Patient-specific multi-material bionic tumor organ model and preparation method thereof

Abstract

The invention relates to a patient-specific multi-material bionic tumor organ model and a preparation method thereof. The method comprises the following steps: carrying out separation and three-dimensional modeling on different anatomical structures in an organ of a patient based on medical image data through an image segmentation technology. And establishing a corresponding relationship between the medical image data and different anatomical structures in the organ of the patient based on a three-dimensional modeling result, and restoring three-dimensional information of the tumor. And performing biomechanical measurement on each biological tissue in the general specimen corresponding to the organ of the patient to obtain a biomechanical measurement result of each biological tissue. And performing structure layering on a three-dimensional modeling result based on a biomechanical measurement result, and mapping a plurality of layered tissue areas with a plurality of printing materials matched with biomechanical properties. And preparing an initial bionic model based on the selected printing material and the biomechanical measurement result corresponding to each biological tissue by adopting a 3D printing technology, and post-processing and assembling the initial bionic model to obtain the bionic tumor organ model.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering and 3D printing technology, and in particular to a patient-specific multi-material biomimetic tumor organ model and its preparation method. Background Technology

[0002] Minimally invasive surgery (MIS), with its significant advantages such as less trauma, faster recovery, and fewer postoperative complications, has become the mainstream development direction of modern surgery. However, MIS differs significantly from traditional open surgery in terms of operation methods, field of vision acquisition, and hand-eye coordination, placing higher demands on surgeons' operational skills, spatial awareness, and surgical planning abilities. Particularly in tumor resection surgery, precise separation of tumor tissue and identification and protection of important vascular structures are crucial, but most existing training models cannot provide detailed three-dimensional anatomical information and realistic biomechanical feedback, hindering surgeons' spatial awareness training and accurate judgment of cutting boundaries.

[0003] Currently, the main methods used by surgeons to learn tumor resection and complex MIS (minor intraepithelial neoplasia) surgery include animal models, cadaver models, computer virtual reality (VR) simulators, traditional artificial material models, and 3D printed models. However, these existing methods generally have certain limitations. For example, while animal models have a certain degree of realism in anatomical structure and physiological responses, their drawbacks include the need for anesthesia support, complex ethical approval processes, and high maintenance costs, making them difficult to widely promote and apply to routine teaching and training. Cadaver models, on the other hand, possess a high degree of anatomical realism and tactile feedback, but their disadvantages include limited cadaver sources, stringent preservation conditions, and extremely high operating costs, making them difficult to become a universally applicable solution for routine training.

[0004] While computer virtual reality (VR) simulators can provide intuitive 3D structures and highly interactive simulation environments, supporting the simulation of various complex scenarios, their main drawback lies in the lack of realistic tactile feedback, tissue tension, and instrument feedback—key physical properties that make them difficult to completely replace the sensory training of tissue feel in real-world operations. Traditional artificial material models, such as existing tumor organ models, are mostly made of single or limited materials like silicone and rubber. Although they can achieve basic instrument operation training or theoretical teaching, when simulating crucial steps such as tumor resection, tissue separation, and vascularization, the mismatch between the material's mechanical properties and real tissue makes it impossible to provide realistic feel and feedback. This hinders effective training for doctors to judge tumor boundaries and perform precise resection.

[0005] Furthermore, existing 3D-printed organ models generally suffer from the problem of using a single material and lacking tissue layering. They mainly use single or a few materials such as photosensitive resin, polylactic acid (PLA), and silicone. These materials cannot simultaneously simulate the hard texture of real tumor tissue, the elasticity and toughness of normal organ tissue, and the flexibility of blood vessels. As a result, the tactile feel of the models is far from meeting the requirements of real surgery, making it difficult to achieve the realistic tactile feel and tissue layering needed for surgical training. Secondly, traditional 3D-printed models mostly lack simulation of blood vessels and pathological features. They can only reproduce the macroscopic anatomical morphology of organs, but lack key pathological features such as detailed vascular systems, clear tumor boundaries, and irregular lesion areas. This makes it impossible for the models to realistically simulate training for critical operations such as bleeding control, precise tumor demarcation, and identification and protection of important structures during surgery. Furthermore, due to the mismatch in mechanical properties, the mechanical properties of real organs (such as the fact that tumor tissue is usually hard, healthy tissue is relatively soft, and blood vessels are elastic and not easily torn) cannot be accurately reproduced through a single material or simple printing method. This mismatch in mechanical properties results in an unrealistic feel in the training models, failing to effectively cultivate doctors' perception of tissue characteristics. Finally, existing 3D printed models are usually based on standardized design and manufacturing, which has the problem of insufficient personalization. It is difficult to customize printing according to the specific medical images of patients (such as computed tomography CT scans and magnetic resonance imaging MRI), which limits its application value in individualized surgical training and preoperative planning.

