Mirror image registration-based bone scaffold fusion design and preparation method

Abstract

The invention discloses a bone scaffold fusion design and preparation method based on mirror image registration, and the method comprises the steps: firstly, based on a three-dimensional medical image of a femoral defect region of a patient, combining an opposite-side complete femoral CT image, and achieving the automatic recognition and complementation of the defect region through the mirror image transformation and ICP registration technology; after defect boundary extraction is completed, three-dimensional reconstruction is carried out on the individualized outer contour of the left bone tissue, and an STL format model is exported. According to the femur functional partition characteristics, a Diamond structure is adopted in a cortical bone area to enhance mechanical support, and a Gyandroid structure is selected in a cancellous bone area to achieve porosity gradient filling, so that the permeability is optimized, and cell proliferation is promoted. Continuous transition among the structures is realized through a Sigmoid function, and the stability and the biological adaptability of the whole structure are improved. And finally, the stent model is subjected to selective laser melting, and a Zn-3Mg alloy material is utilized to complete printing manufacturing.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials and additive manufacturing technology, specifically relating to a bone scaffold design method and manufacturing process that integrates image recognition, 3D modeling, and a three-period minimal surface (TPMS) structure. This method is applicable to individualized reconstruction of long bone shaft defects, and is particularly suitable for the functional design and high-precision printing manufacturing of biodegradable metal implants. Background Technology

[0002] With the increasing prominence of bone defects, delayed fracture healing, and osteoporosis in the aging population, the clinical demand for personalized artificial bone scaffolds is constantly growing. Traditional repair materials such as titanium alloys and stainless steel, while possessing good mechanical strength, have densities and elastic moduli far exceeding those of natural human bone tissue, easily leading to stress shielding effects and secondary bone resorption, thus affecting long-term implantation stability and biofusion. Furthermore, traditional scaffold structures are mostly homogeneous solids with uncontrollable porosity, making it difficult to simultaneously meet the needs of mechanical support while also accommodating cell proliferation, nutrient exchange, and tissue regeneration. Triply Periodic Minimal Surface (TPMS) structures have gained widespread attention in the field of constructing biomimetic porous scaffolds due to their geometric advantages, including zero mean curvature, continuous interconnected channels, and adjustable parameters. TPMS structures are implicitly controlled, allowing for continuous adjustment of single-cell period, porosity, and topological form, while also possessing excellent mechanical load-bearing capacity and microenvironment adaptability, making them suitable for three-dimensional functional customization of bone scaffolds. Especially in long bones such as the femur, there are significant differences in the mechanical strength and permeability of the scaffold between the inner and outer functional zones, making it difficult for traditional single structures to provide targeted optimization.

[0003] While some studies have explored the mechanical properties and printability of TPMS structures, most remain focused on the basic level of homogeneous structures, lacking a systematic solution integrating "patient-specific morphological reconstruction, heterogeneous functional area filling, and printable manufacturing." Therefore, there is an urgent need to develop a bone scaffold design method that integrates individual anatomical data-driven approaches, heterogeneous modeling of structural and functional areas, and fabrication feasibility to achieve precise matching of bone defect areas, functional synergy, and effective fulfillment of personalized treatment needs.

[0004] The information disclosed in the background section is only for enhancing the understanding of the background of this invention, and therefore may contain information that does not constitute prior art known to those skilled in the art. Summary of the Invention

[0005] This invention provides a method for constructing a heterogeneous three-period minimal curved surface (TPMS) biomimetic bone scaffold and the scaffold itself. Three-dimensional image data of the femoral defect area are obtained through clinical CT scans. A medical image analysis method combining mirror processing of the contralateral intact femoral image with 3D point cloud extraction and ICP registration is employed. The three-period minimal curved surface (TPMS) is introduced into the design of porous bone implants, simulating the natural bone pore gradient porosity to match the distribution of human bone tissue. This effectively alleviates the stress shielding effect caused by the mismatch in elastic modulus of traditional metal implants. Existing scaffold design processes generally lack a systematic approach that integrates medical image recognition, structural modeling, functional simulation, and manufacturability assessment, making it difficult to achieve a closed loop from image input to structural output—design-verification-manufacturing—limiting its efficiency and reliability in rapid clinical translation.

[0006] A personalized load-bearing scaffold design method based on mirror registration and structural fusion includes:

[0007] (1) CT scans are used to acquire three-dimensional image data of the bone defect area, and CT images of the patient's contralateral intact femur are also acquired. The contralateral image is mirrored on the X-axis. The mirrored femur is precisely aligned to the coordinate system of the defective side bone image by three-dimensional point cloud extraction and ICP spatial registration algorithm. The spatial mask of the defect area is extracted by image difference logic. The spatial mask is converted into a three-dimensional mesh model by Marching Cubes algorithm and exported as an STL format.

[0008] (2) Import the STL format three-dimensional mesh model into the CAD modeling platform NTopology, and fill the heterogeneous TPMS structure according to the functional zoning requirements of bone tissue. The cortical bone region uses the Diamond structure to provide high mechanical support, and the cancellous bone region uses the Gyroid structure to improve permeability and conductivity. The porosity gradient, number of cycles and fusion function Sigmoid are set to ensure structural continuity and reasonable functional transition.

[0009] (3) The high permeability of the cancellous bone structure was explained by finite element analysis combined with average flow velocity and pressure difference parameters, and the Gyroid gradient scaffold was used as the gradient cancellous bone scaffold on the medial side of the femur.

[0010] (4) Based on the implicit surface fusion function Sigmoid, the cancellous bone scaffold and the homogeneous cortical bone scaffold are integrated to form a heterogeneous three-period minimal surface bionic bone scaffold with a smooth fusion transition structure.

[0011] (5) The bone scaffold is printed using selective laser melting (SLM) technology with Zn-3Mg pre-alloyed powder. The SLM parameters include laser power, scanning rate, layer thickness and scanning spacing. After printing, the powder is removed and ultrasonically cleaned.

[0012] In the method described above, the cancellous bone porosity gradient ranges from 30% to 70%.

[0013] In the method described above, the implicit function of the Gyroid structure is:

[0014]

[0015] where L is the wavelength, C is the offset, and x, y, z are three-dimensional space coordinates.

[0016] In the method described above, the implicit function of the Diamond structure is:

[0017]

[0018] In the method described above, the structure connection function is:

[0019]

[0020] where:

[0021]

[0022] The transition function α(z) is defined as:

[0023]

[0024] where: z0: the connection center height; s: the transition speed control factor,

[0025] This sigmoid function can geometrically ensure that:

[0026] When z << z0, the region where α(z) → 0 is a pure Diamond structure;

[0027] When z >> z0, α(z) → 1, and the region is a pure Gyroid structure;

[0028] When z ≈ z0, it is a smooth transition layer to avoid structural stress concentration caused by interface mutation.

