Construction method and system of Bouligand tissue engineering auricle

Abstract

The invention provides a method and a system for constructing a Bouligand tissue engineering auricle. The method for constructing the Bouligand tissue engineering auricle comprises the following steps: acquiring an auricle digital model; modeling by using the auricle digital model to obtain a nested auricle model; the nested auricle model is processed, and a Bouligand structure auricle model is obtained; and carrying out 3D printing on the auricle model with the Bouligand structure, so as to obtain the bionic tissue engineering auricle with the Bouligand structure. According to the technical scheme, the anisotropy of the natural auricle is simulated, so that the tissue engineering auricle capable of resisting stress and accurately maintaining the shape in vivo is obtained.

Description

Background Art

[0002] The integration of structure and function of tissue engineering auricle scaffold is of great significance for bionic natural auricle. Natural auricle cartilage mainly bears compressive stress and can undergo large deformation and return to its original shape, which is closely related to its special structure: the arrangement of collagen fibers is anisotropic due to the complex morphology of the auricle, which can extremely resist stress.

[0003] One of the representatives of anisotropic structures that can resist stress in nature is the Bouligand structure: in the exoskeleton of arthropods, chitin-protein fibrils are arranged in a spiral stack along their normal direction to form a planar layered structure, and adjacent fiber layers rotate at a constant angle to form a complete periodic arrangement of 180°, namely the Bouligand structure. The mantis shrimp's maxillopods can withstand thousands of high-speed impacts and have extremely excellent fracture toughness because of their Bouligand structure. The scales of the Arapaima are one of the hardest scales in the biological world because of their Bouligand structure, and can resist the attacks of piranhas. Summary of the invention

[0004] The present application provides a method and system for constructing a Bouligand tissue-engineered auricle, which is used to biomimetic the anisotropy of a natural auricle to obtain a tissue-engineered auricle that can resist stress and accurately maintain its shape in vivo.

[0005] In a first aspect, a method for constructing a Bouligand tissue engineering auricle is provided, comprising the following steps:

[0006] Obtain a digital model of the pinna;

[0007] Modeling is performed using the auricle digital model to obtain a nested auricle model;

[0008] Processing the nested auricle model to obtain a Bouligand structure auricle model;

[0009] The Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure.

[0010] In the above technical scheme, a digital model of the auricle is obtained; the digital model of the auricle is used for modeling to obtain a nested auricle model; the nested auricle model is processed to obtain a Bouligand structure auricle model; the Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure; and a tissue engineering auricle that can resist stress and accurately maintain its shape in vivo is obtained by biomimetic the anisotropy of the natural auricle.

[0011] In a specific implementation scheme, the step of obtaining the digital model of the auricle specifically includes:

[0012] The real human auricle is 3D scanned and preprocessed to obtain a 3D model of the human auricle.

[0013] The temporal bone part of the three-dimensional model of the human auricle is removed, and only the auricle part is retained to obtain the auricle digital model.

[0014] In a specific implementation scheme, the step of using the auricle digital model to perform modeling to obtain a nested auricle model specifically includes:

[0015] Modeling is performed using the auricle digital model to obtain an original auricle model;

[0016] Reserve a rim around the edge of the original auricle model;

[0017] The truss model is nested into the original auricle model by utilizing the hemming process to obtain the nested auricle model.

[0018] In a specific implementation scheme, the step of processing the nested auricle model to obtain the Bouligand structure auricle model specifically includes:

[0019] The nested auricle model is divided into corresponding slices by unit length, and then each adjacent layer is rotated clockwise by a set angle to obtain the Bouligand structure auricle model.

[0020] In a specific implementation scheme, the step of 3D printing the Bouligand structure auricle model to obtain a bionic tissue engineering auricle with a Bouligand structure specifically includes:

[0021] The Bouligand structure auricle model is sliced ​​and 3D printed using biological ink mixed with seed cells to obtain the bionic tissue engineering auricle with the Bouligand structure.

[0022] In a specific implementation scheme, the three-dimensional model of the human auricle is constructed by using one or more of CT scanning, laser scanning, and MRI scanning.

[0023] In a specific implementation scheme, the three-dimensional model of the human auricle is cut using one or more of Mimics Medical, CAD, Creo, Potato OSP, and Zbrush.

[0024] In a specific embodiment, the seed cells are one or more of chondrocytes, adipose stem cells, bone marrow stem cells, and mesenchymal stem cells.

[0025] In a specific embodiment, the bio-ink is one or more of methacrylate decellularized matrix, methacrylate gelatin, methacrylate hyaluronic acid, methacrylate sodium alginate, methacrylate silk protein, methacrylate chitosan, methacrylate chondroitin sulfate, and methacrylate elastin.