[0006] In summary, existing technologies for preparing biomimetic models still have certain shortcomings in terms of realistic tactile feel, multi-material layering, simulation of blood vessels and pathological features, mechanical property matching, personalized customization, acquisition costs, and ethical constraints. These shortcomings result in poor fidelity to various biological tissues in the final biomimetic models, thereby reducing their reference value in practical applications. Summary of the Invention

[0007] The present invention aims to provide a patient-specific multi-material biomimetic tumor organ model and its preparation method to overcome the shortcomings of the prior art. The technical problem to be solved by the present invention is achieved through the following technical solution.

[0008] The first aspect of this invention provides a method for preparing a patient-specific multi-material biomimetic tumor organ model, the method comprising: Image segmentation technology is used to perform three-dimensional reconstruction based on medical image data in order to separate and model different anatomical structures within the patient's organs in three dimensions. Based on the 3D modeling results, a correspondence is established between the medical imaging data and different anatomical structures within the patient's organs to reconstruct the 3D information of the tumor. Biomechanical measurements were performed on each biological tissue in the gross specimen corresponding to the patient's organ to obtain the biomechanical measurement results of each biological tissue. Based on the biomechanical measurement results of each biological tissue, the three-dimensional modeling results are structurally layered, and the multiple layered tissue regions are mapped with a variety of printing materials that match the biomechanical properties in order to determine the printing materials. An initial biomimetic model was prepared using 3D printing technology based on selected printing materials and biomechanical measurement results corresponding to various biological tissues. The initial biomimetic model was then post-processed and assembled to obtain a biomimetic tumor organ model.

[0009] In one embodiment, the medical imaging data is computed tomography and magnetic resonance imaging images containing three-dimensional information of the patient's organs and tumor tissue; The three-dimensional information includes the tumor's boundaries, size, shape, location within the patient's organs, and the pathological relationship between the tumor and the surrounding vascular network and normal tissue.

[0010] In one embodiment, the step of performing three-dimensional reconstruction based on medical image data using image processing software to separate and model different anatomical structures within the patient's organs in three dimensions includes: The patient's medical imaging data is collected, and Mimics® software is used to separate different anatomical structures within the patient's organs based on the medical imaging data, thereby obtaining three-dimensional information of each anatomical structure within the patient's organs. Three-dimensional reconstruction is performed based on the three-dimensional information of various anatomical structures within the patient's organs to obtain the three-dimensional modeling results; The anatomical structures mentioned include the tumor solid, blood vessels, organ parenchyma, fat layer, and pathological features.

[0011] In one embodiment, the biomechanical measurement of each biological tissue in the gross specimen corresponding to the patient's organ, to obtain the biomechanical measurement results of each biological tissue, includes: Select gross specimens corresponding to the patient's organs, and use biomechanical measuring instruments to test the mechanical properties of each biological tissue in the gross specimens in order to determine the various test indicators in the biomechanical measurement results. The biological tissues mentioned include tumor tissue, organ parenchyma, blood vessel wall, adipose tissue, and connective tissue.

[0012] In one embodiment, the three-dimensional modeling results are structurally layered based on the biomechanical measurement results of each biological tissue. The multiple layered tissue regions are then mapped to various printing materials with matching biomechanical properties to determine the printing materials, including: Based on the various test indicators in the biomechanical measurement results, the biomechanical characteristics of different biological tissues are determined, and the three-dimensional modeling results are structurally layered according to the biomechanical characteristics to obtain multiple tissue regions; The tissue region is composed of a tumor region, a healthy tissue region, a blood vessel region, and a fat region.

[0013] In one embodiment, the step of structurally stratifying the three-dimensional modeling results based on biomechanical measurement results of various biological tissues, mapping the stratified tissue regions to multiple printing materials with biomechanical properties to determine the printing materials, further includes: Selected materials whose biomechanical properties match the biomechanical characteristics, as well as mixed materials combining multiple materials in proportion, are selected from the material library; Based on the biomechanical characteristics, different biological tissues are mapped to the candidate materials and hybrid materials to obtain the matching results between biological tissues and printing materials.

[0014] In one embodiment, the initial biomimetic model is prepared using 3D printing technology based on selected printing materials and biomechanical measurement results corresponding to various biological tissues. The initial biomimetic model is then post-processed and assembled to obtain a biomimetic tumor organ model, including: Based on the biomechanical properties of the printing material, a variety of 3D printing technologies are selected and combined. Based on the printing material and the 3D modeling results, the initial biomimetic model is obtained by combining and applying the various 3D printing technologies.

[0015] In one embodiment, the process of preparing an initial biomimetic model using 3D printing technology based on selected printing materials and biomechanical measurement results corresponding to various biological tissues, and then post-processing and assembling the initial biomimetic model to obtain a biomimetic tumor organ model, further includes: Based on the visual characteristics of each biological tissue in the three-dimensional modeling results, the initial biomimetic model is painted and stained. The cavities and tissue regions in the initial biomimetic model are filled to obtain the biomimetic tumor organ model.