[0029] In the method described above, the wavelength L is used to control the size of the structure unit cell. The larger L is, the smaller the unit cell is; the offset C is used to adjust the porosity and pore size morphology to achieve personalized regulation of the structural performance.

[0030] In the method described above, a finite element software is used to perform a steady-state laminar flow simulation on the Gyroid structure. The inlet flow velocity is set to 0.001 m / s, and the structure permeability is calculated through the pressure difference ΔP. The evaluation criterion is that the permeability is greater than 1×10*11 m 2 .

[0031] In the method described, the laser power of the SLM printing is 100W, the scanning speed is 800mm / s, the scanning spacing is 0.05mm, the layer thickness is 0.03mm, and a 90° cross-scanning strategy is adopted for each layer.

[0032] In the method described, the outer layer simulates cortical bone, requiring high structural stiffness and strength → a Diamond-type TPMS structure is adopted;

[0033] The inner layer simulates cancellous bone, requiring a lightweight structure and good permeability → a Gyroid-type TPMS structure is adopted;

[0034] The intermediate transition region structure must be continuous and the intensity must change smoothly → introduce functional parameters for transition.

[0035] The implicit function for connecting structures is defined as follows:

[0036]

[0037] in:

[0038]

[0039] The transition function α(z) is defined as:

[0040]

[0041] Where: z0: connection center height; s: transition speed control factor.

[0042] The sigmoid function is geometrically guaranteed to be:

[0043] When z << z0, the region α(z)→0 is a pure Diamond structure;

[0044] When z >> z0, α(z) → 1, and the region is a pure Gyroid structure;

[0045] When z≈z0, it is a smooth transition layer to avoid structural stress concentration caused by abrupt interface changes.

[0046] The resulting support structure is highly continuous in manufacturing and facilitates slicing and 3D printing, making it particularly suitable for high-precision metal additive manufacturing scenarios using selective laser melting (SLM).

[0047] In a preferred embodiment of the method for constructing a heterogeneous three-period minimal curved surface biomimetic bone scaffold, the size of the structural unit cell is controlled by the parameter L, and the larger L is, the smaller the unit cell size is; the porosity and pore shape of the structure are controlled by controlling the C value offset, and the overall performance is adjusted by adjusting the parameters to adjust the wall thickness and pore size of the overall structure.

[0048] CT scans acquire three-dimensional image data of the bone defect area, and simultaneously acquire CT images of the patient's contralateral intact femur. After X-axis mirroring of the contralateral image, the mirrored femur is precisely aligned to the coordinate system of the defective femur image using three-dimensional point cloud extraction and ICP spatial registration algorithms. The spatial mask of the defect area is then extracted using image difference logic. The spatial mask is converted into a three-dimensional mesh model using the Marching Cubes algorithm and exported in standard STL format for use as boundary input for subsequent TPMS modeling.

[0049] After the 3D mesh model is imported into the modeling platform NTopology, heterogeneous TPMS structures are filled into it according to the functional zoning requirements of bone tissue. In the cortical bone area, the Diamond structure is used to provide high mechanical support, while in the cancellous bone area, the Gyroid structure is used to optimize permeability and conductivity. At the same time, the porosity gradient, the number of cycles, and the fusion function Sigmoid are set to ensure structural continuity and reasonable functional transition.

[0050] The permeability of the Gyroid structure in the cancellous bone region was evaluated by finite element analysis. The optimal gradient scaffold with high permeability was used as the gradient cancellous bone scaffold on the medial side of the femur. The reasons for the excellent permeability of the Gyroid structure were explained by the average flow velocity and pressure difference parameters.

[0051] Based on the implicit surface fusion function Sigmoid, cancellous bone scaffolds and homogeneous cortical bone scaffolds are integrated to construct a heterogeneous three-period minimal surface biomimetic bone scaffold with a smooth fusion transition structure.

[0052] Heterogeneous three-period minimal curved surface biomimetic bone scaffolds were printed using Zn-3Mg pre-alloyed powder via selective laser melting (SLM). SLM parameters included laser power, scanning rate, layer thickness, and scanning spacing. After printing, the scaffolds underwent powder removal and ultrasonic cleaning.

[0053] In the method for constructing a heterogeneous three-period minimal curved surface biomimetic bone scaffold, the porosity of cortical bone and cancellous bone is 30% and 30% to 70%, respectively.

[0054] In the aforementioned method for constructing a heterogeneous three-period minimal surface biomimetic bone scaffold, the formula for the implicit structure function of the three-period minimal surface Gyroid structure is as follows:

[0055]

[0056] L is the wavelength, and C is called the offset.

[0057] In the method for constructing a heterogeneous three-period minimal surface biomimetic bone scaffold, the homogeneous cortical bone scaffold is a three-period minimal surface Diamond structure.

[0058] In the aforementioned method for constructing a heterogeneous three-period minimal surface biomimetic bone scaffold, the implicit structure function formula for the three-period minimal surface Diamond structure is as follows:

[0059]

[0060] In the method for constructing a heterogeneous three-period minimal curved surface biomimetic bone scaffold, the parameter L is used to control the size of the structural unit cell. The larger L is, the smaller the unit cell size. The porosity and pore shape of the structure are controlled by controlling the C value offset. The overall performance is adjusted by adjusting the parameters to adjust the wall thickness and pore size of the overall structure.

[0061] In the method for constructing a heterogeneous three-period minimal curved surface bionic bone scaffold, the heterogeneous three-period minimal curved surface bionic bone scaffold is prepared by an SLM printer.

[0062] The heterogeneous three-period minimal curved surface biomimetic bone scaffold is constructed through a personalized load-bearing bone scaffold design method based on mirror registration and structural fusion.

