Skull repair stent with multi-layer structure, preparation method of skull repair stent and preparation process optimization method of skull repair stent

Abstract

The invention provides a multi-layer structure skull repair scaffold and a preparation method and a preparation process optimization method thereof, and relates to the technical field of skull repair scaffolds.The preparation method comprises the steps that CT and nuclear magnetic resonance scanning are carried out to obtain a defective skull tissue three-dimensional structure model; constructing a multi-layer structure skull repair scaffold structure reference model, wherein the multi-layer structure skull repair scaffold structure reference model comprises an external metal supporting layer, an internal biological ceramic degradation regeneration layer and a middle transition interface layer; the topological optimization is combined with extrusion simulation, printing simulation and sintering simulation for joint optimization; 3D printing slurry is prepared by adopting an extrusion 3D printing technology for printing to obtain a skull repair stent printing body with a multi-layer structure; and performing vacuum drying, vacuum sintering and cooling to obtain the skull repair stent with the multi-layer structure. Two materials of metal and ceramic are combined, and the outer-layer metal frame provides initial strength, rigidity and reliable fixing capacity required by an operation; the porous degradable biological ceramic on the inner layer creates a microenvironment beneficial to the generation of new bones, and finally the biodegradation of the scaffold and the in-situ regeneration of bone tissues are realized.

Description

Technical Field

[0001] This application relates to the field of cranioplasty technology, and more specifically, to multi-layered cranioplasty, its preparation method, and optimization of the preparation process. Background Technology

[0002] Currently, the widely used cranioplasty materials in clinical practice mainly fall into two categories: The first category consists of metallic materials (such as titanium alloys and tantalum metals). These materials possess excellent mechanical properties, enabling good initial fixation and mechanical support. However, as bioinert materials, they have poor integration with the host bone, easily leading to implant loosening. Their high elastic modulus may trigger a "stress shielding" effect, hindering the normal stress and remodeling of surrounding bone tissue. Furthermore, metallic implants cause severe artifact interference in CT and MRI imaging, affecting postoperative monitoring and posing risks of discomfort such as thermal conduction and cold sensations. The second category consists of biodegradable ceramic materials (such as hydroxyapatite, β-tricalcium phosphate, and their composites). These materials have good biocompatibility and osteoconductive / inductive activity, allowing for slow degradation by the body and guiding new bone ingrowth, ultimately achieving complete repair of bone defects. However, their inherent brittleness makes them unable to withstand surgical procedures and complex internal stresses, resulting in insufficient mechanical reliability, susceptibility to fracture, and difficulty in providing effective support for long-term, large-sized defects.

[0003] To simultaneously utilize the properties of metallic and ceramic materials, existing technologies employ the following methods: (1) Metal scaffold with ceramic material layer: A typical example of this approach is Chinese invention patent CN105797208A, which discloses a biodegradable metal implant for cranioplasty and its preparation method, including obtaining a biodegradable bio-coating through surface modification treatment of the implant mesh and bone screw holes. The biodegradable bio-coating is any one of calcium silicate, apatite, or tricalcium phosphate. A similar technical solution is Chinese invention patent CN101559240A, which discloses a cranioplasty material and its preparation method.

[0004] This type of solution enhances the biocompatibility of metal materials through ceramic material layers, but the main metal scaffold still suffers from a mismatch between its mechanical properties and those of the surrounding bone tissue.

[0005] (2) Ceramic support with attached metal material layer: A typical example of this solution is Chinese invention patent with publication number CN103201237A, which discloses an integral ceramic body with a mixed oxide edge region and a metallic surface. The ceramic body includes an oxide of a first metal, a mixed oxide edge region, and a metallic surface including metal on the mixed oxide edge region. The mixed oxide edge region includes an oxide of the first metal and an oxide of another metal with a high affinity for oxygen.

[0006] The aim of this approach is to provide better osseointegration through the metal material layer. However, when the ceramic scaffold as the main body is used as a cranial repair scaffold, it is difficult to provide sufficient fracture strength and achieve effective support for long-term, large-sized defects.

[0007] (3) Metal and ceramic hybrid materials: A typical example of this approach is Chinese invention patent CN105879122A, which discloses a biodegradable bioactive ceramic / metal composite material and its preparation method and application. This involves mixing and grinding biodegradable bioactive ceramic powder, biodegradable metal powder, and an additive solution to obtain a mixture, which is then sintered to obtain the biodegradable bioactive ceramic / metal composite material. A similar approach is Chinese invention patent CN107160534A, which describes a three-dimensional printed bioceramic composite scaffold and its application.

[0008] This type of solution offers superior absorption and degradation performance and initial mechanical properties, but the discontinuous ceramic and metal sintered structure poses a risk of support failure during the degradation and absorption process. Summary of the Invention

[0009] To address the aforementioned problems, the technical solution adopted in this application is an optimized method for the fabrication process of a multi-layered cranial repair scaffold, including: S1: Perform CT and MRI scans on the patient's skull defect to obtain a three-dimensional structural model of the defective skull tissue; S2: Based on the three-dimensional structural model of the defective skull tissue, a reference model of the multi-layered skull repair scaffold structure is constructed. The reference model of the multi-layered skull repair scaffold structure includes an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer. S3: Based on the structural benchmark model of the multilayered skull repair scaffold, the initial 3D printing path parameters are obtained by using the topology optimization method. Combined with extrusion simulation, printing simulation and sintering simulation, joint optimization is performed to establish the optimized material parameters, printing parameters and sintering parameters, and construct a parameterized model for printing the multilayered skull repair scaffold with material composition gradient changes and structural gradient changes. S4: Based on the parameterized model of the multi-layered skull repair scaffold obtained in step S3, the multi-layered skull repair scaffold is printed and manufactured using extrusion 3D printing technology; the 3D printing slurry for each layer is configured based on the material parameters optimized in step S3 and added to the material cylinder of the multi-nozzle printer; printing is performed based on the printing parameters optimized in step S3 to obtain the printed multi-layered skull repair scaffold. S5: Dry the multilayered skull repair scaffold printed body prepared in step S4 under vacuum conditions; S6: The multilayered skull repair scaffold printed body processed in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

[0010] Optionally, the intermediate transition interface layer includes at least three transition layers.

[0011] Optionally, Step S3, topology optimization, includes: Step S301: Based on the core functions of each structural layer, set differentiated optimization objectives and determine the optimization objective function; Step S302: Set constraint conditions with triple constraints of geometric constraints, mechanical constraints and process constraints; Step S303: Use finite element software to build a numerical model of the multi-layered support structure to provide a computational basis for topology optimization; Step S304: The SIMP algorithm is used for topology optimization. First, the overall topology is optimized, then the hierarchical local optimization is performed, and finally the discretized material distribution model is output. Then, the results are post-processed to finally convert the discretized material distribution model into specific path parameters for extrusion 3D printing. Step S3, the extrusion simulation, includes: Step S311: Establish a nozzle simulation model; Step S312: Slurry rheological test; Step S313: Fluid dynamics simulation; Step S314: Screening for optimal pulp components; Step S3, the printing simulation, includes: Step S321: Import data and build the print model; Step S322: Set variable parameters and simulation scenario; Step S323: Analyze the impact of parameters on printing results; Step S324: Optimize and determine the best printing parameters; Step S3 sintering simulation includes: Step S331: Prepare thermal expansion test sample and obtain parameters; Step S332: Import the printed structure and build the sintering model; Step S333: Simulate sintering shrinkage behavior; Step S334: Optimize the shape and size of the printed structure and establish a pre-compensation design for the initial printed model.

[0012] Optionally, it also includes a coupled loop correction of the results from extrusion simulation, printing simulation, and sintering simulation with topology optimization. The coupled loop correction includes topology optimization, a first loop, and a second loop, specifically including: First, topology optimization is performed by executing steps S301-S304 to obtain the initial slurry formulation. Then, the first loop is entered, and steps S311-S314 are executed to obtain the topology optimization correction constraints. Based on the topology optimization correction constraints, steps S301-S304 are repeated to obtain the corrected slurry formulation until the extrusion simulation coupling optimization is completed. Next, the second loop is entered, and steps S321-S324 and S331-S334 are executed sequentially to obtain the pre-compensation design correction topology optimization initial size of the initial printing model. Based on the corrected topology optimization initial size, steps S301-S304, S311-S314, S321-S324, and S331-S334 are repeated until the result coupling loop correction is completed.