[0016] In one embodiment, the method further includes: Based on the biomimetic tumor organ model, a flow test is performed on the vascular network in the biomimetic tumor organ model to determine whether there is any blockage in the vascular cavities of the vascular network. Simulated blood is filled into the vascular cavity by a liquid pump device, and the vascular network in the biomimetic tumor organ model is determined to be free of blockage when the blood is flowing. Otherwise, the location of the blockage in the vascular cavity is detected and the biomimetic tumor organ model is adjusted.

[0017] The second aspect of the present invention provides a patient-specific multi-material biomimetic tumor organ model, which is prepared by the method for preparing a patient-specific multi-material biomimetic tumor organ model as described in any one of the first aspects.

[0018] The present invention provides a patient-specific multi-material biomimetic tumor organ model and its preparation method, which has the following advantages compared with the prior art: (1) This invention uses image segmentation technology to separate and model different anatomical structures in a patient’s organs based on medical imaging data. Then, based on the results of the three-dimensional modeling, it establishes the correspondence between medical imaging data and different anatomical structures in a patient’s organs, effectively restoring the three-dimensional information of the tumor and laying the foundation for subsequent 3D printing and the authenticity of the prepared tumor model.

[0019] (2) This invention involves performing biomechanical measurements on various biological tissues in a gross specimen corresponding to a patient's organ, and then structurally stratifying the 3D modeling results based on the biomechanical measurement results of each biological tissue. Multiple tissue regions after stratification are mapped to various printing materials with matching biomechanical properties to determine the printing material. Finally, an initial biomimetic model is prepared using 3D printing technology based on the selected printing material and the biomechanical measurement results corresponding to each biological tissue. The initial biomimetic model is then post-processed and assembled to obtain the final biomimetic tumor organ model. The prepared biomimetic tumor organ model combines various biomechanical tests of the gross specimen with material selection based on biomechanical properties, making the final prepared biomimetic tumor organ model closer to the original tumor organ with a higher degree of fidelity, and improving the reference value of the tumor model in practical applications. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of the preparation method of a patient-specific multi-material biomimetic tumor organ model provided by the present invention; Figure 2 This is a schematic diagram of the overall process for preparing a patient-specific multi-material biomimetic tumor organ model in a specific embodiment of the present invention. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on the other component or there may be an intermediate component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intermediate component present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this specification are for illustrative purposes only and do not represent the only possible implementation.

[0024] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0025] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature and the second feature are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0026] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used in this specification includes any and all combinations of one or more of the associated listed items.

[0027] The following is combined Figures 1-2This invention describes a patient-specific multi-material biomimetic tumor organ model and its preparation method.

[0028] like Figure 1 As shown, in one embodiment, a method for preparing a patient-specific multi-material biomimetic tumor organ model includes the following steps: Step S110: Using image segmentation technology, three-dimensional reconstruction is performed based on medical image data to separate and model different anatomical structures within the patient's organs in three dimensions.

[0029] Among them, medical imaging data consists of computed tomography (CT) scans and magnetic resonance imaging (MRI) images containing three-dimensional information of the patient's organs and tumor tissues.

[0030] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention includes the following steps in step S110: Step S111: Collect the patient's medical imaging data and call Mimics® software to separate different anatomical structures in the patient's organs based on the medical imaging data to obtain three-dimensional information of each anatomical structure in the patient's organs.

[0031] Step S112: Perform three-dimensional reconstruction based on the three-dimensional information of various anatomical structures within the patient's organs to obtain three-dimensional modeling results.

[0032] The anatomical structures include the tumor solid, blood vessels, organ parenchyma, fat layer, and pathological features.

[0033] Step S120: Based on the 3D modeling results, establish the correspondence between medical imaging data and different anatomical structures within the patient's organs to reconstruct the 3D information of the tumor.

[0034] The three-dimensional information includes the tumor's boundaries, size, shape, location within the patient's organs, and the pathological relationship between the tumor and the surrounding vascular network and normal tissue.

[0035] Combine Figure 2 As shown in the specific embodiment, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention includes steps 1 to 5: Step 1: Medical image acquisition and 3D modeling.

[0036] Includes the following steps: Step 1.1, Patient image data acquisition.

[0037] Specifically, medical imaging data of patients scheduled for surgery are collected, including but not limited to computed tomography (CT) and / or magnetic resonance imaging (MRI) data. This imaging data contains precise three-dimensional information on the macroscopic anatomical structure of the patient's individual organs (such as liver, kidneys, lungs, pancreas, gastrointestinal tract, etc.), the tumor entity, and tissues closely related to the tumor, such as vascular networks, nerves, lymph nodes, and fat.

[0038] Step 1.2, 3D reconstruction and structural separation.