[0063] Compared with existing technologies, this invention has the following advantages: It selects different types of three-period minimal surface structures, combining excellent mechanical properties and excellent permeability through heterogeneous radial gradient fusion with a biomimetic femoral shaft, thereby improving the permeability and osteogenic capacity of the scaffold. A three-period minimal surface with an average curvature of zero is used as the basic framework, achieving a gradient distribution of porosity while maintaining structural stability. This biomimetic design draws inspiration from the pore distribution within natural bone tissue, constructing a porous system with functional gradient characteristics. Low-porosity structures generate an elastic modulus matching that of the host bone, while high-porosity structures, with interconnected connections, promote cell proliferation and further facilitate nutrient exchange and cell metabolism. The permeability of the biodegradable scaffold is closely related to its biocompatibility, therapeutic effect, and degradation kinetics. Permeability reflects the scaffold's ability to regulate material exchange through its internal pore structure, directly affecting nutrient delivery and cell migration. As a core parameter in scaffold design, permeability directly determines its effectiveness and safety in clinical application. A biodegradable scaffold is designed by constructing a heterogeneous biomimetic femoral structure through radial fusion. This invention selects a TPMS structure with zero average curvature, moderate elastic modulus, and large specific surface area to provide sufficient mechanical performance support for the biomimetic femur structure and reduce stress shielding. Furthermore, the tortuous and interconnected pores provide a site for cell proliferation, which is conducive to nutrient transport and greatly improves osteogenic capacity. Attached Figure Description

[0064] Various other advantages and benefits of the present invention will become apparent to those skilled in the art upon reading the detailed description of the preferred embodiments below. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. It is obvious that the drawings described below are merely some embodiments of the invention, and those skilled in the art can obtain other drawings based on these drawings without any inventive effort. Furthermore, the same reference numerals denote the same parts throughout the drawings.

[0065] In the attached diagram:

[0066] Figure 1 A schematic diagram of a personalized scaffold for a user's bone defect;

[0067] Figure 2 A flowchart for femoral defect identification and heterogeneous bone scaffold design;

[0068] Figure 3 3D modeling diagrams of three types of TPMS structures (Diamond, Gyroid);

[0069] Figure 4 The diagram shows the compressive stress-strain curve of the Diamond structure and a schematic diagram of the compressive strength error bars for three parallel compressed samples.

[0070] Figure 5 The diagram shows the permeability simulation results of the TPMS structure, including a schematic diagram comparing the average flow velocity and pressure difference.

[0071] Figure 6 This is a schematic diagram of the automatic identification and contralateral mirror reconstruction technology for bone defects based on CT images.

[0072] Figure 7 A schematic diagram of the fusion of a gradient bone scaffold structure in a bone defect;

[0073] Figure 8 This is a schematic diagram of the laser printing process for Zn-3Mg.

[0074] Figure 9 The surface morphology of Zn-3Mg blocky SEM and the surface morphology of Diamond structure SEM are shown.

[0075] The present invention will be further explained below with reference to the accompanying drawings and embodiments. Detailed Implementation

[0076] Specific embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While specific embodiments of the invention are shown in the drawings, it should be understood that the invention may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0077] It should be noted that certain terms are used in the specification and claims to refer to specific components. Those skilled in the art will understand that different terms may be used to refer to the same component. This specification and claims do not distinguish components based on differences in terminology, but rather on differences in function. The terms "comprising" or "including" used throughout the specification and claims are open-ended and should be interpreted as "comprising but not limited to." The following descriptions are preferred embodiments for carrying out the invention; however, these descriptions are for the purpose of understanding the general principles of the specification and are not intended to limit the scope of the invention. The scope of protection of this invention is determined by the appended claims.

[0078] To facilitate understanding of the embodiments of the present invention, further explanations and descriptions will be provided below with reference to the accompanying drawings and specific embodiments. The accompanying drawings do not constitute a limitation on the embodiments of the present invention.

[0079] like Figures 1 to 9 As shown, the method for constructing a heterogeneous three-period minimal curved surface biomimetic bone scaffold includes the following steps:

[0080] A method for bone fracture identification and 3D reconstruction of intact bone tissue from CT image data can automatically identify fracture regions and output STL format models suitable for modeling or printing without manual annotation. The method includes the following technical steps: Medical CT sequence reading and reconstruction: The SimpleITK framework is used to read DICOM sequence images and reconstruct 3D voxel images, supporting arbitrary anatomical locations and slice spacing. Bone tissue extraction: Dense bone tissue voxels are selected using a threshold method with a HU value greater than 200, and soft tissue and background are initially removed. Connected region selection: Through 3D connectivity analysis (scipy.ndimage.label), the largest volume connected regions are extracted as the main body of bone tissue, automatically excluding scattered bone fragments and scanning bed interference. Automatic fracture region identification: Cross-sectional images are scanned layer by layer along the Z-axis. If two or more connected regions appear in a layer, the layer is considered to have a fracture; the defect location is accurately located by statistically analyzing the range of fracture layer numbers. STL export: The Marching Cubes isosurface reconstruction algorithm is used to convert the bone tissue mask into a 3D polygon mesh, outputting it in STL format, compatible with CAD systems, TPMS structural modeling platforms, and 3D printing processes.

[0081] After the 3D mesh model is imported into the modeling platform NTopology, heterogeneous TPMS structures are filled into it according to the functional zoning requirements of bone tissue. In the cortical bone area, the Diamond structure is used to provide high mechanical support, while in the cancellous bone area, the Gyroid structure is used to optimize permeability and conductivity. At the same time, the porosity gradient, the number of cycles, and the Sigmoid function are set to ensure structural continuity and reasonable functional transition.

[0082] The permeability of the Gyroid structure in the cancellous bone region was evaluated by finite element analysis. The optimal gradient scaffold with high permeability was used as the gradient cancellous bone scaffold on the medial side of the femur. The reasons for the excellent permeability of the Gyroid structure were explained by the average flow velocity and pressure difference parameters.

[0083] Based on the sigmoid function method, cancellous bone scaffolds and homogeneous cortical bone scaffolds are integrated through functions to construct a heterogeneous three-period minimal curved surface biomimetic bone scaffold with a relatively smooth fusion transition structure.

[0084] Heterogeneous three-period minimal curved surface biomimetic bone scaffolds were printed using Zn-3Mg pre-alloyed powder via selective laser melting (SLM). SLM parameters included laser power, scanning rate, layer thickness, and scanning spacing. After printing, the scaffolds underwent powder removal and ultrasonic cleaning.

[0085] In a preferred embodiment of the method for constructing a heterogeneous three-period minimal curved surface biomimetic bone scaffold, the porosity gradient is 30% to 70%.

[0086] Based on the physiological characteristics of homogeneous cortical bone and gradient cancellous bone in the femur, this invention determines the target porosity range for both types of bone. According to the natural anatomical divisions and tissue physiological characteristics of the femur, the target porosity for the cortical bone region is set at 30% to simulate its density and high load-bearing capacity; the target porosity range for the cancellous bone region is 30%–70% to simulate its high permeability and cell-directing ability. This porosity design is determined based on physiological bone mineral density, Young's modulus of the human femur, and the requirements for osteocyte proliferation.