[0013] This application also provides a method for preparing a multi-layered cranial repair scaffold, characterized in that: The method used is an optimized fabrication process for any of the aforementioned multi-layered cranial repair scaffolds, including: CT and MRI scans were performed on the patient's skull defect to obtain a three-dimensional structural model of the defective skull tissue. Based on the three-dimensional structural model of the defective skull tissue, a reference model of a multi-layered skull repair scaffold was constructed. The reference model of the multi-layered skull repair scaffold includes at least an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer. The multi-layered skull repair scaffold was printed using extrusion 3D printing technology. 3D printing slurry for each layer was prepared and added to the barrel of a multi-nozzle printer for printing to obtain the multi-layered skull repair scaffold print. The multi-layered skull repair scaffold print was dried under vacuum conditions and then vacuum sintered and cooled to obtain the multi-layered skull repair scaffold. The multi-layered skull repair scaffold includes at least an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer. The 3D printing slurry includes at least an outer metal support layer printing slurry, an inner bioceramic degradation and regeneration layer printing slurry, and an intermediate transition interface layer printing slurry.

[0014] Optionally, the printing paste for the external metal support layer, by weight, includes: 75-85 parts metal powder, 15-20 parts solvent, 1-5 parts binder, 1-5 parts rheology modifier, and 1-5 parts metal sintering aid. The printing paste for the internal bioceramic degradation and regeneration layer, by weight, includes: 60-70 parts ceramic powder, 1-5 parts binder, 30-40 parts solvent, 1-5 parts rheology modifier, and 1-5 parts ceramic sintering aid. The intermediate transition interface layer printing paste, by weight, includes: 20-70 parts of metal powder, 20-50 parts of ceramic powder, 1-5 parts of binder, 30-40 parts of solvent, 1-5 parts of rheology modifier, 1-5 parts of metal sintering aid, and 1-5 parts of ceramic sintering aid. Metal powder, ceramic powder, metal sintering aid, and ceramic sintering aid are all spherical particles with a particle size range of 1-50 μm.

[0015] Optionally, the metal powder is one or a mixture of several of titanium metal, titanium alloy, tantalum metal, tantalum alloy, nickel-titanium alloy, and cobalt alloy; the metal sintering aid is magnesium alloy; the binder is one or a mixture of several of sodium alginate and carboxymethyl cellulose; the solvent is one or a mixture of several of solvents such as water, ethanol, dichloromethane, and trichloromethane; the rheology modifier is one or a mixture of several of materials such as poloxamer, gelatin, acrylic acid, and polyacrylamide; the ceramic powder is one or a mixture of several of tricalcium phosphate, hydroxyapatite, calcium silicate, magnesium silicate, and manganese silicate; and the ceramic sintering aid is dicalcium phosphate.

[0016] Optionally, the drying process is carried out under vacuum conditions at a temperature of 40-80°C for 24 hours, with a vacuum degree of 10. 2 ~10 3 Pa.

[0017] Optionally, vacuum sintering includes the following steps: S601: In a hydrogen atmosphere, the temperature is increased from room temperature to 400℃ at a rate of 3-5℃ / min and held for 60min. S602: Under vacuum conditions, continue heating to 1200℃ at a rate of 8℃ / min, hold for 60min, and the absolute pressure corresponding to the vacuum degree is ≤10. -3 Pa; S603: Heat to 1200~1600℃ at 2℃ / min and hold for 120-480min; S604: Cool to 800°C at 10°C / min, then cool to room temperature in the furnace; S605: Heat to 700-800℃ at 10℃ / min, hold for 120-240min, and then cool to room temperature with the furnace.

[0018] This application also provides a multi-layered cranial repair scaffold, including an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer.

[0019] The beneficial effects of the multi-layered cranial repair scaffold, its preparation method, and the optimized preparation process provided in this application are as follows: (1) This application uses extrusion-based 3D printing technology to make a multilayered skull repair scaffold, uses finite element simulation technology to optimize the whole process of manufacturing of the multilayered skull repair scaffold, uses topology optimization method to optimize the structure design, uses extrusion simulation to design ink composition, uses printing simulation to design 3D printing process parameters, and uses sintering simulation to optimize the sintering process design, which greatly reduces the experimental workload and improves the design accuracy and production efficiency.

[0020] (2) This application aims to innovatively design and fabricate a "metal-ceramic multilayer and multi-layered cranial repair scaffold" by leveraging the technological advantages of extrusion 3D printing. This design cleverly combines the advantages of two materials: the outer layer is a dense metal framework, providing the initial strength, rigidity, and reliable fixation required for surgery, ensuring structural stability in the early stages of repair; the inner layer is a porous, biodegradable bioceramic, creating a microenvironment conducive to cell adhesion, blood vessel ingrowth, and new bone formation, ultimately achieving biodegradation of the scaffold and in-situ regeneration of bone tissue. This integrated structure, combining rigidity and flexibility with functional partitioning, is expected to overcome the shortcomings of single materials and represents a highly promising solution for achieving precise functional repair of the skull.

[0021] (3) In order to achieve a tight bond between the metal layer and the ceramic layer, an intermediate transition interface layer was developed. By adjusting the composition of the intermediate transition layer and optimizing the printing process parameters and sintering process parameters, a smooth transition from the ceramic layer to the intermediate transition interface layer to the metal layer was achieved, ensuring the high reliability of the cranial repair scaffold.

[0022] (4) Develop a precise sintering process using stepwise sintering assisted by low-temperature hydrogen sintering to precisely control the decomposition of organic matter and the fusion of metals. On the one hand, low-temperature hydrogen sintering removes residual oxygen from organic matter and other substances, ensuring the purity of the metal layer of the skull scaffold after sintering. At the same time, low-temperature hydrogen sintering can remove oxygen from the surface of metal particles, effectively improving the subsequent fusion performance of metal and ceramics. On the other hand, precise stepwise sintering can accurately control the sintering behavior, maximizing the improvement of uneven sintering between metal and ceramics, thereby improving the sintering quality. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0024] Figure 1 This is a flowchart of the optimized fabrication process of the multi-layered skull repair scaffold provided in the embodiments of this application; Figure 2 This is a flowchart illustrating the result coupling loop correction of the optimized fabrication process of the multi-layered skull repair scaffold provided in the embodiments of this application. Detailed Implementation

[0025] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and are not intended to limit the scope of this application.

[0026] This application provides a method for preparing a multi-layered skull repair scaffold, such as... Figure 1 As shown, it includes: S1: Perform CT and MRI scans on the patient's skull defect to obtain a three-dimensional structural model of the defective skull tissue; Simultaneously, CT and MRI scans were used to establish a three-dimensional structural model of the defective skull. The two scanning techniques complement each other in terms of bony structure characterization and soft tissue structure characterization, respectively, to establish an integrated three-dimensional model of the bone-soft tissue structure in the defective area.

[0027] CT scans, based on the attenuation difference imaging of X-rays penetrating tissues of different densities, offer high resolution for high-density bone tissue. They are used to extract geometric parameters of the bony boundaries, bone thickness, edge morphology, defect area, and volume of the skull defect, revealing details of bone hyperplasia, fracture lines, and residual bone fragments at the defect edges. MRI scans, based on proton magnetic resonance imaging, offer high resolution for low-density soft tissues, including brain tissue, dura mater, and subcutaneous fat. They are used to locate the compression and displacement of brain tissue beneath the defect area, the extent of edema, and the cerebrospinal fluid circulation pathway, avoiding secondary compression of brain tissue during scaffold design; they also differentiate the integrity of the dura mater, providing anatomical references for the design of the fit between the scaffold and the dura mater.