[0039] Specifically, professional image processing and 3D reconstruction software (such as, but not limited to, Mimics® software) is used to perform high-precision 3D reconstruction of the acquired CT / MRI image data. During this process, image segmentation technology is used to accurately separate different anatomical structures within the patient's organs, including but not limited to: tumor solids, blood supply vessels, draining vessels, normal organ parenchyma (such as liver parenchyma, kidney parenchyma, etc.), fat layer, and other possible pathological features (such as necrotic areas, calcifications, etc.).

[0040] Step 1.3, Reconstruction of 3D shape and position.

[0041] Specifically, through 3D reconstruction, the true boundaries, size, and shape of the tumor are accurately restored, as well as its precise location within the organ and its relationship with the surrounding vascular network and normal tissues. The restoration process ensures the accuracy of geometric dimensions through calibration (i.e., establishing a correspondence between medical image pixel values ​​and actual physical dimensions).

[0042] Step S130: Perform biomechanical measurements on each biological tissue in the gross specimen corresponding to the patient's organ to obtain the biomechanical measurement results of each biological tissue.

[0043] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention includes the following steps in step S130: Step S131: Select a gross specimen corresponding to the patient's organ, and use a biomechanical measuring instrument to test the mechanical properties of each biological tissue in the gross specimen in order to determine the various test indicators in the biomechanical measurement results.

[0044] Among them, biological tissues include tumor tissue, organ parenchyma, blood vessel walls, adipose tissue, and connective tissue.

[0045] Combine Figure 2 As shown in the specific embodiment, the present invention provides a method for preparing a patient-specific multi-material biomimetic tumor organ model, step 2, tissue measurement and structural layering design. This includes the following steps: Step 2.1, determination of biomechanical properties.

[0046] Specifically, for fresh gross specimens corresponding to organs (e.g., fresh organs from animals such as pigs and cattle, or ethically approved human organ donation specimens), professional biomechanical testing instruments (e.g., universal testing machines, hardness testers, tactile sensor arrays, etc.) are used to test the mechanical properties of different biological tissue components within the specimens. Test subjects include, but are not limited to: tumor tissue (if available), healthy organ parenchyma, major blood vessel walls, adipose tissue, connective tissue, etc. Test indicators include, but are not limited to: Young's modulus (elastic modulus), hardness, tensile strength, tear strength, Poisson's ratio, yield strength, creep characteristics, etc.

[0047] Step 2.2, structural layering and material mapping.

[0048] Specifically, based on the biomechanical characteristics of different tissues obtained from measurements, the previously obtained three-dimensional reconstructed patient organ models are precisely structurally stratified. This stratification divides the organ into regions with different biomechanical properties, for example: Tumor areas typically have high hardness; Healthy tissue areas: relatively soft and elastic; Vascular areas: possess high toughness and elasticity; Fatty areas: have lower density and softer texture.

[0049] Finally, the regions defined above are mapped to a variety of alternative printing materials with matching biomechanical properties.

[0050] Step S140: Based on the biomechanical measurement results of each biological tissue, the three-dimensional modeling results are structurally layered, and the multiple layered tissue regions are mapped with a variety of printing materials that match the biomechanical properties to determine the printing materials.

[0051] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention includes the following steps in step S140: Step S141: Based on the various test indicators in the biomechanical measurement results, determine the biomechanical characteristics of different biological tissues, and perform structural stratification on the three-dimensional modeling results according to the biomechanical characteristics to obtain multiple tissue regions.

[0052] The tissue region is composed of the tumor region, the healthy tissue region, the blood vessel region, and the fat region.

[0053] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention further includes the following steps in step S140: Step S142: Select selected materials whose biomechanical properties match their biomechanical characteristics, as well as mixed materials that combine multiple materials in proportion, from the material library.

[0054] Step S143: Map different biological tissues to candidate materials and mixed materials according to biomechanical characteristics to obtain the matching results between biological tissues and printing materials.

[0055] Combine Figure 2 As shown in the specific embodiment, the present invention provides a method for preparing a patient-specific multi-material biomimetic tumor organ model. Step 3 involves multi-material 3D printing. Based on the above-mentioned structural layering and material mapping results, various 3D printing technologies and processes are used to prepare tissues or structures with different biomechanical characteristics. This printing method and material selection achieve layered mechanical properties and fine structural reproduction of the model. The method includes the following steps: Step 3.1, Material Selection.