[0087] Constructing Gyroid structures and serving as gradient cancellous bone scaffolds;

[0088] The permeability of supports with different gradient structures was evaluated using finite element simulation. Under steady-state laminar flow conditions with an average inlet velocity of 0.001 m / s, the fluid pressure distribution inside the structure and the outlet pressure were calculated to obtain the pressure difference ΔP. The equivalent permeability of the structure was then calculated based on Darcy's law. Using Darcy permeability, average velocity, and pressure distribution as evaluation indicators, structures with permeability greater than 1 × 10⁻⁶ were selected. -11 m 2 Average flow velocity at 10 -2 -10 -3A structure with a uniform pressure field distribution within the range of m / s is considered as the optimal gradient design candidate for the homogeneous cortical bone scaffold of the medial femur.

[0089] Based on the sigmoid function method, cancellous bone scaffolds and homogeneous cortical bone scaffolds are integrated by the sigmoid function to construct a heterogeneous three-period minimal curved surface biomimetic bone scaffold with a relatively smooth fusion transition structure.

[0090] In a preferred embodiment of the method for constructing a heterogeneous three-period minimal curved surface biomimetic bone scaffold, the target porosity of homogeneous cortical bone is 30%, and the target porosity of gradient cancellous bone ranges from 30% to 70%.

[0091] In a preferred embodiment of the method for constructing a heterogeneous three-period minimal surface biomimetic bone scaffold, the implicit structure function formula of the three-period minimal surface Gyroid structure is as follows:

[0092]

[0093] L is the wavelength, C is called the offset, and x, y, and z are the independent variables that define the implicit function of TPMS.

[0094] In a preferred embodiment of the method for constructing a heterogeneous three-period minimal surface biomimetic bone scaffold, the homogeneous cortical bone scaffold is a three-period minimal surface Diamond structure.

[0095] In a preferred embodiment of the method for constructing a heterogeneous three-period minimal surface biomimetic bone scaffold, the implicit structure function formula of the three-period minimal surface Diamond structure is as follows:

[0096]

[0097] Specifically, the sigmoid function is used for linking. Example: A sigmoid function linking transition padding example for a Diamond-Gyroid structure.

[0098] This invention proposes an automatic identification and symmetrical reconstruction method for femoral defects based on medical CT images. The method extracts the damaged area through an algorithm and realizes three-dimensional mirror reconstruction, providing anatomical structural boundaries for personalized implant design.

[0099] (a) shows CT scan data of the patient's bilateral femurs, with significant bone defects on the left side and intact structure on the right side. This data was used as input for the bone reconstruction process.

[0100] (b) is a side view of the damaged femur on the left side. Combining the front and side views can help assess the spatial extent and location of the defect area and build a three-dimensional analysis coordinate basis.

[0101] (c) This invention performs preliminary segmentation of bone tissue by setting a HU threshold (usually HU>200), then extracts the largest bone block using a three-dimensional connected component analysis method, and analyzes the connectivity of the sliced ​​bone tissue layer by layer in the Z-axis direction. When a certain cross-sectional bone tissue layer is divided into two or more non-connected regions, it is automatically identified as a "fracture layer", thereby realizing the algorithmic identification and three-dimensional spatial localization of the defect area.

[0102] (d) After identifying the left defect area, the algorithm calls the patient's right complete femur data, obtains a symmetrical reference bone model through X-axis mirror inversion, and uses the point cloud-based ICP registration algorithm (Iterative ClosestPoint) to automatically align the mirrored right femur to the left defect area, completing the geometric fitting in spatial position.

[0103] (e) shows the final reconstructed left femur model, where the missing area is smoothly closed and filled by the mirrored reconstruction. The red and blue dashed lines indicate the aligned truncated reconstruction boundary. This complete bone model provides accurate three-dimensional anatomical input for subsequent porous structure design (TPMS heterogeneous nesting), finite element simulation, or personalized implant printing.

[0104] After completing femoral STL reconstruction and cannulated osteotomy, as Figure 6 As shown, the internal filling design of the TPMS structure is carried out, and the design goal is:

[0105] The outer layer simulates cortical bone, requiring high structural stiffness and strength → a Diamond-type TPMS structure is adopted;

[0106] The inner layer simulates cancellous bone, requiring a lightweight structure and good permeability → a Gyroid-type TPMS structure is adopted;

[0107] The intermediate transition region structure must be continuous and the intensity must change smoothly → introduce functional parameters for transition.

[0108] The implicit function for connecting structures is defined as follows:

[0109]

[0110] in:

[0111]

[0112] The transition function α(z) is defined as:

[0113]

[0114] Where: z0: connection center height; s: transition speed control factor.

[0115] The sigmoid function can geometrically ensure that:

[0116] When z << z0, the region where α(z) → 0 is a pure Diamond structure;

[0117] When z >> z0, α(z) → 1, and the region is a pure Gyroid structure;

[0118] When z ≈ z0, it is a smooth transition layer to avoid structural stress concentration caused by interface mutation.

[0119] The scaffold structure constructed in this way is highly continuous in manufacturing, and is convenient for slicing processing and three-dimensional printing, and is particularly suitable for the high-precision metal additive manufacturing scenario of selective laser melting (SLM).

[0120] In a preferred embodiment of the method for constructing a heterogeneous triply periodic minimal surface bionic bone scaffold, the parameter L is used to control the size of the structural unit cell. The larger L is, the smaller the unit cell size. By controlling the C value offset, the porosity and pore shape of the structure are controlled. By adjusting the parameters, the wall thickness and pore size of the overall structure are adjusted to achieve the purpose of adjusting the overall performance;

[0121] In a preferred embodiment of the method for constructing a heterogeneous triply periodic minimal surface bionic bone scaffold, a heterogeneous triply periodic minimal surface bionic bone scaffold is prepared by an SLM printing mechanism.

[0122] A heterogeneous triply periodic minimal surface bionic bone scaffold is constructed by the said method.

