporting support, the same method as the method of applying the composition for hydrogel three-dimensional modeling can be mentioned.

(4) Other Steps Other steps include, for example, a step of smoothing the liquid film, a peeling step, a step of polishing a three-dimensional model, a step of cleaning a three-dimensional model, and the like, and a step of smoothing the liquid film. It is preferable to include. This is because the liquid film formed in the liquid film forming step does not always have the target film thickness (layer thickness) at all positions. For example, when a liquid film is formed by an inkjet method, non-ejection or a step between dots may occur, and it may be difficult to form a highly accurate three-dimensional model. To solve these problems, the liquid film is mechanically smoothed (leveled) after being formed, the hydrogel thin film obtained by curing the liquid film is mechanically scraped off, and the smoothness is detected and the next layer is used. It is conceivable to adjust the amount of film formation at the dot level at the time of laminating. When the hydrogel three-dimensional model is modeled for an organ model, the hardness of the hydrogel is relatively soft, so a method of mechanically leveling the liquid film is preferable as a smoothing method. Examples of the method of mechanically smoothing include a method of leveling with a blade-shaped member and a method of leveling with a roller-shaped member.

(5) Method for modeling a hydrogel three-dimensional model having parts with different strength physical characteristics Next, as a more specific explanation of a method for modeling a hydrogel three-dimensional model, a hydrogel three-dimensional model having parts with different strength physical properties An example of a modeling method will be described. In the following description, an embodiment using two types of hydrogel three-dimensional modeling compositions having different compositions will be described in detail as an example, but the present invention is not limited to such an embodiment. Those skilled in the art can easily understand further embodiments (for example, embodiments using three or more types of hydrogel three-dimensional modeling compositions) from the above description.

In the method of forming a hydrogel three-dimensional model having parts having different strength properties, a liquid film having a plurality of regions having different compositions is formed by applying droplets of a plurality of hydrogel three-dimensional modeling compositions having different compositions. It has a liquid film forming step of forming and a curing step of curing the liquid film, and is characterized in that the liquid film forming step and the curing step are sequentially repeated.
In the above-mentioned modeling method, a storage means containing a plurality of hydrogel three-dimensional modeling compositions having different compositions and a droplet of a plurality of hydrogel three-dimensional modeling compositions having different compositions are contained. By imparting, it has a liquid film forming means for forming a liquid film having a plurality of regions having different compositions and a curing means for curing the liquid film, and the liquid film forming means for forming the liquid film and the curing means for curing the liquid film. A hydrogel three-dimensional object modeling device, which is characterized by repeating the above steps in sequence, is used.
Specifically, first, a first hydrogel three-dimensional modeling composition and a second hydrogel three-dimensional modeling composition having a composition different from that of the first hydrogel three-dimensional modeling composition are used, respectively. By controlling the position and amount of each of the droplets of the hydrogel three-dimensional modeling composition to be applied, a liquid film having a plurality of regions having different compositions is formed. The first hydrogel three-dimensional modeling composition is an example of the above-mentioned high-strength modeling composition, and the second hydrogel three-dimensional modeling composition is an example of the above-mentioned low-strength modeling composition. And. Next, this liquid film is cured to form a cured film for one layer having the above-mentioned regions continuously. After that, the cured film is laminated by repeating the formation and curing of the liquid film in sequence, and a hydrogel three-dimensional model having a plurality of sites having different strength and physical characteristics is formed. It should be noted that a plurality of sites having different strength physical properties in the hydrogel three-dimensional model may be present due to the difference in strength physical properties in one layer of the cured film, or due to the difference in strength physical properties between the cured films. It may exist.