[0056] Specifically, appropriate printing materials are selected based on the biomechanical properties of different tissues (tumors, healthy tissues, blood vessels, adipose layer). These materials can be single materials, combinations of multiple materials, or mixtures in different proportions. These materials include, but are not limited to: (1) Used to simulate tumors, healthy tissues, etc.: acrylic acid, acrylamide (AAm), hydroxypropyl acrylate (HPA), polyvinylpyrrolidone polyethyleneimine (PEI), poly(2-ethyl-2-oxazoline) (PEOZ), polyvinylpyrrolidone (PVP), hydroxymethyl cellulose, hydroxypropyl cellulose (HPMC), 2-hydroxyethyl methacrylate, hydroxyethyl methacrylate (HEMA), polymethyl methacrylate (PMMA), sodium acrylate (SA), 2-acrylamide-2-methylpropanesulfonic acid (AMPS), polyvinyl alcohol, polyethylene oxide (PEO), polyethylene glycol, sodium carboxymethyl cellulose (CMC-Na), polyvinylpyrrolidone (PVP), methyl methacrylate, ethyl acrylate (EA), glycidyl methacrylate (GMA), sebacic acid, glutaraldehyde, genipin, glycerin, sorbitol, algae Salts, xanthan gum, agarose, carrageenan, gelatin, sodium alginate, hyaluronic acid, hyaluronic acid-polyethylene glycol-carboxylic acid (HA-PEG-COOH), methylcellulose, ethylcellulose (EC), sodium phosphorylated dextran, sodium carboxymethyl cellulose, polyanionic cellulose, acrylamide, polyacrylamide, starch, hydroxypropyl starch, chitosan, N,O-carboxymethyl chitosan, methacrylamide gelatin, hydroxyethyl methacrylate, N-vinylpyrrolidone (NVP), collagen, silk fibroin, soy protein isolate (SPI), laminin, RGD peptide, matrix glue, fibronectin, laminin-111 (LN-111), hyalin, Pristrom recombinant hyalin, lysine, lysine PEGylated derivatives, proteoglycans, protopeptides, fibroin glue, cyanoacrylate, etc. (2) Materials used for vascular simulation: flexible silicone, hydrogel, elastic bioresin, etc. with high elasticity and toughness; (3) Materials used for fat simulation: materials with low density and soft texture.

[0057] Step 3.2: Combination of multiple printing methods.

[0058] Specifically, based on the characteristics of different structures and materials, a combination of various printing methods is used to achieve the optimal printing effect. These printing methods include, but are not limited to: Photopolymerization (SLA / DLP / PolyJet, etc.): Suitable for high-precision detail printing, it can achieve fine layer printing of various photosensitive resin materials, especially suitable for the complex morphology of tumors and organ parenchyma; Fused Deposition Modeling (FDM): Suitable for printing support structures or large-volume components; Liquid silicone printing: Specifically designed for printing highly elastic silicone structures, such as blood vessels and flexible tissues; Sacrificial stent method: First, a soluble stent is printed as a temporary support for hollow structures such as blood vessels. After the main structure has solidified, the stent is dissolved and removed to form a precise cavity. Casting: Liquid material is injected into a pre-printed or manufactured mold, and then demolded after solidification. This method is suitable for specific materials or large-sized structures. Freeze-thaw cycle method: suitable for preparing hydrogel materials with porous structures, which can be used to simulate certain tissues or achieve specific tactile sensations.

[0059] By combining the above-mentioned printing methods, it is possible to accurately prepare tissues with different hardness, elasticity and density, such as blood vessels, tumors and fat.

[0060] In step S150, an initial biomimetic model is prepared using 3D printing technology based on the selected printing material and the biomechanical measurement results corresponding to each biological tissue. The initial biomimetic model is then post-processed and assembled to obtain a biomimetic tumor organ model.

[0061] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention includes the following steps in step S150: Step S151: Select multiple 3D printing technologies based on the biomechanical properties of the printing materials, and combine the selected multiple 3D printing technologies.

[0062] Step S152: Based on the printing material and the 3D modeling results, 3D printing is performed by combining multiple 3D printing technologies to obtain an initial biomimetic model.

[0063] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention further includes the following steps in step S150: Step S153: Based on the visual characteristics of each biological tissue in the 3D modeling results, the initial biomimetic model is painted and stained with color.

[0064] Step S154: Fill the cavities and tissue regions in the initial biomimetic model to obtain a biomimetic tumor organ model.

[0065] In some embodiments, the method for preparing a patient-specific multi-material biomimetic tumor organ model provided by the present invention further includes the following steps: Step S210: Based on the biomimetic tumor organ model, perform a flow test on the vascular network in the biomimetic tumor organ model to determine whether there is any blockage in the vascular lumen of the vascular network.

[0066] In step S220, simulated blood is filled into the blood vessel cavity using a liquid pump device. When the blood is flowing, it is determined that there is no blockage in the vascular network of the bionic tumor organ model. Otherwise, the location of the blockage in the blood vessel cavity is detected and the bionic tumor organ model is adjusted.

[0067] Combine Figure 2 As shown in the specific embodiment, the present invention provides a method for preparing a patient-specific multi-material biomimetic tumor organ model, step 4, post-processing and assembly. After 3D printing is completed, the model undergoes a series of post-processing and assembly steps to further improve the model's simulation accuracy and functionality. This includes the following steps: Step 4.1, color spraying and dyeing.

[0068] Specifically, the printed model undergoes detailed color spraying or dyeing to simulate the color, gloss, and blood supply of real organs and tissues. For example, tumor areas can be colored to match the color of real tumors, and blood vessels can be colored red or blue.

[0069] Step 4.2, biomimetic filling.