[0123] In one embodiment, see Figure 1Addressing the functional repair needs of complex bone defects, this system achieves end-to-end digital modeling, from anatomical structure recognition to structural partitioning modeling and additive manufacturing. First, CT images of the patient are acquired and the bone defect area is located. Using a mirror image of the contralateral healthy bone as a reference, the implantation environment of the defect area is assessed. The right-side image (intact femur) is mirrored along the X-axis. Using 3D point cloud extraction and an ICP (Iterative Closest Point) spatial registration algorithm, the mirrored right femur is precisely aligned to the coordinate system of the left-side defect femur image, and the spatial mask of the defect area is extracted. This extracted mask is then converted into a 3D mesh model using the Marching Cubes algorithm and exported in standard STL format for use as boundary input in subsequent TPMS modeling. During the structural construction phase, cortical bone and cancellous bone regions are distinguished based on the functional requirements of the patient's defect area. For the cortical bone portion, an external contour shell with bone-like stiffness is designed with "mechanical equivalence" as the goal. For the cancellous bone portion, an internal porous scaffold structure is designed to improve tissue ingrowth performance, guided by "permeability optimization." The final scaffold structure integrates the external contour configuration with the internal gradient porous structure, forming a continuous and manufacturable bone scaffold model through a smooth function transition. The constructed bone scaffold model, while meeting the requirements of human bone matching, is evaluated for its functional adaptability in the human body through a comprehensive assessment of permeability (average flow velocity and pressure difference) and mechanical properties (equivalent modulus and yield strength). The model is then imported into an additive manufacturing system to complete the physical construction of the personalized bone scaffold.

[0124] In one embodiment, a CT scan acquires three-dimensional image data of the bone defect area, and simultaneously acquires a CT image of the patient's contralateral (right) intact femur. After X-axis mirroring of the right image, the mirrored right femur is precisely aligned to the coordinate system of the left defect femur image using a three-dimensional point cloud extraction and ICP (Iterative Closest Point) spatial registration algorithm, and the spatial mask of the defect area is extracted. The extracted bone defect area mask is converted into a three-dimensional mesh model using the MarchingCubes algorithm and exported as a standard STL format for use as the boundary input for subsequent TPMS modeling.

[0125] The generated defect STL model is imported into the modeling platform (nTopology), and TPMS structures such as Diamond, Gyroid, or Schwarz P are embedded according to the functional zoning requirements of bone tissue to construct a heterogeneous porous bone scaffold with set porosity and number of cycles.

[0126] TPMS Structure Selection and Modeling: Implicit function models for three structures—Diamond (cortical bone), Gyroid, and Schwarz P (cancellous bone)—were established, with unit cell parameter L = 2.5, period control constant ω = 3–4, and porosity ranging from 30% to 70%. The TPMS structure used in this invention can be described by the following implicit functions.

[0127] A male femoral specimen with known bone defects was selected. The patient was 44 years old, weighed 85 kg, and was 185 cm tall. The specimen was collected in 2016 and presented as a typical case of fracture in the middle and lower segment of the left femur, with the fracture area covering approximately 6% of the total femoral length.

[0128] Imaging was performed using a clinical 64-slice spiral CT scanner. The acquisition parameters were as follows: slice thickness: 0.6 mm, resolution: 512×512, output format: DICOM sequence.

[0129] The original image was uniformly resampled to 1×1×1mm after processing with SimpleITK. 3 The voxels are then converted to NIfTI format for subsequent image processing.

[0130] This embodiment combines Figure 5 The CT image information shown verifies the practical feasibility of the algorithm-based automatic identification and reconstruction method for bone defects proposed in this invention. The CT image data used are bilateral femoral CT sequences of the patient, with consistent acquisition spacing, DICOM image format, and voxel spacing of (x_spacing, y_spacing, z_spacing) mm.

[0131] The processing procedure in this embodiment includes the following steps:

[0132] Step 1: Reading CT images of the left and right femurs

[0133] DICOM image sequences of the damaged left femur and the intact right femur were read separately, and 3D voxel images were reconstructed using the SimpleITK image reader. The reading code is as follows:

[0134] left_img=load_dicom_series("D: / data / left_femur")

[0135] right_img=load_dicom_series("D: / data / right_femur")

[0136] Step 2: Automatic extraction and defect identification of left-side bone tissue

[0137] Bone tissue was extracted from the left image using a HU threshold (HU>200) to form a binary mask. Then, the largest bone block was extracted as the main bone tissue using three-dimensional connected component analysis. The slices were scanned layer by layer along the Z-axis, and the Z-layer with two or more connected regions was identified as the fracture fracture layer, thereby automatically identifying the boundary of the defect area.

[0138] bone_mask=(left_np>200).astype(np.uint8)

[0139] labeled, _ = label(bone_mask)

[0140] mask=(labeled==np.argmax(np.bincount(labeled.ravel()[1:])+1)).astype(np.uint8)

[0141] fracture_layers=detect_fracture_layer(mask)

[0142] The test results show that a fracture occurs within approximately 240 to 260 layers along the Z-axis, corresponding to a physical height of approximately (260-240) × z_spacing mm, which verifies the automation and accuracy of the tomographic detection.

[0143] Step 3: Right femoral mirror image transformation and ICP registration

[0144] The complete right femur image was mirrored along the X-axis and used as a reconstruction reference model. Subsequently, it underwent spatial registration at the voxel level or point cloud level. The registration used the ICP (Iterative Closest Point) algorithm to ensure that the mirrored right femur was highly consistent with the left defect area in terms of posture and position in three-dimensional space, achieving symmetrical closure and completion of the fracture boundary.

[0145] right_mirror=sitk.Flip(right_img,[True,False,False])

[0146] After registration is completed, as follows Figure 5 As shown in (d), the mirrored right femur model is accurately superimposed on the left defect area, and the red and blue dashed lines mark the docking section, verifying the geometric rationality of the symmetrical reconstruction mechanism.

[0147] Step 4: Output of the reconstructed model on the left

[0148] After the fault boundary was closed, the overall left-side bone tissue model was smoothly stitched together to form a complete femoral structure, which was then converted into a triangular mesh structure using the Marching Cubes algorithm and finally exported as an STL format file.

[0149] marching_to_stl(mask,spacing,"D: / data / output / full_with_fracture.stl")

[0150] The exported STL model has a clear and continuous structure without any breaks or gaps.

[0151] The generated 3D bone model was imported into CATIA V5 for further fitting to reconstruct the femoral outer contour surface and the 3D boundary of the defect area. This model has potential applications in personalized implant design, TPMS structural filling, and finite element simulation.

[0152] After completing the femoral contour surface modeling, the shell thickness parameters are set according to the structural mechanics requirements of the bone scaffold. Preferably, the reconstructed outer shell model can be offset inward by 2mm to form an inner shell surface, thereby generating a scaffold shell with a closed space.