[0026] In a second aspect, a Bouligand tissue engineering auricle construction system is provided, comprising:

[0027] An auricle digital model module, used for obtaining an auricle digital model;

[0028] A nested auricle model module is used to perform modeling using the auricle digital model to obtain a nested auricle model;

[0029] A Bouligand structure auricle module, used for processing the nested auricle model to obtain a Bouligand structure auricle model;

[0030] The printing module is used to perform 3D printing on the Bouligand structure auricle model to obtain a bionic tissue engineering auricle with a Bouligand structure.

[0031] In the above technical scheme, a digital model of the auricle is obtained; the digital model of the auricle is used for modeling to obtain a nested auricle model; the nested auricle model is processed to obtain a Bouligand structure auricle model; the Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure; and a tissue engineering auricle that can resist stress and accurately maintain its shape in vivo is obtained by biomimetic the anisotropy of the natural auricle. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 A flowchart of the Bouligand tissue engineering auricle construction method provided in the embodiments of the present application;

[0033] Figure 2 This is a structural block diagram of the Bouligand tissue engineering auricle construction system provided in an embodiment of the present application. DETAILED DESCRIPTION

[0034] The present application is further described in detail below through the accompanying drawings and embodiments. Through these descriptions, the characteristics and advantages of the present application will become clearer and more specific.

[0035] The word "exemplary" is used exclusively herein to mean "serving as an example, embodiment, or illustration." Any embodiment described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments. Although various aspects of the embodiments are shown in the drawings, the drawings are not necessarily drawn to scale unless otherwise noted.

[0036] In addition, the technical features involved in different embodiments of the present application described below can be combined with each other as long as they do not conflict with each other.

[0037] To facilitate understanding of the Bouligand tissue engineering auricle construction method and system provided in the embodiments of the present application, its application scenario is first explained. The Bouligand tissue engineering auricle construction method and system provided in the embodiments of the present application are used to biomimetic the anisotropy of the natural auricle, and obtain a tissue engineering auricle that can resist stress and accurately maintain its shape in vivo. The integration of the structure and function of the tissue engineering auricle scaffold is of great significance for biomimetic natural auricle. The natural auricle cartilage mainly bears compressive stress, can be greatly deformed and restored to its original state, which is closely related to its special structure: the arrangement of collagen fibers is anisotropic due to the complex morphology of the auricle, which can resist stress very well. One of the representatives of anisotropic structures that can resist stress in nature is the Bouligand structure: in the exoskeleton of arthropods, chitin-protein fibrils are arranged in a spiral stacking manner along their normal direction to form a planar layered structure, and adjacent fiber layers are rotated at a constant angle to form a complete periodic arrangement of 180°, namely the Bouligand structure. The mantis shrimp's maxillopods can withstand thousands of high-speed impacts due to their Bouligand structure and have extremely excellent fracture toughness. The scales of the Arapaima are one of the hardest scales in the biological world due to their Bouligand structure and can resist the attacks of piranhas. For this reason, the present application embodiment provides a method and system for constructing a Bouligand tissue-engineered auricle to biomimetic the anisotropy of the natural auricle and obtain a tissue-engineered auricle that can resist stress and accurately maintain its shape in vivo. The following is a detailed description of the embodiment in conjunction with specific drawings.

[0038] refer to Figure 1 and Figure 2 , Figure 1 A flowchart of the Bouligand tissue engineering auricle construction method provided in the embodiments of the present application; Figure 2 This is a structural block diagram of the Bouligand tissue engineering auricle construction system provided in an embodiment of the present application.

[0039] exist Figure 1 In the present application, an embodiment provides a method for constructing a Bouligand tissue engineering auricle, comprising the following steps:

[0040] Obtain a digital model of the pinna;

[0041] Modeling is performed using the auricle digital model to obtain a nested auricle model;

[0042] Processing the nested auricle model to obtain a Bouligand structure auricle model;

[0043] The Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure.

[0044] In the above technical scheme, a digital model of the auricle is obtained; the digital model of the auricle is used for modeling to obtain a nested auricle model; the nested auricle model is processed to obtain a Bouligand structure auricle model; the Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure; and a tissue engineering auricle that can resist stress and accurately maintain its shape in vivo is obtained by biomimetic the anisotropy of the natural auricle.

[0045] In a specific implementation scheme, the step of obtaining the digital model of the auricle specifically includes:

[0046] The real human auricle is 3D scanned and preprocessed to obtain a 3D model of the human auricle.