[0028] The scanning range covers the defect area and surrounding normal skull within a ≥2cm radius; the intracranial scanning range includes the brain tissue below the defect, cerebrospinal fluid cavities, and the intact scalp soft tissue covering the extracranial area. Data format is standardized after scanning, with the output format being DICOM 3.0. Patient positioning is consistent across both scanning techniques to ensure consistency between the anatomical coordinate systems of CT and MRI, reducing the difficulty of the registration process. Medical image processing software is used to read the DICOM files from CT and MRI, extracting pixel values, slice thickness, and FOV as metadata; the spatial coordinate systems of CT and MRI are unified based on the patient positioning information in the DICOM file.

[0029] Four types of structures—skull, brain tissue, dura mater, and scalp soft tissue—are extracted from two different modalities of data, providing independent data layers for subsequent fusion. Structure extraction can be performed using signal thresholding and manual adjustment. In practice, without involving deep learning, manually adjusting the boundary between the scalp and skull remains a common practice. This application does not involve any special improvements to the identification methods for these four types of structures, which are well-known to those skilled in the art.

[0030] After data extraction and segmentation, spatial registration is performed to align the data, mapping the soft tissue structures segmented by MRI and the skull structures segmented by CT to the same spatial coordinate system, ensuring the consistency of the anatomical positions of bone and soft tissue. Rigid registration is performed based on anatomical landmarks, adjusting only translation and rotation parameters without changing the structural geometry.

[0031] After registration and spatial alignment, data fusion and 3D modeling are performed. The registered skull data layer and soft tissue data layer are merged to generate an integrated 3D model. The bony structure is based on CT segmentation results, and MRI soft tissue data serves as spatial constraints. In the edge region of skull defects, a gradient smoothing algorithm is used to ensure a natural connection between the CT bone boundary and the MRI dura mater boundary, avoiding abrupt changes on the model surface.

[0032] Finally, surface reconstruction was performed, and isosurfaces of each structure were extracted from the fused data to generate a polygonal mesh model in STL format. Data such as defect area and volume, residual skull thickness, brain tissue displacement distance, and average thickness of scalp soft tissue were marked in the model for subsequent comparison.

[0033] S2: Based on the three-dimensional structural model of the defective skull tissue, a reference model of the multi-layered skull repair scaffold structure is constructed. The reference model of the multi-layered skull repair scaffold structure includes an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer.

[0034] Step S2, the multi-layered skull repair scaffold structure model, is designed based on CT and MRI data. The data is processed and imported into 3D design software to obtain a multi-layered skull repair scaffold structure model whose outer contour matches the 3D structural model of the defective skull tissue. This multi-layered skull repair scaffold structure model serves as the initialization data for the subsequent topology optimization in step S3, limiting the specific number of layers in the multi-layered skull repair scaffold and providing the initial thickness of each layer.

[0035] Examples 1-6 feature a five-layer structure, including an outer metal support layer, an inner bioceramic degradation and regeneration layer, and three intermediate transition interface layers. Example 7 features a three-layer structure, including an outer metal support layer, an inner bioceramic degradation and regeneration layer, and one intermediate transition interface layer. Comparative Example 1 features a two-layer structure, including an outer metal support layer and an inner bioceramic degradation and regeneration layer. The initial optimized baseline thickness of the multilayer structure is configured with equal thickness for each layer. For example, for the same 4.5mm thick skull location, in the initial model of the five-layer structure in Examples 1-6, the outer metal support layer and the inner bioceramic degradation and regeneration layer are each 1.5mm, and each intermediate transition interface layer is 0.5mm. In the initial model of the three-layer structure in Example 7, the outer metal support layer, the inner bioceramic degradation and regeneration layer, and the intermediate transition interface layer are each 1.5mm. In the initial model of the two-layer structure in Comparative Example 1, the outer metal support layer and the inner bioceramic degradation and regeneration layer are each 2.25mm.

[0036] S3: Based on the structural benchmark model of the multilayered skull repair scaffold, the initial 3D printing path parameters are obtained by using the topology optimization method. Combined with extrusion simulation, printing simulation and sintering simulation, joint optimization is performed to establish the optimized material parameters, printing parameters and sintering parameters, and construct a parameterized model for printing the multilayered skull repair scaffold with material composition gradient changes and structural gradient changes.

[0037] Step S3, topology optimization, includes: Step S301: Based on the core functions of each structural layer, set differentiated optimization objectives and determine the optimization objective function; the optimization objective for the core function of the external metal support layer is to maximize stiffness and minimize material usage; the optimization objective for the intermediate transition interface layer is to maximize interface bonding strength (the SIMP algorithm does not directly calculate the interface bonding strength value, but assigns the full-density elastic modulus of the external metal support layer, intermediate transition interface layer, and internal bioceramic degradation and regeneration layer to the corresponding layer units, performs overall density optimization based on the same design domain, and iteratively adjusts the density of each layer unit to ensure that the load is evenly distributed among the external metal support layer, intermediate transition interface layer, and internal bioceramic degradation and regeneration layer, avoiding stress peaks at the interface, thereby indirectly optimizing the interface bonding strength), minimize stress concentration, and balance stiffness and porosity; the optimization objective for the internal bioceramic degradation and regeneration layer is to maximize porosity while meeting the basic flexural strength requirements.

[0038] Step S302: Set constraint conditions with triple constraints of geometric constraints, mechanical constraints and process constraints; Geometric constraints are provided by a multi-layered skull repair scaffold structural model. The optimized thickness of each layer is not less than the design baseline value. In this embodiment, the design baseline value for the metal support layer is 1 mm, the design baseline value for the bioceramic degradation and regeneration layer is 1 mm, the total design baseline value for the intermediate transition interface layer is 1 mm, and the design baseline value for a single intermediate transition interface layer is 0.3 mm. Mechanical constraints are based on the physiological stress scenario of the skull, and boundary conditions are applied to ensure that the maximum stress of each layer does not exceed the material limit. Process constraints are adapted to the minimum formable features of extrusion 3D printing. The minimum solid structure size in the optimization results is constrained to be greater than or equal to the printer nozzle diameter, the minimum pore size is constrained to be greater than or equal to the printer nozzle control accuracy, and the pore diameter and pore connectivity are controlled to adapt to the bone ingrowth requirements. Step S303: Use finite element software to build a numerical model of the multilayer scaffold to provide a computational basis for topology optimization. First, import the multilayer cranial repair scaffold structure model (STL format) into the finite element analysis software, perform mesh generation and assign material properties. For the metal layer: use high-order solid elements (such as SOLID186) with a mesh size of 0.2-0.5mm to simulate stress concentration; for the ceramic layer: use porous media elements (such as PORO159) with a mesh size of 0.5-1mm to simulate pores; for the transition layer: use transition elements (such as SOLID185) to simulate the gradual change in mesh size to ensure interface mesh compatibility. Assign material properties according to the actual material parameters of each layer.

[0039] Step S304: The SIMP algorithm is used for topology optimization. First, the overall topology is optimized, then the hierarchical local optimization is performed, and finally the discretized material distribution model is output. Then, the results are post-processed to convert the discretized material distribution model into specific path parameters for extrusion 3D printing. By iteratively adjusting the material density of each unit (0 = no material, 1 = full material), the optimal material distribution cloud map is finally obtained, which includes information on whether each region of the optimal material distribution cloud map needs to be filled with material and the filling density.

[0040] Set a density penalty factor so that the material density ρ and elastic modulus E satisfy the following equation: E=E0×ρ p ; In the formula, E0 is the full-density elastic modulus of the material, and p is the density penalty factor, which penalizes the low-density region, prompting the optimization result to approach the 0 / 1 density, reducing the intermediate density region, and making it easier to convert the discretized material distribution model into a printing path.

[0041] Set the relative convergence error to ≤1e -3 When the difference between the objective functions of two iterations is less than the relative convergence error, optimization convergence is achieved to avoid over-iteration.

[0042] First, perform overall topology optimization to ensure that each layer is stressed in a coordinated manner. Then, perform layered local optimization, adjusting the support structure for the metal layer, the pore distribution for the ceramic layer, and the interface gradient for the transition layer, to avoid neglecting local details in the overall optimization.