4. Uses of the three-dimensional model The use of the three-dimensional model includes, for example, a tissue model that imitates the tissue of a living body, and a human tissue model is preferable. Here, the tissue is a functional organ constituting a living body. Therefore, the tissue is not limited to the internal organs, but includes all organs constituting the living body such as bones, skin, and blood vessels. Moreover, the tissue model is preferably an organ model.
The uses of the organ model can be roughly divided into two. One is an organ model for general-purpose use, and the other is an organ model for individual use. The organ model for general-purpose use is, for example, an organ model used for performance confirmation, calibration, training, structural confirmation in an educational field, etc. in medical device development. The organ model in this case has the average shape and physical properties of the target organ. Further, the organ model in this case is preferably a model that is modeled mainly based on the data of healthy subjects and the data of a single person or a plurality of people are averaged. The organ model for individual use is, for example, an organ model used for informed consent, preoperative simulation, surgical training, etc. in a medical field. The organ model in this case has the shape and physical properties of the organ including the affected part of the individual target patient. Further, the organ model in this case is preferably a model in which the affected part is reproduced by modeling based on the individual data of the patient.
When the three-dimensional model is used as a human organ model, the water content in the material such as hydrogel forming the three-dimensional model is preferably 70% by mass or more and 85% by mass or less with respect to the total amount of the three-dimensional model. .. When it is 70% by mass or more and 85% by mass or less, the water content can be the same as that of an actual human organ targeted by a human organ model, and can be suitably used. Specifically, it is preferably about 80% by mass in the case of a human heart model, preferably about 83% by mass in the case of a human kidney model, and it may be a human brain or intestinal model. It is preferably about 75% by mass. Therefore, the water content in the three-dimensional model is more preferably 75% by mass or more and 83% by mass or less with respect to the total amount of the three-dimensional model.

Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples.

<Preparation of composition A for high-strength modeling>
First, degassed with ion-exchanged water under reduced pressure for 30 minutes to prepare pure water, and while stirring 580.0 parts by mass of this pure water, synthetic hectorite (Raponite RD, BYK), which is a water-swellable clay mineral, is used. (Manufactured by) 67.0 parts by mass was added little by little and further stirred to prepare a mixed solution. Next, 5.0 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) as a dispersant for synthetic hectorite was added to the mixed solution to obtain a dispersion.
Next, 262.0 parts by mass of dimethylacrylamide (DMAA, manufactured by Tokyo Chemical Industry Co., Ltd.) from which the polymerization inhibitor had been removed by passing through a column of activated alumina was added to the obtained dispersion as a monomer. As a cross-linking agent, N, N'-methylenebisacrylamide (MBAA, manufactured by Tokyo Kasei Kogyo Co., Ltd.) 2.4 parts by mass, polyethylene glycol diacrylate (A-400, manufactured by Shin-Nakamura Chemical Industry Co., Ltd.) 8.0% by mass. Parts were added. Further, 300.0 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) was added and mixed as a drying inhibitor.
Next, 6.7 parts by mass of N, N, N', N'-tetramethylethylenediamine (TEMED, manufactured by Tokyo Chemical Industry Co., Ltd.) was added as a polymerization accelerator. Further, 5.3 parts by mass of Emargen LS-106 (manufactured by Kao Corporation) was added and mixed as a surfactant.
Next, while cooling in an ice bath, 12.3 parts by mass of a 4% by mass solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) was added, and after stirring and mixing, degassing under reduced pressure was carried out for 20 minutes. .. Subsequently, filtration was performed to remove impurities and the like to obtain a homogeneous high-strength modeling composition A.

-Measurement of viscoelasticity of the cured product of high-strength modeling composition A-
First, a hydrogel was prepared using the high-strength modeling composition A. Specifically, a container of 31 mm × 31 mm (thickness 10 mm) is prepared, the inside is filled with the high-strength modeling composition A, and an ultraviolet irradiator (SPOT CURE SP5-250DB manufactured by Ushio, Inc.) is used. It was cured. The irradiation conditions were wavelength: 365 nm, irradiation intensity: 350 mJ / cm ² , and irradiation time: 60 seconds.
Next, when the physical properties of the produced hydrogel were measured with a leometer, the storage elastic modulus was 8320 Pa and the loss elastic modulus was 2540 Pa.

<Preparation of composition B for low-strength modeling>
First, degassed with ion-exchanged water under reduced pressure for 30 minutes to prepare pure water, and while stirring 580.0 parts by mass of this pure water, synthetic hectorite (Raponite RD, BYK), which is a water-swellable clay mineral, is used. (Manufactured by) 67.0 parts by mass was added little by little and further stirred to prepare a mixed solution. Next, 5.0 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) as a dispersant for synthetic hectorite was added to the mixed solution to obtain a dispersion.
Next, 262.0 parts by mass of dimethylacrylamide (DMAA, manufactured by Tokyo Chemical Industry Co., Ltd.) from which the polymerization inhibitor had been removed by passing through a column of activated alumina was added to the obtained dispersion as a monomer. As a cross-linking agent, N, N'-methylenebisacrylamide (MBAA, manufactured by Tokyo Kasei Kogyo Co., Ltd.) 0.6 parts by mass, polyethylene glycol diacrylate (A-400, manufactured by Shin Nakamura Chemical Industry Co., Ltd.) 2.0 mass by mass. Parts were added. Further, 300.0 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) was added and mixed as a drying inhibitor.
Next, 6.7 parts by mass of N, N, N', N'-tetramethylethylenediamine (TEMED, manufactured by Tokyo Chemical Industry Co., Ltd.) was added as a polymerization accelerator. Further, 5.3 parts by mass of Emargen LS-106 (manufactured by Kao Corporation) was added and mixed as a surfactant.
Next, while cooling in an ice bath, 12.3 parts by mass of a 4% by mass solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) was added, and after stirring and mixing, degassing under reduced pressure was carried out for 20 minutes. .. Subsequently, filtration was performed to remove impurities and the like to obtain a homogeneous low-strength modeling composition B.