[0153] In one embodiment, the Diamond structure, known for its excellent mechanical properties, and the Gyriod structure, known for its strong cell proliferation capacity and excellent permeability, were selected for the design of cancellous and cortical bone. The porosity of human cortical bone is 30%, while that of cancellous bone ranges from 30% to 70%. This paper discusses scaffold design in two categories: cortical and cancellous bone. The Diamond structure, with its low porosity and high mechanical strength, was designed as a low-porosity homogeneous structure, while the Gyriod structure, with its high porosity and high permeability, was designed as a high-porosity gradient pore structure. Cortical bone was constructed using a Diamond homogeneous structure with a porosity of 30% and ω = 4. Cancellous bone was constructed using a Gyriod structure with a porosity transitioning from 30% to 70% along the x-axis, where ω = 3.

[0154] The periodic formula is expressed as follows:

[0155]

[0156] The formula for the implicit structure function of TPMS is as follows:

[0157] Table 1 Structural Equations

[0158]

[0159] In one embodiment, the method includes the following steps: First, based on the physiological characteristics of the femoral cortical bone and cancellous bone, the target porosity ranges for homogeneous cortical bone and gradient cancellous bone are defined; then, a Gyroid structure cancellous bone scaffold model is constructed; next, the permeability performance of the scaffold is analyzed through finite element analysis, demonstrating that the Gyroid structure is a highly permeable gradient scaffold serving as the medial cancellous bone of the femur, and the excellent permeability of the Gyroid structure is illustrated by the average flow velocity and pressure difference parameters; finally, the gradient scaffold is integrated with the homogeneous Diamond structure cortical bone based on the sigmoid function method to construct a heterogeneous femoral scaffold with a relatively smooth fusion transition structure, achieving synergistic optimization of osteoblast proliferation and material migration.

[0160] Specifically, the sigmoid function is used for linking. Example: A sigmoid function linking transition padding example for a Diamond-Gyroid structure.

[0161] After completing femoral STL reconstruction and cannulated osteotomy, as Figure 6 As shown, the internal filling design of the TPMS structure is carried out, and the design goal is:

[0162] The outer layer simulates cortical bone, requiring high structural stiffness and strength → a Diamond-type TPMS structure is adopted;

[0163] The inner layer simulates cancellous bone, requiring a lightweight structure and good permeability → a Gyroid-type TPMS structure is adopted;

[0164] The intermediate transition region structure must be continuous and the intensity must change smoothly → introduce functional parameters for transition.

[0165] The implicit function for connecting structures is defined as follows:

[0166] Φ(x,y,z)=(1-α(z))·Φ Diamond (x,y,z)+α(z)·Φ Gyroid (x,y,z)

[0167] in:

[0168] Φ Diamond (x,y,z)=cos(kx)cos(ky)cos(kz)-τ)

[0169] Φ Gyroid (x,y,z)=sin(kx)cos(ky)+sin(ky)cos(kz)+sin(kz)cos(kx)-τ

[0170] The transition function α(z) is defined as:

[0171]

[0172] Where: z0: connection center height; s: transition speed control factor.

[0173] The sigmoid function is geometrically guaranteed to be:

[0174] When z << z0, the region α(z)→0 is a pure Diamond structure;

[0175] When z >> z0, α(z) → 1, and the region is a pure Gyroid structure;

[0176] When z≈z0, it is a smooth transition layer to avoid structural stress concentration caused by abrupt interface changes.

[0177] The resulting support structure is highly continuous in manufacturing and facilitates slicing and 3D printing, making it particularly suitable for high-precision metal additive manufacturing scenarios using selective laser melting (SLM).

[0178] This example provides a gradient heterogeneous three-period minimal surface bone scaffold design method. The process is as follows: first, a three-period minimal surface lattice superstructure is designed, and then it is fabricated using an SLM printer.

[0179] The TPMS is a minimal surface with a crystal structure that periodically (with periodic variations along the X, Y, and Z axes) constructs a smooth, fully connected porous structure in three-dimensional space with an average curvature of zero.

[0180] This invention relates to three-dimensional digital models of two three-period minimal surface lattice structures, namely the Gyriod structure and the Diamond structure.

[0181] The following is the digital modeling process of the TPMS structure, which involves two implicit equations.

[0182]

[0183] A biomimetic femoral model was created using the 3D modeling software Ntopology for the three models mentioned above. Figure 2 Homogeneous cortical bone with a porosity of 30% was prepared using the Diamond structure, which exhibits excellent mechanical properties. By biasing the C value within the range of 0.7 to -0.7, a cancellous bone model with a linear porosity variation within the range of 30% to 70% was formed. The STL file generated by Ntopology software can be directly imported into an SLM printer.

[0184] like Figure 2 As shown, the process of femoral defect identification and heterogeneous bone scaffold design includes:

[0185] Image acquisition and preprocessing: Acquire CT data of the patient's left and right femurs, mirror the right side of the bone, and extract point cloud data.

[0186] Spatial registration and defect extraction: The left and right skeleton point clouds are aligned using the ICP algorithm to obtain the mask of the defect area.

[0187] 3D Reconstruction and Fitting: Marching Cubes was used to reconstruct the missing 3D model, which was then imported into CATIA for fitting and completion.

[0188] Structural design and model generation: Set the shell thickness, use Diamond and Gyroid structures to differentiate functions, and generate a closed bone scaffold STL model.

[0189] The SLM equipment used in this invention is the RC100-N1 (China National Additive Manufacturing Innovation Center). Argon gas was introduced before printing to ensure the oxygen content in the chamber was below 30 ppm under operating conditions. The chamber pressure was 5-9 mbar, and the substrate was heated to 100°C. All sample preparation processes were performed at a scan speed (V) of 80 mm / s, a hatch space (Hs) of 0.5 mm, a thickness (Ds) of 0.03 μm, and a scan path rotating 90° per layer. Figure 3 The printing process was performed using lasers with different power levels. Pure zinc was printed with a laser power of 80W, while Zn-3Mg was printed with a laser power of 100W. Based on this process, graded functional hierarchical Schwarz P structures, Gyriod structures, and homogeneous Diamond structures were fabricated.

[0190] Diamond homogeneous compression specimens were prepared according to GB / T 7314-2017 standard. Compression tests were conducted using a universal testing machine (Instron 5569, Instron, USA) at a beam speed of 1 mm / min, and the compression tests were terminated when 50% strain was reached.

[0191] Permeability analysis of a Gyroid gradient structure was performed using the Fluent module of ANSYS 2024 R2 commercial software. The overall flow velocity and pressure drop of the gradient model were obtained through simulation. The fluid simulation boundary conditions were: velocity inlet of 0.001 m / s, pressure outlet, stationary and non-slip wall, liquid water, and a steady-state laminar flow pattern. Post-processing was performed using CFD-Post to display the average flow velocity and pressure difference in each region.