[0043] The process iterates through applying load, calculating stress and strain, adjusting element density, and recalculating until the convergence criterion is met. The final output includes: a material density distribution cloud map, a stress cloud map of key regions, and a porosity report. The material density distribution cloud map represents full-density regions, no-density regions, and intermediate-density regions. The stress cloud map of key regions is used to verify whether the stress of each layer after optimization meets the constraints. The porosity report is used to determine whether the porosity of the ceramic layer meets the standard and whether the material content of the metal layer is optimal.

[0044] Then, post-processing is performed on the results. Thresholding is applied to the intermediate density region of the material density distribution cloud map output (in this embodiment, a density ≥ 0.7 is considered a filled region, and a density < 0.3 is considered a porous region) to generate a 0 / 1 discretized material distribution model. To remove isolated and excessively small structural features from the optimization results that do not meet the printing capabilities of the printing equipment, thus preventing the process from becoming unfeasible, in this embodiment, protrusions and depressions with a size <0.001mm are removed from the optimization results.

[0045] After post-processing, the topology optimization results are transformed into initial 3D printing path parameters, that is, the discretized material distribution model is transformed into specific path parameters for extrusion 3D printing. These specific path parameters include infill density, path type, layer thickness, and nozzle trajectory.

[0046] The material density obtained through topology optimization directly corresponds to the infill density in 3D printing. The material density obtained through topology optimization represents the actual infill status of the cells, i.e., whether infilling occurs. The infill density of the 3D printing area = the number of cells with a material density of 1 within the printing area / (printing area volume / cell volume). The path type is selected as material distribution morphology - path structure.

[0047] Based on the material distribution pattern of the optimization results, an appropriate extrusion 3D printing path type is selected. For the continuous dense area of ​​the outer metal support layer, a honeycomb path (Hexagonal) is selected. For the porous connected area of ​​the inner bioceramic degradation and regeneration layer, a grid path (Grid) or triangular path (Triangular) is selected. For the interface gradient area of ​​the intermediate transition layer, a gradient path is selected. From honeycomb to grid, the path direction is consistent with the principal stress direction in the optimization results to ensure that the topology optimization stiffness is consistent with the actual structural stiffness. (In this embodiment, the central axis of the multilayer skull repair scaffold structure model is used as the principal stress direction. When actually using the method provided in this application, it can be further adjusted according to the stress characteristics of the missing skull location.)

[0048] Layer thickness and nozzle parameters are determined based on the characteristic dimensions of the optimization results, primarily relying on the minimum structural wall thickness of the minimum pore diameter to determine the core parameters of the 3D printing layer thickness and nozzle: In this embodiment, a small layer thickness is selected in the complex feature areas of the internal bioceramic degradation and regeneration layer and the intermediate transition interface layer to ensure the accuracy of detail forming. The layer thickness at this location is 0.1-0.15 mm. In the simple and dense area of ​​the external metal support layer, a larger layer thickness is selected to improve printing efficiency. In this embodiment, the layer thickness at this location is 0.2-0.3 mm. The nozzle diameter matches the minimum feature size. In this embodiment, the nozzle diameter is 1 / 2 to 2 / 3 of the minimum feature size.

[0049] The extrusion speed and nozzle movement speed are matched inversely according to the filler density. In areas with high filler density, the extrusion speed is fast and the movement speed is slow, while in areas with low filler density, the extrusion speed is slow and the movement speed is fast.

[0050] Finally, the path is planned and the printing code is generated. The discretized material distribution model and the above parameters are imported into the 3D printing slicing software. The infill density, path type and layer thickness are set layer by layer. The software automatically generates the layered nozzle trajectory, including the path start / end point, path direction and filling order of each layer; process parameters such as nozzle temperature, platform temperature and extrusion speed; and path collision detection is performed to ensure that the nozzle does not collide with the printed structure.

[0051] In actual operation, the topology optimization process can be performed again based on the determined printing parameters. The determined printing parameters are then re-imported into the finite element software to establish a printing path-structural mechanics correlation model, simulate the stress of the printed bracket, and perform mechanical and process verification. Since this application performs extrusion simulation, printing simulation and sintering simulation after the topology optimization step, this verification step can be omitted.

[0052] Meanwhile, in the routine operation of this field, without performing extrusion simulation, printing simulation, and sintering simulation, it is necessary to conduct trial production for performance verification and process verification. Performance verification is used to determine whether the actual results meet the constraints. If the constraints are not met, the process returns to the topology optimization stage to adjust the material distribution. Process verification is used to determine whether the molding quality and dimensional accuracy can meet the requirements and whether there are any process problems. During trial production, the same slurry is used to conduct small-size trial printing. Molding quality mainly verifies whether there are broken wires, pore blockage, or interlayer separation. In terms of dimensional accuracy, it mainly verifies whether the dimensional deviation between the actual size and the design size is less than the allowable deviation threshold. For process problems, attention is paid to whether there is interface cracking.

[0053] Step S3, extrusion simulation, includes: The optimization goal of the extrusion simulation is to screen suitable slurry components for 3D printing (metal slurry, ceramic slurry, transition layer slurry), ensuring stable and uniform slurry flow during extrusion, and avoiding problems such as extrusion clogging and ink flow rate fluctuations caused by inappropriate components. The basic data used in the basic simulation comes from experimental tests, including the viscosity, shear rate, and yield stress of printing slurries with different component ratios.

[0054] Step S311: Establish a nozzle simulation model; using the fluid dynamics module of COMSOL software, construct a 1:1 three-dimensional model of the nozzle according to the actual size and structure of the 3D printer nozzle, clarify the geometric parameters of the nozzle inlet, internal channel and outlet, and simulate the flow path of the slurry in the nozzle.

[0055] Step S312: Slurry rheological test; For printing slurries with different component ratios (such as different combinations of metal powder content in the external metal support layer, different combinations of ceramic powder content in the internal bioceramic degradation and regeneration layer, and different ratios of metal powder and ceramic powder in the intermediate transition interface layer), conduct systematic rheological performance tests, record the slurry viscosity and yield stress at different shear rates as core data, and use them as the original input for fluid dynamics simulation.

[0056] Step S313: Fluid dynamics simulation; import the rheological data of each slurry ratio into the COMSOL nozzle model, and use the fluid dynamics simulation method to simulate the flow state of the slurry in the nozzle under different extrusion speeds, focusing on analyzing the stability of the ink flow rate and the uniformity of the slurry at the outlet.

[0057] Step S314: Screen the best slurry components; compare the simulation results of different slurry ratios, prioritize the slurry components with strong linear correlation between extrusion speed and ink flow rate, uniform outlet flow rate, and no obvious eddy or clogging risk, and determine the basic slurry formula for each layer.

[0058] To prevent the actual performance of the base slurry formulations for each layer obtained from the slurry optimization process in the extrusion simulation from not matching the performance benchmark of the topology optimization, the optimization range of each component in the slurry is limited to ±5% of the mass of each component before optimization in the extrusion simulation.

[0059] Extrusion simulation is used to adapt materials, ensure stable printing of the slurry, obtain the optimal slurry for printing, and deliver the rheological data of the slurry to the printing simulation stage.

[0060] Step S3, the printing simulation, includes: Step S321: Import data and build printing model; import the rheological data of the optimal slurry determined by extrusion simulation and the preliminary design model of the support obtained by topology optimization into ANSYS software, build the simulation environment of the printing process, and clarify the initial settings of the printing area and the nozzle movement trajectory.

[0061] Step S322: Set variable parameters and simulation scenario; design multiple parameter combinations with nozzle movement speed, extrusion speed, and printed layer thickness as core variables to simulate the printing process under different parameters. This step is based on the hardware parameters of the 3D printer, including nozzle movement range, nozzle movement speed, extrusion speed, and printing platform accuracy.

[0062] Step S323: Analyze the impact of parameters on printing results; monitor the consistency of filament diameter and the dimensional accuracy of the printed structure, and establish the correlation between parameters and printing results.

[0063] Step S324: Optimize and determine the best printing parameters; by comparing multiple sets of simulation results, select the parameter combination with the most uniform filament diameter and the highest structural dimensional accuracy, and finally determine the specific parameters for printing each layer.