[0047] The temporal bone part of the three-dimensional model of the human auricle is removed, and only the auricle part is retained to obtain the auricle digital model.

[0048] In a specific implementation scheme, the step of modeling using the auricle digital model to obtain a nested auricle model specifically includes:

[0049] Modeling is performed using the auricle digital model to obtain an original auricle model;

[0050] Reserve a rim around the edge of the original auricle model;

[0051] The truss model is nested into the original auricle model by utilizing the hemming process to obtain the nested auricle model.

[0052] In a specific implementation scheme, the step of processing the nested auricle model to obtain the Bouligand structure auricle model specifically includes:

[0053] The nested auricle model is divided into corresponding slices by unit length, and then each adjacent layer is rotated clockwise by a set angle to obtain the Bouligand structure auricle model.

[0054] In a specific implementation scheme, the step of 3D printing the Bouligand structure auricle model to obtain a bionic tissue engineering auricle with a Bouligand structure specifically includes:

[0055] The Bouligand structure auricle model is sliced ​​and 3D printed using biological ink mixed with seed cells to obtain the bionic tissue engineering auricle with the Bouligand structure.

[0056] In a specific implementation scheme, the three-dimensional model of the human auricle is constructed by using one or more of CT scanning, laser scanning, and MRI scanning.

[0057] In a specific implementation scheme, the three-dimensional model of the human auricle is cut using one or more of Mimics Medical, CAD, Creo, Potato OSP, and Zbrush.

[0058] In a specific embodiment, the seed cells are one or more of chondrocytes, adipose stem cells, bone marrow stem cells, and mesenchymal stem cells.

[0059] In a specific embodiment, the bio-ink is one or more of methacrylate decellularized matrix, methacrylate gelatin, methacrylate hyaluronic acid, methacrylate sodium alginate, methacrylate silk protein, methacrylate chitosan, methacrylate chondroitin sulfate, and methacrylate elastin.

[0060] Specifically, the Bouligand tissue engineering auricle construction method optimizes the tissue engineering auricle scaffold structure and constructs the Bouligand auricle structure by 3D printing, in order to obtain a tissue engineering auricle that can resist stress and accurately maintain its shape in vivo. The method includes the following steps:

[0061] (1) The real human auricle morphology was 3D scanned and processed by a CAD computer-aided design system, and then a mirrored 3D model of the human auricle was obtained using Boolean operations. The temporal bone part of the 3D model of the human auricle was removed using Mimics Medical 21.0 software, leaving only the auricle part, and the digital model of the auricle in STL format was exported.

[0062] (2) The digital model of the auricle was imported into SolidWorks 2023 software for modeling, and a 0.5-1 mm thick edging was reserved on the edge of the original auricle model, and its thickness was equal to the truss width. Subsequently, through design parameters, modular construction, and Boolean operations such as merging or adding and subtracting auricle and lattice modules, a truss model with a width of 0.5-2 mm, a spacing of 0.5-1 mm, and a thickness of 50-200 μm was embedded into the original auricle model.

[0063] (3) The nested model was highly divided into corresponding layers with a unit length of 50 to 200 μm. Each adjacent layer was then rotated clockwise (1° to 60°) so that the adjacent fiber layers were rotated at a constant angle to form a complete periodic arrangement of 180°. This gave the overall model a periodically rotating layer structure, thus obtaining the auricle model of the Bouligand structure. The model was imported into the PotatoOSP-Client V1.2.6 software, sliced ​​into layers of 50 to 200 μm, and uploaded to a 3D printer for printing.

[0064] (4) Adding bio-ink mixed with seed cells to the 3D printer, adjusting the light intensity, exposure time, base layer exposure time, and number of base layers to appropriate levels, and then printing, a bionic tissue engineering auricle with a Bouligand structure can be obtained.

[0065] Preferably, the three-dimensional digital model of the human auricle can be constructed using one or more of CT, laser scanning, MRI, etc.;

[0066] Preferably, the 3D model cutting software can use one or more of Mimics Medical, CAD, Creo, PotatoOSP, and Zbrush;

[0067] Preferably, the 3D bioprinter can be selected from one or more of projection light-curing printer, technical printing combined with suspension printing, and dynamic interface printing;

[0068] Preferably, the seed cells may be one or more of chondrocytes, adipose stem cells, bone marrow stem cells, mesenchymal stem cells and the like.

[0069] Preferably, the bio-ink can be a combination of one or more of methacrylate decellularized matrix, methacrylate gelatin, methacrylate hyaluronic acid, methacrylate sodium alginate, methacrylate silk protein, methacrylate chitosan, methacrylate chondroitin sulfate, and methacrylate elastin.