[0192] See Figure 3To meet the differentiated functional needs of cortical and cancellous bone, the scaffold structure design adopts an "outer-inner integrated" strategy: the outer cortical bone region uses a mechanically uniform Diamond structure to achieve bone-like stiffness and continuous support; the inner cancellous bone region is based on a gradient periodic minimal surface (TPMS) design, constructing a Gyroid-type porous structure, with a frequency parameter set to ω=3 to achieve gradual control of the pore structure in space, thereby optimizing fluid permeability and tissue fusion potential. The figure shows two 3D models of TPMS scaffolds and their corresponding front and top views, used to simulate the filling structure of different tissue regions in the aforementioned scaffold construction process.

[0193] like Figure 4 Figure (a) describes the mechanical response of the Diamond structure compression sample during loading. The horizontal axis represents the material strain (unit deformation), and the vertical axis represents the corresponding stress (unit load strength). This curve allows observation of the material's elastic stage, yield point, and maximum load-bearing capacity (i.e., compressive strength). The maximum point on the curve represents the sample's ultimate compressive strength (approximately 19.83 MPa).

[0194] like Figure 4 The compressive strength error bar chart in (b) summarizes the compressive strength measurement results and error ranges of multiple samples (e.g., three samples), reflecting the performance differences and measurement fluctuations between samples. This helps to assess the uniformity of material preparation and the stability of mechanical properties. The error bars indicate the measurement uncertainty of strength, facilitating the assessment of data reliability.

[0195] Based on simulation results ( Figure 4 The main differences in permeability of the Gyroid structure are as follows: The Gyroid structure exhibits excellent permeability at low porosity (at the beginning of the gradient porosity), and its permeability stabilizes and shows a slight increase as porosity increases (30%-70%). Due to the high connectivity and uniformly distributed, gradient-widened channels of the Gyroid structure, efficient mass transport can be maintained even at lower porosity areas.

[0196] Based on simulation results ( Figure 4The total pressure difference ΔP is divided into unit cell pressure differences according to the number of unit cells N, which is ΔP = NΔPi. The pressure difference is divided into small units based on the unit cell. The Gyroid structure has smooth curvature, and the pressure transition within each unit cell is smooth with no obvious boundaries. The curvature change of the Gyroid structure is smooth, and the flow path within the unit cell has no abrupt changes. This geometric characteristic means that when the fluid passes through each unit cell, the pressure loss is mainly concentrated in local curvature change regions (such as surface inflection points), but the overall transition is gentle. Due to the high connectivity of the pore network, the flow direction of the fluid within the unit cell changes little, and the pressure gradient is mainly dominated by the differential properties of the surface, rather than the geometric discontinuities of the non-gradient unit cells.

[0197] Figure 5 This paper details the construction and manufacturing process of a bone scaffold model based on the patient's bone defect characteristics. First, the location and outer contour of the bone defect area were analyzed. Based on the patient's performance requirements, the Diamond scaffold, with its excellent mechanical properties, was selected as the outer contour of the bone scaffold, while the inner layer was filled using a Gyroid structural gradient. The two branches ultimately converge through "internal structure filling," and a "smoothing function" is used to achieve a seamless connection between the inner and outer structures, avoiding stress concentration and generating a complete "bone scaffold model." Finally, the model is materialized using "additive manufacturing" technology, completing the entire process from patient data collection to personalized implant manufacturing.

[0198] To achieve functional synergy and transitional continuity between cortical and cancellous bone structures in space, this paper utilizes a 3D reconstructed femur model of the patient. X-axis mirroring is performed on a complete CT image of the contralateral (right) femur. Combined with 3D point cloud extraction and ICP registration algorithms, the mirrored right femur is precisely aligned to the coordinate system of the defective side bone model. The spatial mask of the defect area is extracted, and the Marching Cubes algorithm is used to generate an STL model. Based on the principle of functional zoning of bone tissue, the outer region of the STL model adopts a cortical bone-like design with a Diamond structure to achieve good mechanical support properties. The inner region is filled with a gradient Gyroid structure, giving it excellent permeability and osteocyte proliferation potential. To avoid geometric discontinuities or stress concentrations during the splicing of porous structures, the Sigmoid function method is used for transition processing between the outer shell and the inner filling structure. The figure illustrates the construction process of the outer shell, the inner porous structure, and the fused overall heterogeneous porous scaffold, ultimately forming a personalized femoral scaffold model with continuous structure, clear functional zoning, and good manufacturability.

[0199] Specifically, the sigmoid function is used for linking. Example: A sigmoid function connection with transition padding in a Diamond-Gyroid structure;

[0200] After completing femoral STL reconstruction and cannulated osteotomy, as Figure 6As shown, the internal filling design of the TPMS structure is carried out, and the design goal is:

[0201] The outer layer simulates cortical bone, requiring high structural stiffness and strength → a Diamond-type TPMS structure is adopted;

[0202] The inner layer simulates cancellous bone, requiring a lightweight structure and good permeability → a Gyroid-type TPMS structure is adopted;

[0203] The intermediate transition region structure must be continuous and the intensity must change smoothly → introduce functional parameters for transition.

[0204] The implicit function for connecting structures is defined as follows:

[0205] Φ(x,y,z)=(1-α(z))·Φ Diamond (x,y,z)+α(z)·Φ Gyroid (x,y,z)

[0206] in:

[0207] Φ Diamond (x,y,z)=cos(kx)cos(ky)cos(kz)-τ

[0208] Φ Gyroid (x,y,z)=sin(kx)cos(ky)+sin(ky)cos(kz)+sin(kz)cos(kx)-τ

[0209] The sigmoid function α(z) is defined as:

[0210]

[0211] Where: z0: connection center height; s: transition speed control factor.

[0212] The sigmoid function is geometrically guaranteed to be:

[0213] When z << z0, the region α(z)→0 is a pure Diamond structure;

[0214] When z >> z0, α(z) → 1, and the region is a pure Gyroid structure;

[0215] When z≈z0, it is a smooth transition layer to avoid structural stress concentration caused by abrupt interface changes.

[0216] The resulting support structure is highly continuous in manufacturing and facilitates slicing and 3D printing, making it particularly suitable for high-precision metal additive manufacturing scenarios using selective laser melting (SLM).