[0064] Printing simulation optimizes printing parameters to ensure accurate printing during the printing process. These parameters are then sent to the sintering simulation stage to determine the optimal 3D printing process parameters. This ensures that the printed support structure has high dimensional accuracy and uniform filament diameter, avoiding problems such as poor interlayer bonding and structural deformation caused by improper parameters, and matching the geometric requirements of the designed multilayer structure.

[0065] Step S3 sintering simulation includes: Step S331: Prepare thermal expansion test samples and obtain parameters; according to the slurry formulation of each layer, prepare a cubic dense sample, and test the volume change from room temperature to the highest sintering temperature (1600℃) using a thermal expansion meter, extracting the coefficient of thermal expansion and shrinkage rate as core parameters. In this embodiment, the test sample is prepared by densely extruding the printing slurry into a 6mm×6mm×6mm cube.

[0066] Step S332: Import the printed structure and build the sintering model; import the ANSYS simulated printed support structure model into COMSOL software, assign the parameters obtained from the thermal expansion test to the corresponding layers, build a simulation environment for the sintering process, and simulate the temperature curve of vacuum sintering.

[0067] Step S333: Simulate sintering shrinkage behavior; focus on analyzing the overall shrinkage rate of the support during the sintering process and the local shrinkage differences of each layer, to determine whether there are interface stress concentration problems and overall structural deviation design contour problems caused by the shrinkage mismatch between the transition layer and the metal layer or ceramic layer.

[0068] Step S334: Optimize the shape and size of the printed structure and establish a pre-compensation design for the initial printed model. Based on the sintering simulation results, a pre-compensation design is performed on the initial printed model. For example, if the overall support shrinks by 5% after sintering, the overall size of the printed model is increased by 5.26%. If the shrinkage in a certain area is uneven, the printed structure in that area is adjusted to ensure that the size of the support after sintering accurately matches the defective skull model, while ensuring a tight interface bond without the risk of cracking. Uneven shrinkage is mainly caused by a mismatch in shrinkage rates. Adjusting the printed structure refers to uniformly increasing the local size of the material with a higher shrinkage rate based on the difference in shrinkage rates. As the simplest implementation method, the increase in local size is determined directly based on the material shrinkage rate ratio to prevent support structure failure due to shrinkage rate mismatch. This situation is mainly caused by different heat conduction rates during the sintering process and mainly occurs at the edges.

[0069] Sintering simulation is used to ensure that the sintered skull repair scaffold accurately matches the defect. It analyzes the shrinkage pattern of the scaffold during the sintering process, optimizes the initial shape and size of the printed structure, and offsets the error caused by sintering shrinkage. This ensures that the final size of the scaffold after sintering is completely matched with the three-dimensional model of the defective skull, while avoiding interface cracking or structural deformation caused by inconsistent shrinkage of each layer (metal, ceramic, and transition layer).

[0070] When adjusting the size configuration alone is insufficient to achieve interface matching between layers, the slurry configuration is adjusted based on the results of sintering simulation. This situation mainly occurs between layers with significant porosity differences.

[0071] like Figure 2 As shown, it also includes the coupling loop correction of the results from extrusion simulation, printing simulation, and sintering simulation with topology optimization. The result coupling loop correction includes topology optimization, the first loop, and the second loop, specifically including: First, topology optimization is performed by executing steps S301-S304 to obtain the initial slurry formulation. Then, the first loop is entered, and steps S311-S314 are executed to obtain the topology optimization correction constraints. Based on the topology optimization correction constraints, steps S301-S304 are repeated to obtain the corrected slurry formulation until the extrusion simulation coupling optimization is completed. Next, the second loop is entered, and steps S321-S324 and S331-S334 are executed sequentially to obtain the pre-compensation design correction topology optimization initial size of the initial printing model. Based on the corrected topology optimization initial size, steps S301-S304, S311-S314, S321-S324, and S331-S334 are repeated until the result coupling loop correction is completed.

[0072] Since extrusion simulation is used to control the printing performance of the slurry, and printing simulation and sintering simulation are used to control the precision of the finished product, the optimized slurry ratio is obtained by the first cycle of extrusion simulation and topology optimization, and the optimized printing parameters and sintering parameters are obtained by the second cycle of the entire process, which includes printing simulation and sintering simulation.

[0073] When the parameters obtained from the optimization steps of extrusion simulation, printing simulation, and sintering simulation cannot meet the optimization objectives of the subsequent steps, a result coupling loop correction is applicable. The goal of topology optimization is to optimize the printing structure based on the known material composition and target mechanical properties, and generate specific path parameters and printing codes for extrusion 3D printing. The goal of extrusion simulation is to optimize the slurry composition based on the flow properties of the extrusion slurry. The optimized slurry composition obtained from extrusion simulation will affect the final mechanical properties on the one hand, and on the other hand, there may be cases where the optimization still cannot meet the extrusion requirements.

[0074] To ensure the optimized slurry still meets usage requirements, it needs to be resubmitted to topology optimization to adjust the specific path parameters for 3D extrusion printing. If optimization still fails to meet extrusion requirements, the slurry composition needs to be reconfigured. Therefore, the first loop is required to complete the slurry optimization.

[0075] Sintering simulation, based on the specific path parameters of extrusion 3D printing obtained from topology optimization and the slurry configuration determined by the extrusion simulation, provides a pre-compensation design for the initial printing model. After the initial printing model undergoes pre-compensation design, the results of the topology simulation need to be revised based on this pre-compensation design, which in turn affects the printing simulation again, thus requiring a second cycle. Simultaneously, sintering simulation can determine the sintering effect of the transition layer, thereby reconfiguring the printing slurry and reducing the difference in interlayer thermal shrinkage performance. This process mainly affects the slurry configuration of the intermediate transition interface layer, especially when the intermediate transition interface layer includes multiple layers. Compared to simply and crudely grading the metal powder and ceramic powder layers (e.g., configuring the first transition layer near the inner bioceramic degradation and regeneration layer with 25 parts by weight of metal powder and 75 parts by weight of ceramic powder, the second transition layer with 50 parts by weight of metal powder and 50 parts by weight of ceramic powder, and the third transition layer with 75 parts by weight of metal powder and 25 parts by weight of ceramic powder, near the outer metal support layer), the slurry configuration optimized by sintering simulation has more realistic shrinkage performance.

[0076] S4: Based on the parameterized model of the multi-layered skull repair scaffold obtained in step S3, the multi-layered skull repair scaffold is printed and manufactured using extrusion 3D printing technology; the 3D printing slurry for each layer is configured based on the material parameters optimized in step S3 and added to the material cylinder of the multi-nozzle printer; printing is performed based on the printing parameters optimized in step S3 to obtain the printed multi-layered skull repair scaffold. S5: Dry the multilayered skull repair scaffold printed body prepared in step S4 under vacuum conditions; S6: The multilayered skull repair scaffold printed body processed in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

[0077] The 3D printing paste consists of an outer metal support layer printing paste, an inner bioceramic degradation and regeneration layer printing paste, and an intermediate transition interface layer printing paste.

[0078] The printing paste for the external metal support layer includes metal powder, binder, solvent, and rheology modifier; The printing paste for the internal bioceramic degradation and regeneration layer includes ceramic powder, binder, solvent, and rheology modifier; The intermediate transition interface layer printing paste includes metal powder, ceramic powder, binder, solvent, and rheology modifier.

[0079] The metal powder is titanium, the binder is sodium alginate, the solvent is water, the rheology modifier is poloxamer, and the ceramic powder is tricalcium phosphate.

[0080] The printing paste for the intermediate transition interface layer needs to be adjusted by controlling the composition of the metal powder to obtain suitable sintering shrinkage properties and ensure the interface bonding strength.

[0081] Metal powder, ceramic powder, metal sintering aid, and ceramic sintering aid are all spherical particles with a particle size range of 1-50 μm.

[0082] S5: Dry the multilayered skull repair scaffold prepared in step S4 under vacuum conditions; the vacuum degree is 10. 2 -10 3 Pa, temperature 40-80℃, time 24h.