[0070] Specifically, depending on the needs, certain cavities or regions inside the model can be biomimetically filled, for example, by filling them with gels or liquids with specific biomechanical properties to simulate the feeling of fullness or liquid environment inside an organ.

[0071] Step 4.3, Vascular access testing and perfusion simulation.

[0072] Specifically, first, the printed vascular network undergoes a patency test to ensure that the vascular cavities are unobstructed. Second, simulated blood (such as red liquid) is filled into the vascular network, and a pump system simulates blood flow. During surgical procedures, when instruments touch or cut the blood vessels, simulated blood flows out, thus achieving controlled bleeding simulation and training surgeons to identify bleeding points and perform hemostasis.

[0073] Step 5, Scenario Application.

[0074] Includes the following steps: Step 5.1, Surgical training.

[0075] Specifically, it is applicable to practice in various minimally invasive tumor resection surgeries, including but not limited to complex surgeries such as liver cancer, kidney cancer, lung cancer, pancreatic cancer, stomach cancer, and colorectal cancer. Novice doctors can repeatedly practice core skills such as instrument operation, tissue separation, blood vessel management, and tumor boundary determination on high-fidelity models, significantly shortening the learning curve.

[0076] Step 5.2, Preoperative planning and rehearsal.

[0077] Specifically, personalized models are created for complex tumor cases in specific patients. Surgeons can rehearse surgical pathways, instrument selection, complication prediction, and high-risk procedures on a model that perfectly mirrors the patient's actual condition before surgery. This helps surgeons familiarize themselves with complex anatomical structures, optimize surgical plans, and significantly improve the success rate and safety of real-world surgeries.

[0078] In one embodiment, a patient-specific multi-material biomimetic tumor organ model is prepared by the above-described method for preparing a patient-specific multi-material biomimetic tumor organ model, the method comprising: Image segmentation technology is used to perform three-dimensional reconstruction based on medical image data in order to separate and model different anatomical structures within the patient's organs in three dimensions. Based on the results of 3D modeling, a correspondence between medical imaging data and different anatomical structures within the patient's organs is established to reconstruct the 3D information of the tumor. Biomechanical measurements were performed on each biological tissue in the gross specimen corresponding to the patient's organ to obtain the biomechanical measurement results of each biological tissue. Based on the biomechanical measurement results of various biological tissues, the 3D modeling results are structurally layered, and the multiple layered tissue regions are mapped with various printing materials that match the biomechanical properties in order to determine the printing materials. An initial biomimetic model was prepared using 3D printing technology based on the selected printing material and the biomechanical measurement results of each biological tissue. The initial biomimetic model was then post-processed and assembled to obtain a biomimetic tumor organ model.

[0079] The following examples, 1 and 2, further illustrate the patient-specific multi-material biomimetic tumor organ model and its preparation method provided by the present invention.

[0080] Example 1: This embodiment aims to prepare a patient-specific liver tumor model for minimally invasive surgery (MIS) training to simulate liver cancer lesions.

[0081] First, in the medical image acquisition and 3D modeling stage, enhanced abdominal CT images of a patient with a liver tumor were acquired. Then, the CT data was imported into professional 3D reconstruction software. Using methods such as threshold segmentation, region growing, and manual delineation, the liver parenchyma, liver tumor, hepatic hilar vessels (including the hepatic artery and portal vein), hepatic veins, and surrounding adipose tissue were precisely separated. Next, these separated structures were 3D reconstructed and calibrated to ensure that the relative positions and absolute dimensions of each structure were consistent with the patient's actual condition, laying the foundation for subsequent precise fabrication.

[0082] Secondly, in the tissue measurement and structural stratification design stage, fresh pig liver specimens were obtained, and the mechanical stiffness (e.g., Shore A stiffness) of the pig liver parenchyma, hepatic fibrous connective tissue, hepatic artery, and hepatic vein was measured using a stiffness tester. Simultaneously, mechanical data on human liver tumors in existing literature were referenced to determine the stiffness range of the simulated tumor. Based on the above measurement results and reference data, the digital model was divided into regions with different mechanical properties: the tumor region (set as high stiffness), the liver parenchyma region (set as medium stiffness, elasticity), the vascular region (set as high elasticity, toughness), and the fat region (set as low stiffness, softness). This meticulous stratification design aims to reproduce the physical properties of real organs to the greatest extent possible.