[0070] In this embodiment, the anisotropy of the natural auricle can be biomimetic, and its beneficial effects include:

[0071] (1) Effective load dispersion: The fiber and collagen arrangement of the auricular cartilage is anisotropic, and we use the Bouligand structure, which is also anisotropic, to imitate it. The Bouligand structure is a periodic rotating structure, which enables it to effectively disperse the load when the load stress is applied. This excellent performance is also perfectly maintained in the Bouligand structure we designed. In the finite element analysis, under the action of compression force, the maximum and minimum pressures of the Bouligand structure are alternately distributed in the form of stacked concentric circles, which gives it a filtering characteristic and can effectively buffer stress.

[0072] (2) Effectively limit local deformation: The Bouligand structure can also prevent the spread of structural fractures when subjected to stress, thereby limiting the local deformation of the structure. Finite element results show that under compression conditions, the contact area between the layers of the Bouligand structure increases, which also increases the friction between the layers, making it less likely to deform. At the same time, its comprehensive displacement and Z-axis displacement are small and are more evenly distributed in the stress area, which also confirms this characteristic.

[0073] (3) Uniform stress distribution: The excellent mechanical properties of the Bouligand structure are closely related to its layer deviation angle, that is, the smaller the rotation angle between each layer, the more conducive to the uniform distribution of stress. In this application, the layer deviation angle is set to 10° clockwise. The research results also confirmed that the Bouligand structure bioscaffold with a layer deviation angle of 10° has excellent mechanical properties in both in vitro and in vivo experiments. Not only is the compressive Young's modulus immediately after printing significantly higher than that of other groups, but also after 12 weeks of implantation in the body, its mechanical properties can reach the level of natural cartilage.

[0074] (4) Effectively promote cartilage regeneration: The mechanical strength of the biological scaffold after implantation in the body mainly depends on the tissue regeneration. In in vitro and in vivo experiments, the Bouligand structure has shown a good ability to promote cartilage proliferation, cartilage cell extracellular matrix secretion and cartilage tissue regeneration. This may be because the smaller layer deviation angle in the Bouligand structure makes the layers have a relatively continuous and gentle slope, which enables cells to grow upward in a "staircase" manner. This spatial directional distribution is also conducive to the Bouligand structure to maintain the morphology of the construct.

[0075] (5) Precise distribution of cells and materials: The integration of 3D bioprinting technology can achieve precise spatial distribution of cells and materials, which not only solves the problem of morphological control but also ensures the directional distribution of cells and materials.

[0076] In the above technical solution, the Bouligand structure refers to: in the exoskeleton of arthropods, chitin-protein fibrils are arranged in a spiral stacking manner along their normal direction to form a planar layered structure, and adjacent fiber layers are rotated at a constant angle to form a complete periodic arrangement of 180°. This structure has excellent impact resistance and fracture resistance. The present invention obtains the Bouligand tissue engineering auricle model by embedding a grid-like truss structure that rotates 10° clockwise layer by layer into a digital three-dimensional model of a real human ear, and can accurately prepare it through 3D printing. This model can significantly promote cartilage tissue regeneration in vivo and in vitro, and can resist stress and accurately maintain the shape of the auricle.

[0077] exist Figure 2 In the present application, an embodiment provides a Bouligand tissue engineering auricle construction system, comprising:

[0078] An auricle digital model module, used for obtaining an auricle digital model;

[0079] A nested auricle model module is used to perform modeling using the auricle digital model to obtain a nested auricle model;

[0080] A Bouligand structure auricle module, used for processing the nested auricle model to obtain a Bouligand structure auricle model;

[0081] The printing module is used to perform 3D printing on the Bouligand structure auricle model to obtain a bionic tissue engineering auricle with a Bouligand structure.

[0082] In the above technical scheme, a digital model of the auricle is obtained; the digital model of the auricle is used for modeling to obtain a nested auricle model; the nested auricle model is processed to obtain a Bouligand structure auricle model; the Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure; and a tissue engineering auricle that can resist stress and accurately maintain its shape in vivo is obtained by biomimetic the anisotropy of the natural auricle.

[0083] Those skilled in the art will appreciate that the present application may be implemented as a system, method or computer program product.

[0084] Therefore, the present disclosure may be specifically implemented in the following forms, namely: it may be completely hardware, it may be completely software (including firmware, resident software, microcode, etc.), or it may be a combination of hardware and software, generally referred to herein as a "circuit", "module" or "system". In addition, in some embodiments, the present application may also be implemented in the form of a computer program product in one or more computer-readable media, and the computer-readable medium may contain computer-readable program code.