[0083] S6: The multilayered skull repair scaffold obtained in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

[0084] Step S6, vacuum sintering, includes the following steps: S601: In a hydrogen atmosphere, the temperature is increased from room temperature to 400°C at a rate of 4°C / min and held for 60 minutes. S602: In a vacuum environment, continue heating to 1200℃ at a rate of 8℃ / min and hold for 60min; S603: Heat to 1200~1600℃ at 2℃ / min and hold for 120-480min; S604: Cool to 800°C at 10°C / min, then cool to room temperature in the furnace; S605: Heat to 700-800℃ at 10℃ / min, hold for 120-240min, and then cool to room temperature with the furnace.

[0085] Example 1 In this embodiment, the metal powder is titanium metal, the titanium metal grade is TA1 (according to standard GB / T 3620.1-2016 Titanium and Titanium Alloy Grades and Chemical Composition), the binder is sodium alginate, the solvent is water, the rheology modifier is poloxamer, the ceramic powder is tricalcium phosphate, the metal sintering aid is magnesium alloy, the magnesium alloy grade is WE43C (according to standard GB / T5153-2016 Wrought Magnesium and Magnesium Alloy Grades and Chemical Composition; the magnesium alloy composition in Examples 2-7 and Comparative Example 1 is exactly the same as in Example 1), and the ceramic sintering aid is dicalcium phosphate.

[0086] The printing paste composition of the external metal support layer is as follows: 75 parts by weight of titanium metal, 5 parts by weight of sodium alginate, 20 parts by weight of water, 5 parts by weight of poloxamer, and 5 parts by weight of magnesium alloy; in this application, "parts by weight" indicates the mass ratio between the components, and their total does not necessarily have to be 100 parts.

[0087] The composition of the printing paste for the internal bioceramic degradation and regeneration layer is as follows: 60 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, and 5 parts by weight of dicalcium phosphate. The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 70 parts by weight of titanium metal, 20 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. Second layer: 45 parts by weight of titanium metal, 35 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. The third layer (adjacent to the inner bioceramic degradation and regeneration layer): 20 parts by weight of titanium metal, 50 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0088] S5: Dry the multilayered cranial repair scaffold prepared in step S4 under vacuum conditions; the vacuum level is such that the corresponding absolute pressure is 10. 2 Pa, temperature 60℃, time 24h.

[0089] S6: The multilayered skull repair scaffold obtained in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

[0090] Step S6, vacuum sintering, includes the following steps: S601: In a hydrogen atmosphere, the temperature is increased from room temperature to 400°C at a rate of 4°C / min and held for 60 minutes. S602: Under vacuum conditions, the temperature is increased to 1200℃ at a rate of 8℃ / min and held for 60min. The absolute pressure corresponding to the vacuum level is 10. -3 P; S603: Continue to hold at 1200℃ for 120 minutes; S604: Cool to 800°C at 10°C / min, then cool to room temperature in the furnace; S605: Heat to 700℃ at 10℃ / min, hold for 120min, and then cool to room temperature with the furnace.

[0091] Example 2 The difference from Example 1 is that in this example, the metal powder is titanium alloy, the titanium alloy grade is TC4 (according to the standard GB / T 3620.1-2016 Titanium and Titanium Alloy Grades and Chemical Composition), the binder is carboxymethyl cellulose, the solvent is ethanol, the rheology modifier is gelatin, the ceramic powder is hydroxyapatite, the metal sintering aid is magnesium alloy, and the ceramic sintering aid is dicalcium phosphate.

[0092] The printing paste composition of the external metal support layer is as follows: 80 parts by weight of titanium alloy, 3 parts by weight of carboxymethyl cellulose, 15 parts by weight of ethanol, 3 parts by weight of gelatin, and 3 parts by weight of magnesium alloy. The composition of the printing paste for the internal bioceramic degradation and regeneration layer is as follows: 65 parts by weight of hydroxyapatite, 3 parts by weight of carboxymethyl cellulose, 35 parts by weight of ethanol, 3 parts by weight of gelatin, and 3 parts by weight of dicalcium phosphate. The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 70 parts by weight of titanium alloy, 20 parts by weight of hydroxyapatite, 3 parts by weight of carboxymethyl cellulose, 35 parts by weight of ethanol, 3 parts by weight of gelatin, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. Second layer: 45 parts by weight of titanium alloy, 35 parts by weight of hydroxyapatite, 3 parts by weight of carboxymethyl cellulose, 35 parts by weight of ethanol, 3 parts by weight of gelatin, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. The third layer (adjacent to the internal bioceramic degradation and regeneration layer): 20 parts by weight of titanium alloy, 50 parts by weight of hydroxyapatite, 3 parts by weight of carboxymethyl cellulose, 35 parts by weight of ethanol, 3 parts by weight of gelatin, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0093] S5: Dry the multilayered cranial repair scaffold prepared in step S4 under vacuum conditions; the vacuum level is such that the corresponding absolute pressure is 10.3 Pa, temperature 40℃, time 24h.

[0094] S6: The multilayered skull repair scaffold obtained in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

[0095] Step S6, vacuum sintering, includes the following steps: S601: In a hydrogen atmosphere, the temperature is increased from room temperature to 400°C at a rate of 3°C / min and held for 60 minutes. S602: Under vacuum conditions, the temperature is increased to 1200℃ at a rate of 8℃ / min and held for 60min. The absolute pressure corresponding to the vacuum level is 10. -3 P; S603: Heat to 1400℃ at a rate of 2℃ / min and hold for 300min; S604: Cool to 800°C at 10°C / min, then cool to room temperature in the furnace; S605: Heat to 750℃ at 10℃ / min, hold for 180min, and then cool to room temperature with the furnace.

[0096] Example 3 The difference from Example 1 is that in this example, the metal powder is tantalum metal, the tantalum metal grade is Ta1 (according to standard YS / T751-2011 Tantalum and Tantalum Alloy Grades and Chemical Composition), the binder is sodium alginate, the solvent is dichloromethane, the rheology modifier is acrylic acid, the ceramic powder is calcium silicate, the metal sintering aid is magnesium alloy, and the ceramic sintering aid is dicalcium phosphate.

[0097] The printing paste composition of the external metal support layer is as follows: 85 parts by weight of tantalum metal, 1 part by weight of sodium alginate, 20 parts by weight of dichloromethane, 1 part by weight of acrylic acid, and 1 part by weight of magnesium alloy. The composition of the printing paste for the internal bioceramic degradation and regeneration layer is as follows: 70 parts by weight of calcium silicate, 1 part by weight of sodium alginate, 30 parts by weight of dichloromethane, 1 part by weight of acrylic acid, and 1 part by weight of dicalcium phosphate. The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 70 parts by weight of tantalum metal, 20 parts by weight of calcium silicate, 1 part by weight of sodium alginate, 30 parts by weight of dichloromethane, 1 part by weight of acrylic acid, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. Second layer: 45 parts by weight of tantalum metal, 35 parts by weight of calcium silicate, 1 part by weight of sodium alginate, 30 parts by weight of dichloromethane, 1 part by weight of acrylic acid, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. The third layer (adjacent to the inner bioceramic degradation and regeneration layer): 20 parts by weight of tantalum metal, 50 parts by weight of calcium silicate, 1 part by weight of sodium alginate, 30 parts by weight of dichloromethane, 1 part by weight of acrylic acid, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0098] S5: Dry the multilayered cranial repair scaffold prepared in step S4 under vacuum conditions; the vacuum level is such that the corresponding absolute pressure is 10. 2 Pa, temperature 80℃, time 24h.

[0099] S6: The multilayered skull repair scaffold obtained in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

[0100] Step S6, vacuum sintering, includes the following steps: S601: In a hydrogen atmosphere, the temperature is increased from room temperature to 400°C at a rate of 5°C / min and held for 60 minutes. S602: Under vacuum conditions, the temperature is increased to 1200℃ at a rate of 8℃ / min and held for 60min. The absolute pressure corresponding to the vacuum level is 10. -3 P; S603: Heat to 1600℃ at a rate of 2℃ / min and hold for 480min; S604: Cool to 800°C at 10°C / min, then cool to room temperature in the furnace; S605: Heat to 800℃ at 10℃ / min, hold for 240min, and then cool to room temperature with the furnace.