[0083] Subsequently, in the multi-material 3D printing stage, appropriate printing materials are selected based on the characteristics of different tissues. For tumor areas, a high-hardness photosensitive resin (e.g., dental resin, Shore D hardness approximately 80-90) is chosen, with a small amount of medical-grade brownish-red pigment added to simulate its appearance. For liver parenchyma areas, a medium-hardness and elastic photosensitive resin (e.g., flexible photosensitive resin, Shore A hardness approximately 40-50) is chosen, with a small amount of medical-grade hepatinum added. For vascular areas, a highly elastic liquid silicone (e.g., medical-grade transparent silicone, Shore A hardness approximately 5-10) is chosen, with small amounts of red pigment (simulating arteries) and blue pigment (simulating veins) added for differentiation. For fat areas, a low-density, soft transparent resin or a specific ratio of polyethylene glycol hydrogel is chosen, with a small amount of medical-grade yellow pigment added. This embodiment employs PolyJet multi-material 3D printing technology (e.g., Stratasys Connex series printers), which can simultaneously spray and cure multiple photosensitive resins in a single printing process, thereby achieving gradient changes and fine structures in the materials. For the vascular network, sacrificial support material can be first printed using PolyJet to form vascular channels. After the main structure is printed, the sacrificial material is dissolved and removed, thus forming a hollow vascular pathway. For the fatty region, it can be prepared using separate casting or filling methods. Ultimately, the printed model can accurately reproduce the overall morphology of the patient's liver, the location of the tumor, the direction of blood vessels, and the differences in mechanical properties between different tissues, providing a highly realistic entity for surgical training.

[0084] Finally, in the post-processing and assembly stage, the support material generated during printing is first removed using a high-pressure water gun or a special cleaning agent. Next, the model surface is locally sprayed to optimize the color and enhance the naturalness of color transitions; for example, a small amount of vascular texture is sprayed onto the tumor surface to increase realism. Then, vascular filling and patency testing are performed: red liquid (simulating arterial blood) and blue liquid (simulating venous blood) are injected into the printed vascular network using a pump system to test vascular patency and ensure that controlled "bleeding" effects are produced when blood vessels are cut during simulated surgery, thus providing a more realistic intraoperative experience. If the model is printed in modules, final precise positioning and assembly are performed to ensure that all components are tightly integrated to form a complete, functional liver tumor model.

[0085] Example 2: This embodiment aims to prepare a patient-specific colon tumor model for minimally invasive surgery (MIS) training to simulate colorectal cancer lesions.

[0086] First, during the medical image acquisition and 3D modeling phase, pelvic MRI images of a colorectal cancer patient were acquired. Then, specialized 3D reconstruction software was used to reconstruct the MRI data, precisely separating the colon wall, intraluminal tumor, extra-intestinal infiltrating tumor, mesenteric vessels, and surrounding adipose tissue. Through meticulous calibration, the relative positions and absolute dimensions of each structure were accurately restored, ensuring a high degree of consistency between the model and the patient's actual anatomy.

[0087] Secondly, in the tissue analysis and structural stratification design stage, fresh porcine colon specimens were obtained, and the stiffness and elasticity of the serosa, muscularis propria, and mucosa were measured using biomechanical testing instruments to understand the mechanical properties of each tissue layer. Simultaneously, referring to existing literature on the mechanical properties of human colon tumors, the stiffness range of the simulated tumor was determined. Based on the above measurement results and reference data, the digital model was divided into: the tumor region (set as high stiffness), the various layers of the colonic wall (set as layered stiffness and elasticity), the mesenteric vessels (set as high elasticity), and the adipose region (set as low stiffness). This stratified design aims to simulate the complex hierarchical structure of the colonic wall and the mechanical responses of different tissues.

[0088] Subsequently, in the multi-material 3D printing stage, appropriate printing materials are selected according to the layered design. The tumor area uses a high-hardness photosensitive resin with a small amount of gray-white pigment added to simulate its appearance. For each layer of the colon wall (including the mucosa, muscularis, and serosa), photosensitive resins or flexible silicone with different hardness and elasticity are selected for layered printing to simulate the layered structure and feel of the real intestinal wall. The vascular area uses highly elastic liquid silicone, with different colors used to simulate arteries and veins. The fat area uses low-density, soft, transparent resin or polyvinyl alcohol hydrogel, with added yellow pigment. This embodiment employs multi-nozzle 3D printing technology (e.g., a photopolymerization printer with multi-nozzle and multi-material compatibility) to achieve composite printing of different materials in a single printing process, thereby constructing a layered colon wall, tumor entity, and intricate vascular network. For the intestinal lumen structure, a sacrificial scaffold method or soluble core material technology can be combined, which is removed after printing to form a hollow intestinal lumen to simulate the real intestinal structure.

[0089] Finally, in the post-processing and assembly stage, the support material generated during printing is first removed. Next, the model surface is finely colored, especially at the junction of the tumor and normal intestinal wall, to enhance visual contrast and improve the model's realism. Then, vascular filling and access testing are performed: simulated blood is injected into the mesenteric vascular network, and its fluidity is tested to simulate potential bleeding during surgery. Finally, the printed parts are precisely positioned and assembled to form a complete, functional colon model with a tumor.