-Measurement of viscoelasticity of the cured product of composition B for low-strength modeling-
First, a hydrogel was prepared using the low-strength modeling composition B. Specifically, a container of 31 mm × 31 mm (thickness 10 mm) is prepared, the inside is filled with the low-strength modeling composition B, and an ultraviolet irradiator (SPOT CURE SP5-250DB manufactured by Ushio, Inc.) is used. It was cured. The irradiation conditions were wavelength: 365 nm, irradiation intensity: 350 mJ / cm ² , and irradiation time: 60 seconds.
Next, when the physical properties of the produced hydrogel were measured with a leometer, the storage elastic modulus was 4415 Pa and the loss elastic modulus was 3104 Pa.

<Acquisition of medical 3D data>
Using an MRI device capable of MRE measurement, medical 3D data including the liver portion of a patient suffering from fatty liver was acquired. The medical 3D data was created based on the medical image data acquired by photographing the patient with an MRI apparatus and the biological characteristics acquired by measuring the patient by MRE. Specifically, the medical 3D data includes a plurality of voxels created based on the medical image data, image density information indicating the image density (MRI signal value) in the medical image data assigned to each voxel, and voxels. It included biophysical property information indicating biophysical properties (viscous elasticity) given for each.
The biological characteristics (viscoelasticity) in the liver portion obtained by MRE measurement are the viscoelasticity in the cured product of the high-strength modeling composition A and the cured product of the low-strength modeling composition B at any site. It was within the range of viscoelasticity.

<Generation of 3D data for modeling>
First, the medical 3D data was divided into voxel regions, and the regional medical 3D data showing the liver portion was acquired. Next, FAV format data, which is 3D data for modeling, was created by performing FAV format conversion on the medical 3D data for each area.

<Example of liver model modeling>
The high-strength modeling composition A and the low-strength modeling composition B are each housed in a 3D printer having a material jetting method as shown in FIG. 9 and capable of expressing gradation of high-strength physical properties, and are stored in a 3D printer. Filled in the inkjet head of. Next, 3D data for modeling was input to a 3D printer, and based on the 3D data for modeling, a liver model, which is a three-dimensional model having a distribution of strength physical properties corresponding to the distribution of biological characteristics, was modeled. Specifically, each modeling composition was sprayed from an inkjet head, and liquid film formation and curing were sequentially repeated for modeling.

10 Modeling device 11 Hydrogel composition injection head unit for three-dimensional modeling 12 Composition injection head unit for support modeling 13 Ultraviolet irradiator 14 Modeling body support substrate 15 Stage 16 Smoothing member 17 Three-dimensional model (hydrogel)
18 Support (support material)

JP-A-2015-069054

Claims (5)

It is a modeling method having a modeling process of modeling a three-dimensional model using a 3D printer based on medical 3D data of a living body.
The medical 3D data is created based on the medical image data acquired by photographing the living body with a medical imaging device and the biological characteristics acquired by measuring the living body by MRE.
The three-dimensional model is a modeling method characterized by having a distribution of strength physical properties corresponding to the distribution of biological properties. The medical 3D data includes a plurality of voxels created based on the medical image data, image density information indicating the image density in the medical image data given to each voxel, and the biological property given to each voxel. The modeling method according to claim 1, further comprising biological property information indicating. The modeling method according to claim 1 or 2, wherein the 3D printer is a material jetting method. The modeling method according to any one of claims 1 to 3, which contains hydrogel as a material constituting the three-dimensional model. The modeling method according to any one of claims 1 to 4, wherein the biological physical characteristics and the strong physical characteristics are viscoelastic.

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