[0101] Example 4 The difference from Example 1 is that in this example, the metal powder is tantalum alloy, the tantalum alloy grade is TaW10 (according to standard YS / T751-2011 Tantalum and Tantalum Alloy Grades and Chemical Composition), the binder is sodium alginate, the solvent is chloroform, the rheology modifier is polyacrylamide, the ceramic powder is magnesium silicate, the metal sintering aid is magnesium alloy, and the ceramic sintering aid is dicalcium phosphate.

[0102] The printing paste composition of the external metal support layer is as follows: 75 parts by weight of tantalum alloy, 5 parts by weight of sodium alginate, 20 parts by weight of chloroform, 5 parts by weight of polyacrylamide, and 5 parts by weight of magnesium alloy. The composition of the printing paste for the internal bioceramic degradation and regeneration layer is as follows: 60 parts by weight of magnesium silicate, 5 parts by weight of sodium alginate, 40 parts by weight of chloroform, 5 parts by weight of polyacrylamide, and 5 parts by weight of dicalcium phosphate. The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 70 parts by weight of tantalum alloy, 20 parts by weight of magnesium silicate, 5 parts by weight of sodium alginate, 40 parts by weight of chloroform, 5 parts by weight of polyacrylamide, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. Second layer: 45 parts by weight of tantalum alloy, 35 parts by weight of magnesium silicate, 5 parts by weight of sodium alginate, 40 parts by weight of chloroform, 5 parts by weight of polyacrylamide, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. The third layer (adjacent to the inner bioceramic degradation and regeneration layer): 20 parts by weight of tantalum alloy, 50 parts by weight of magnesium silicate, 5 parts by weight of sodium alginate, 40 parts by weight of chloroform, 5 parts by weight of polyacrylamide, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0103] This embodiment is completely identical to Embodiment 1 in steps S5 and S6.

[0104] Example 5 The difference from Example 1 is that in this example, the metal powder is a nickel-titanium alloy (composed of 56% Ni and 44% Ti, conforming to GB / T 24627-2023 Nickel-titanium shape memory alloy for surgical implants), the binder is sodium alginate, the solvent is water, the rheology modifier is poloxamer, the ceramic powder is manganese silicate, the metal sintering aid is magnesium alloy, and the ceramic sintering aid is dicalcium phosphate.

[0105] The printing paste composition of the external metal support layer is as follows: 75 parts by weight of nickel-titanium alloy, 5 parts by weight of sodium alginate, 20 parts by weight of water, 5 parts by weight of poloxamer, and 5 parts by weight of magnesium alloy. The printing paste for the internal bioceramic degradation and regeneration layer consists of: 60 parts by weight of manganese silicate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, and 5 parts by weight of dicalcium phosphate. The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 70 parts by weight of nickel-titanium alloy, 20 parts by weight of manganese silicate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. Second layer: 45 parts by weight of nickel-titanium alloy, 35 parts by weight of manganese silicate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. The third layer (adjacent to the inner bioceramic degradation and regeneration layer): 20 parts by weight of nickel-titanium alloy, 50 parts by weight of manganese silicate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0106] This embodiment is completely identical to Embodiment 1 in steps S5 and S6.

[0107] Example 6 The difference from Example 1 is that in this example, the metal powder is a cobalt alloy (composed of 27% Cr, 5% Mo, 67% Co, with the remaining elements conforming to the requirements of GB 17100-1997 Cast cobalt-chromium-molybdenum alloy for surgical implants), the binder is sodium alginate, the solvent is water, the rheology modifier is poloxamer, the ceramic powder is tricalcium phosphate, the metal sintering aid is magnesium alloy, and the ceramic sintering aid is dicalcium phosphate.

[0108] The printing paste composition of the external metal support layer is as follows: 75 parts by weight of cobalt alloy, 5 parts by weight of sodium alginate, 20 parts by weight of water, 5 parts by weight of poloxamer, and 5 parts by weight of magnesium alloy. The composition of the printing paste for the internal bioceramic degradation and regeneration layer is as follows: 60 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, and 5 parts by weight of dicalcium phosphate. The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 70 parts by weight of cobalt alloy, 20 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. Second layer: 45 parts by weight of cobalt alloy, 35 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate. The third layer (adjacent to the inner bioceramic degradation and regeneration layer): 20 parts by weight of cobalt alloy, 50 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0109] This embodiment is completely identical to Embodiment 1 in steps S5 and S6.

[0110] Example 7 In this embodiment, the composition of the printing paste for the outer metal support layer and the printing paste for the inner bioceramic degradation and regeneration layer are completely identical to those in Example 1. The difference between this embodiment and Example 1 is that it includes only one intermediate transition interface layer.

[0111] The composition of the printing paste for the intermediate transition interface layer is as follows: First layer (adjacent to the outer metal support layer): 50 parts by weight of titanium metal, 35 parts by weight of tricalcium phosphate, 5 parts by weight of sodium alginate, 40 parts by weight of water, 5 parts by weight of poloxamer, 2.5 parts by weight of magnesium alloy, and 2.5 parts by weight of dicalcium phosphate.

[0112] This embodiment is completely identical to Embodiment 1 in steps S5 and S6.

[0113] Comparative Example 1 The composition of the printing paste for the outer metal support layer and the inner bioceramic degradation and regeneration layer in this comparative example are completely identical to those in Example 1. The difference between this comparative example and Example 1 is that it does not include an intermediate transition interface layer.

[0114] This comparative example is completely consistent with Example 1 in steps S5 and S6.

[0115] The composition of the printing paste for the external metal support layer in Examples 1-7 and Comparative Example 1 is shown in Table 1: Table 1. Composition of printing paste for the external metal support layer in Examples 1-7 and Comparative Example 1

[0116] The composition of the printing paste for the internal bioceramic degradation and regeneration layer in Examples 1-7 and Comparative Example 1 is shown in Table 2: Table 2. Composition of printing paste for the internal bioceramic degradation and regeneration layer in Examples 1-7 and Comparative Example 1

[0117] The composition of the printing paste for the intermediate transition interface layer in Examples 1-7 and Comparative Example 1 is shown in Table 3: Table 3. Composition of printing paste for the intermediate transition interface layer in Examples 1-7 and Comparative Example 1

[0118] In Table 3, the proportions of each intermediate transition interface layer corresponding to Examples 1-6 are arranged from top to bottom according to the order from the outer metal support layer to the inner bioceramic degradation and regeneration layer.

[0119] The differences in process parameters between Examples 1-7 and Comparative Example 1 are shown in Table 4: Table 4. Differences in process parameters between Examples 1-7 and Comparative Example 1

[0120] The performance test results of Examples 1-7 and Comparative Example 1 are statistically summarized in Table 5: Table 5. Statistical analysis of performance test results for Examples 1-7 and Comparative Example 1

[0121] The interface bonding strength test was conducted in accordance with GB / T 44990-2024 Test Method for Interface Bonding Strength of Laser Cladding Repair Layer.

[0122] The interfacial shrinkage rate test was conducted according to "QB / T 1548-2015 Method for Determination of Linear Shrinkage Rate of Ceramic Green Body Clay". During the test, the sample after vacuum drying (i.e., the sample that has completed step S5) was taken, and the length of the interfacial position was measured as L1. The sample was then vacuum sintered according to the process S6 of each embodiment, and the radial length of the interfacial position of the vacuum sintered sample was measured as L2. The firing linear shrinkage rate Y2 was calculated as the single interfacial shrinkage rate based on the following formula: ; The single-interface shrinkage rate of each sample at all interface locations is measured using the above method, and the average value is taken as the interfacial shrinkage rate of the sample.

[0123] Porosity testing was conducted in accordance with GB / T21650.1-2008 / 1S0 15901-1:2005 Determination of pore size distribution and porosity of solid materials by mercury porosimetry and gas adsorption method - Part 1: Mercury porosimetry.

[0124] As can be seen from Table 5, the interfacial tensile strength of Examples 1-6, which use three intermediate transition interface layers, is generally better than that of Example 7, while the interfacial shrinkage rate of Examples 1-6 is lower than that of Example 7; while the interfacial tensile strength of Example 7, which uses one intermediate transition interface layer, is better than that of Comparative Example 1, which does not use an intermediate transition interface layer, while the interfacial shrinkage rate of Example 7 is lower than that of Comparative Example 1.