[0090] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0091] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for preparing a patient-specific multi-material biomimetic tumor organ model, characterized in that, The method comprises: Image segmentation technology is used to perform three-dimensional reconstruction based on medical image data in order to separate and model different anatomical structures within the patient's organs in three dimensions. Based on the 3D modeling results, a correspondence is established between the medical imaging data and different anatomical structures within the patient's organs to reconstruct the 3D information of the tumor. Biomechanical measurements were performed on each biological tissue in the gross specimen corresponding to the patient's organ to obtain the biomechanical measurement results of each biological tissue. Based on the biomechanical measurement results of each biological tissue, the three-dimensional modeling results are structurally layered, and the multiple layered tissue regions are mapped with a variety of printing materials that match the biomechanical properties in order to determine the printing materials. An initial biomimetic model was prepared using 3D printing technology based on selected printing materials and biomechanical measurement results corresponding to various biological tissues. The initial biomimetic model was then post-processed and assembled to obtain a biomimetic tumor organ model.

2. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 1, characterized in that, The medical imaging data are computed tomography (CT) scans and magnetic resonance imaging (MRI) images containing three-dimensional information of the patient's organs and tumor tissues. The three-dimensional information includes the tumor's boundaries, size, shape, location within the patient's organs, and the pathological relationship between the tumor and the surrounding vascular network and normal tissue.

3. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 1, characterized in that, The process of using image processing software to perform three-dimensional reconstruction based on medical image data to separate and model different anatomical structures within the patient's organs includes: The patient's medical imaging data is collected, and Mimics® software is used to separate different anatomical structures within the patient's organs based on the medical imaging data, thereby obtaining three-dimensional information of each anatomical structure within the patient's organs. Three-dimensional reconstruction is performed based on the three-dimensional information of various anatomical structures within the patient's organs to obtain the three-dimensional modeling results; The anatomical structures mentioned include the tumor solid, blood vessels, organ parenchyma, fat layer, and pathological features.

4. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 1, characterized in that, The biomechanical measurements of each biological tissue in the gross specimen corresponding to the patient's organ, to obtain the biomechanical measurement results of each biological tissue, include: Select gross specimens corresponding to the patient's organs, and use biomechanical measuring instruments to test the mechanical properties of each biological tissue in the gross specimens in order to determine the various test indicators in the biomechanical measurement results. The biological tissues mentioned include tumor tissue, organ parenchyma, blood vessel wall, adipose tissue, and connective tissue.

5. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 4, characterized in that, The biomechanical measurement results of each biological tissue are used to structurally layer the three-dimensional modeling results. Multiple layered tissue regions are then mapped to various printing materials with matching biomechanical properties to determine the printing materials, including: Based on the various test indicators in the biomechanical measurement results, the biomechanical characteristics of different biological tissues are determined, and the three-dimensional modeling results are structurally layered according to the biomechanical characteristics to obtain multiple tissue regions. The tissue region is composed of a tumor region, a healthy tissue region, a blood vessel region, and a fat region.

6. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 5, characterized in that, The method involves structurally stratifying the 3D modeling results based on biomechanical measurement results of various biological tissues, mapping the stratified tissue regions to multiple printing materials with matching biomechanical properties to determine the printing material, and further includes: Selected materials whose biomechanical properties match the biomechanical characteristics, as well as mixed materials combining multiple materials in proportion, are selected from the material library; Based on the biomechanical characteristics, different biological tissues are mapped to the candidate materials and hybrid materials to obtain the matching results between biological tissues and printing materials.

7. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 1, characterized in that, The process involves using 3D printing technology to prepare an initial biomimetic model based on selected printing materials and biomechanical measurement results corresponding to various biological tissues. The initial biomimetic model is then post-processed and assembled to obtain a biomimetic tumor organ model, including: Based on the biomechanical properties of the printing material, a variety of 3D printing technologies are selected and combined. Based on the printing material and the 3D modeling results, the initial biomimetic model is obtained by combining and applying the various 3D printing technologies.

8. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 7, characterized in that, The process involves using 3D printing technology to prepare an initial biomimetic model based on selected printing materials and biomechanical measurement results corresponding to various biological tissues, and then performing post-processing and assembly on the initial biomimetic model to obtain a biomimetic tumor organ model. The process also includes: Based on the visual characteristics of each biological tissue in the three-dimensional modeling results, the initial biomimetic model is painted and stained. The cavities and tissue regions in the initial biomimetic model are filled to obtain the biomimetic tumor organ model.

9. The method for preparing a patient-specific multi-material biomimetic tumor organ model according to claim 1, characterized in that, The method further comprises: Based on the biomimetic tumor organ model, a flow test is performed on the vascular network in the biomimetic tumor organ model to determine whether there is any blockage in the vascular cavities of the vascular network. Simulated blood is filled into the vascular cavity by a liquid pump device, and the vascular network in the bionic tumor organ model is determined to be free of blockage when the blood is flowing. Otherwise, the location of the blockage in the vascular cavity is detected and the bionic tumor organ model is adjusted.

10. A patient-specific multi-material biomimetic tumor organ model, characterized in that, The patient-specific multi-material biomimetic tumor organ model was prepared by the method described in any one of claims 1 to 9.

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