[0085] Any combination of one or more computer-readable media can be used. Computer-readable media can be computer-readable signal media or computer-readable storage media. Computer-readable storage media can be, for example, but not limited to, electrical, magnetic, optical, electromagnetic, infrared, or semiconductor systems, devices or devices, or any combination of the above. More specific examples (non-exhaustive list) of computer-readable storage media include: electrical connections with one or more wires, portable computer disks, hard disks, random access memories (RAM), read-only memories (ROM), erasable programmable read-only memories (EPROM or flash memory), optical fibers, portable compact disk read-only memories (CD-ROM), optical storage devices, magnetic storage devices, or any suitable combination of the above. In this document, computer-readable storage media can be any tangible medium containing or storing a program, which can be used by an instruction execution system, device or device or used in combination with it.

[0086] Although the embodiments of the present application have been shown and described above, it is understood that the above embodiments are exemplary and cannot be understood as limiting the present application. A person of ordinary skill in the art can change, modify, replace and modify the above embodiments within the scope of the present application. On this basis, a variety of replacements and improvements can be made to the present application, all of which fall within the scope of protection of the present application.

Claims

1. A method for constructing a Bouligand tissue engineering auricle, characterized in that: The following steps are involved: Obtain a digital model of the pinna; Modeling is performed using the auricle digital model to obtain a nested auricle model; Processing the nested auricle model to obtain a Bouligand structure auricle model; The Bouligand structure auricle model is 3D printed to obtain a bionic tissue engineering auricle with a Bouligand structure.

2. The method for constructing Bouligand's tissue engineered auricle according to claim 1, characterized in that: The steps for obtaining a digital model of the auricle include: The real human auricle is 3D scanned and preprocessed to obtain a 3D model of the human auricle. The temporal bone part of the three-dimensional model of the human auricle is removed, and only the auricle part is retained to obtain the auricle digital model.

3. The method for constructing Bouligand's tissue engineered auricle according to claim 2, characterized in that: The step of modeling using the auricle digital model to obtain a nested auricle model specifically includes: Modeling is performed using the auricle digital model to obtain an original auricle model; Reserve a rim around the edge of the original auricle model; The truss model is nested into the original auricle model by utilizing the hemming process to obtain the nested auricle model.

4. The method for constructing Bouligand's tissue engineered auricle according to claim 3, characterized in that: The step of processing the nested auricle model to obtain a Bouligand structure auricle model specifically includes: The nested auricle model is divided into corresponding slices according to unit length in height, and then each adjacent layer is rotated clockwise at a set angle to obtain the Bouligand structure auricle model.

5. The method for constructing Bouligand's tissue engineered auricle according to claim 4, characterized in that: The step of 3D printing the Bouligand structure auricle model to obtain a bionic tissue engineering auricle with a Bouligand structure specifically includes: The Bouligand structure auricle model is sliced ​​and 3D printed using biological ink mixed with seed cells to obtain the bionic tissue engineering auricle with the Bouligand structure.

6. The method for constructing Bouligand's tissue engineered auricle according to claim 5, characterized in that: The three-dimensional model of the human auricle is constructed by using one or more of CT scanning, laser scanning, and MRI scanning.

7. The method for constructing Bouligand's tissue engineered auricle according to claim 6, characterized in that: The three-dimensional model of the human auricle is cut using one or more of Mimics Medical, CAD, Creo, PotatoOSP, and Zbrush.

8. The method for constructing Bouligand's tissue engineered auricle according to claim 7, characterized in that: The seed cells are one or more of chondrocytes, adipose stem cells, bone marrow stem cells, and mesenchymal stem cells.

9. The method for constructing Bouligand's tissue engineered auricle according to claim 8, characterized in that: The biological ink is one or more of methacrylate decellularized matrix, methacrylate gelatin, methacrylate hyaluronic acid, methacrylate sodium alginate, methacrylate silk protein, methacrylate chitosan, methacrylate chondroitin sulfate, and methacrylate elastin.

10. A Bouligand tissue engineering auricle construction system, characterized in that: include: An auricle digital model module, used for obtaining an auricle digital model; A nested auricle model module is used to perform modeling using the auricle digital model to obtain a nested auricle model; A Bouligand structure auricle module, used for processing the nested auricle model to obtain a Bouligand structure auricle model; The printing module is used to perform 3D printing on the Bouligand structure auricle model to obtain a bionic tissue engineering auricle with a Bouligand structure.

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