[0125] The above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application, and should all be included within the protection scope of this application.

Claims

1. An optimized method for fabricating a multi-layered skull repair scaffold, characterized in that, include: S1: Perform CT and MRI scans on the patient's skull defect to obtain a three-dimensional structural model of the defective skull tissue; S2: Based on the three-dimensional structural model of the defective skull tissue, construct a reference model of a multi-layered skull repair scaffold structure. The reference model of the multi-layered skull repair scaffold structure includes an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer. S3: Based on the reference model of the multilayered skull repair scaffold structure, the initial 3D printing path parameters are obtained by the topology optimization method. Combined with extrusion simulation, printing simulation and sintering simulation, joint optimization is performed to establish the optimized material parameters, printing parameters and sintering parameters, and construct a parameterized model for printing the multilayered skull repair scaffold with material composition gradient change and structural gradient change. S4: Based on the parameterized model of the multi-layered cranioplasty obtained in step S3, the multi-layered cranioplasty is printed and manufactured using extrusion 3D printing technology; the 3D printing slurry for each layer is configured based on the optimized material parameters in step S3 and added to the barrel of the multi-nozzle printer respectively. Printing is performed based on the optimized printing parameters in step S3 to obtain a multi-layered skull repair scaffold print. S5: Dry the multilayered skull repair scaffold printed body prepared in step S4 under vacuum conditions; S6: The multilayered skull repair scaffold printed body processed in step S5 is subjected to vacuum sintering and cooled to obtain the multilayered skull repair scaffold.

2. The optimized method for fabricating a multi-layered cranial repair scaffold according to claim 1, characterized in that: The intermediate transition interface layer includes at least three transition layers.

3. The optimized method for fabricating a multi-layered cranial repair scaffold according to claim 1 or 2, characterized in that: The topology optimization in step S3 includes: Step S301: Based on the core functions of each structural layer, set differentiated optimization objectives and determine the optimization objective function; Step S302: Set constraint conditions with triple constraints of geometric constraints, mechanical constraints and process constraints; Step S303: Use finite element software to build a numerical model of the multi-layered support structure to provide a computational basis for topology optimization; Step S304: The SIMP algorithm is used for topology optimization. First, the overall topology is optimized, then the hierarchical local optimization is performed, and finally the discretized material distribution model is output. Then, the results are post-processed to finally convert the discretized material distribution model into specific path parameters for extrusion 3D printing. The extrusion simulation in step S3 includes: Step S311: Establish a nozzle simulation model; Step S312: Slurry rheological test; Step S313: Fluid dynamics simulation; Step S314: Screening for optimal pulp components; Step S3, the printing simulation, includes: Step S321: Import data and build the print model; Step S322: Set variable parameters and simulation scenario; Step S323: Analyze the impact of parameters on printing results; Step S324: Optimize and determine the best printing parameters; The sintering simulation in step S3 includes: Step S331: Prepare thermal expansion test sample and obtain parameters; Step S332: Import the printed structure and build the sintering model; Step S333: Simulate sintering shrinkage behavior; Step S334: Optimize the shape and size of the printed structure and establish a pre-compensation design for the initial printed model.

4. The optimized method for fabricating a multi-layered cranial repair scaffold according to claim 3, characterized in that: It also includes a coupled loop correction of the results from extrusion simulation, printing simulation, and sintering simulation with topology optimization. This coupled loop correction includes topology optimization, a first loop, and a second loop, specifically including: First, topology optimization is performed by executing steps S301-S304 to obtain the initial slurry formulation. Then, the first loop is entered, and steps S311-S314 are executed to obtain the topology optimization correction constraints. Based on the topology optimization correction constraints, steps S301-S304 are repeated to obtain the corrected slurry formulation until the extrusion simulation coupling optimization is completed. Next, the second loop is entered, and steps S321-S324 and S331-S334 are executed sequentially to obtain the pre-compensation design correction topology optimization initial size of the initial printing model. Based on the corrected topology optimization initial size, steps S301-S304, S311-S314, S321-S324, and S331-S334 are repeated until the result coupling loop correction is completed.

5. A method for preparing a multi-layered cranial repair scaffold, characterized in that: The method for optimizing the fabrication process of a multi-layered cranial repair scaffold as described in any one of claims 1-4 is used, including: CT and MRI scans were performed on the patient's skull defect to obtain a three-dimensional structural model of the defective skull tissue. Based on this model, a reference model for a multi-layered skull repair scaffold was constructed. This reference model includes at least an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer. The multi-layered skull repair scaffold was manufactured using extrusion 3D printing technology. 3D printing slurries for each layer were prepared and added to the barrel of a multi-nozzle printer for printing, resulting in a printed multi-layered skull repair scaffold. The printed multi-layered skull repair scaffold was dried under vacuum conditions and then vacuum sintered and cooled to obtain the final multi-layered skull repair scaffold. The multi-layered skull repair scaffold includes at least an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer. The 3D printing slurry includes at least an outer metal support layer printing slurry, an inner bioceramic degradation and regeneration layer printing slurry, and an intermediate transition interface layer printing slurry.

6. The method for preparing a multi-layered cranial repair scaffold according to claim 5, characterized in that: The printing paste for the external metal support layer, by weight, includes: 75-85 parts metal powder, 15-20 parts solvent, 1-5 parts binder, 1-5 parts rheology modifier, and 1-5 parts metal sintering aid. The printing paste for the internal bioceramic degradation and regeneration layer comprises, by weight: 60-70 parts ceramic powder, 1-5 parts binder, 30-40 parts solvent, 1-5 parts rheology modifier, and 1-5 parts ceramic sintering aid. The intermediate transition interface layer printing paste, by weight, includes: 20-70 parts of metal powder, 20-50 parts of ceramic powder, 1-5 parts of binder, 30-40 parts of solvent, 1-5 parts of rheology modifier, 1-5 parts of metal sintering aid, and 1-5 parts of ceramic sintering aid. The metal powder, ceramic powder, metal sintering aid, and ceramic sintering aid are all spherical particles with a particle size range of 1-50 μm.

7. The method for preparing a multi-layered cranial repair scaffold according to claim 6, characterized in that: The metal powder is one or a mixture of several of titanium metal, titanium alloy, tantalum metal, tantalum alloy, nickel-titanium alloy, and cobalt alloy; the metal sintering aid is magnesium alloy; the binder is one or a mixture of several of sodium alginate and carboxymethyl cellulose; the solvent is one or a mixture of several of solvents such as water, ethanol, dichloromethane, and trichloromethane; the rheology modifier is one or a mixture of several of materials such as poloxamer, gelatin, acrylic acid, and polyacrylamide; the ceramic powder is one or a mixture of several of tricalcium phosphate, hydroxyapatite, calcium silicate, magnesium silicate, and manganese silicate; and the ceramic sintering aid is dicalcium phosphate.

8. The method for preparing a multi-layered cranial repair scaffold according to claim 5, characterized in that: The drying process under vacuum conditions involves a temperature of 40-80°C, a time of 24 hours, and a vacuum degree of 10. 2 ~10 3 Pa.

9. The method for preparing a multi-layered cranial repair scaffold according to claim 5, characterized in that: The vacuum sintering includes the following steps: S601: In a hydrogen atmosphere, the temperature is increased from room temperature to 400℃ at a rate of 3-5℃ / min and held for 60min. S602: Under vacuum conditions, continue heating to 1200℃ at a rate of 8℃ / min, hold for 60min, and the absolute pressure corresponding to the vacuum degree is ≤10. -3 Pa; S603: Heat to 1200~1600℃ at 2℃ / min and hold for 120-480min; S604: Cool to 800°C at 10°C / min, then cool to room temperature in the furnace; S605: Heat to 700-800℃ at 10℃ / min, hold for 120-240min, and then cool to room temperature with the furnace.

10. A multi-layered cranial repair scaffold, characterized in that: It includes an outer metal support layer, an inner bioceramic degradation and regeneration layer, and an intermediate transition interface layer.

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