[0217] To achieve high-precision fabrication of personalized bone scaffold structures, this study employed Selective Laser Melting (SLM) technology for additive manufacturing of the final scaffold model. The SLM printing process utilizes a layer-by-layer stacking strategy, and the figure illustrates a typical scanning path planning method in the SLM process. The printing direction is along the Z-axis (vertical direction), building layer by layer. The current n-th layer and the previous n+1-th layer use mutually perpendicular scanning paths, forming staggered scanning trajectories to improve interlayer bonding strength and reduce anisotropy. After each layer is melted in the horizontal plane (XY plane), the stage descends by one layer thickness to scan and melt the next layer. The 90° rotational scanning strategy shown in the figure is commonly used to improve the density and mechanical homogeneity of tissue components, particularly suitable for manufacturing complex three-dimensional continuous structures such as TPMS. During the printing process, process parameters of 100W laser power and 800mm / s were used to ensure that the complex scaffold structure maintains good structural integrity and surface quality while ensuring forming accuracy.

[0218] In summary, this invention utilizes mechanical testing to verify that Diamond meets the mechanical performance requirements of the femoral shaft, and uses finite element software to simulate the permeability performance of the TPMS structure. Two TPMS structures (Gyroid and Diamond) were selected, and based on the usage scenario, the two were fused according to the inner and outer femoral layers using the sigmoid function, resulting in a gradient femoral biomimetic structure with excellent comprehensive performance that combines the advantages of both.

[0219] In one embodiment, the method includes,

[0220] First, an algorithm is used to identify the actual location of the bone defect, extract the lesion location, and then fill the defect with a structure. Three TPMS models are initially established, with two models: the Gyroid structure designed as an internal gradient structure and the Diamond structure designed as external cortical bone. Fluid dynamics simulation experiments are used to verify the suitability of the Gyroid structure for filling within the femur, while mechanical experiments verify that the Diamond structure's elastic modulus does not cause stress shielding and can be used as cortical bone. A sigmoid function is used for fusion. Finally, a biodegradable Zn-3Mg bone implant is fabricated using a micromolecular laser (SLM) device.

[0221] CT scans acquire 3D image data of the bone defect area, and simultaneously acquire CT images of the patient's contralateral (right) intact femur. After X-axis mirroring of the right image, the mirrored right femur is precisely aligned to the coordinate system of the left defect femur image using 3D point cloud extraction and ICP (Iterative ClosestPoint) spatial registration algorithm. The spatial mask of the defect area is then extracted using image difference logic. The extracted bone defect area mask is converted into a 3D mesh model using the Marching Cubes algorithm and exported in standard STL format for use as boundary input for subsequent TPMS modeling.

[0222] After the 3D mesh model is imported into the modeling platform NTopology, heterogeneous TPMS structures are filled according to the functional zoning requirements of bone tissue. Diamond structures are used in the cortical bone area to provide high mechanical support, while Gyroid structures are used in the cancellous bone area to optimize permeability and conductivity. At the same time, porosity gradient and number of cycles are set to ensure structural continuity and reasonable functional transition.

[0223] This invention overcomes the performance bottlenecks of traditional homogeneous porous structures. Its gradient pore system effectively matches the performance requirements of different regions of the femur, promoting osteoblast migration and vascularization while reducing stress shielding effects. This provides a theoretical basis and technical path for the development of next-generation artificial femoral scaffolds. Based on the porosity-performance correlation analysis of three three-period minimal surface (TPMS) topologies (Gyroid, Diamond), this invention uses a structure with a porosity of 30% and a 30%-70% Gyroid gradient structure as core components, determined through mechanical performance testing. The Diamond structure is used on the outer side of the femur to achieve efficient load transfer due to its excellent mechanical properties, while the Gyroid structure is used on the inner side to promote osteoblast migration due to its high permeability. By using a radial smoothing function to eliminate the stress concentration problem caused by traditional splicing, a biomimetic composite scaffold with internal permeability and external rigidity is ultimately formed. This design solves the problem of the incompatibility between the mechanical and biological properties of traditional homogeneous porous femoral shafts, providing a new paradigm for bone scaffold development.

[0224] In one embodiment, traditional metal or polymer implant materials generally have homogeneous structures and untunable pore parameters, making it difficult to meet the differentiated mechanical strength and biopermeability requirements of bone tissue in different functional regions. This can easily lead to problems such as stress shielding effect and discontinuous bone healing. Currently, most porous bone scaffolds are based on a single type of TPMS structure, lacking a collaborative design strategy for heterogeneous structures oriented towards functional zones of bone tissue. They cannot effectively simulate the natural mechanical-functional gradient distribution of the femoral shaft, which is characterized by a dense outer shell and a porous inner core, affecting structural adaptability and functional regeneration capacity. There is also a lack of a modeling process based on individual patient CT image data that can achieve precise matching between the TPMS structure and the geometric shape of the bone defect. Insufficient implant boundary fit leads to stress concentration and increased risk of structural fracture in transition zones, severely restricting the engineering feasibility of personalized implantation. Existing scaffold design processes generally lack a systematic approach that integrates medical image recognition, structural modeling, functional simulation, and manufacturability assessment, making it difficult to achieve a closed loop from image input to structural output design-verification-manufacturing, thus limiting its efficiency and reliability in rapid clinical translation.

[0225] To address the aforementioned issues, this invention proposes an intelligent scaffold modeling and manufacturing method that integrates adjustable porosity TPMS structure, bone functional zone identification, continuous transition function fusion, permeability performance simulation evaluation, and SLM additive manufacturing based on Zn-3Mg biodegradable metal materials.

[0226] This invention overcomes the performance bottlenecks of traditional homogeneous porous structures. Its gradient pore system effectively matches the performance requirements of different regions of the femur, promoting osteoblast migration and vascularization while reducing stress shielding effects. This provides a theoretical basis and technical path for the development of next-generation artificial femoral scaffolds. Based on the porosity-performance correlation analysis of TPMS structures (Gyroid and Diamond structures), this invention uses a 30% porosity structure and a 30%-70% Gyroid gradient structure as core components, determined through mechanical property testing. The Diamond structure is used on the lateral side of the femur to achieve efficient load transfer due to its excellent mechanical properties, while the Gyroid structure is used on the inner side to promote osteoblast migration and nutrient transport due to its high permeability. By addressing the problem based on the sigmoid function, a biomimetic composite scaffold with internal permeability and external rigidity is ultimately formed. This design solves the problem of the incompatibility between the mechanical and biological properties of traditional homogeneous porous femoral shafts, providing a new paradigm for bone scaffold development.

[0227] In one embodiment, the method includes,

[0228] This example provides a gradient heterogeneous three-period minimal surface bone scaffold design method. The process is as follows: first, a three-period minimal surface lattice structure is designed, and then a biodegradable Zn-Mg alloy sample is prepared using SLM.

[0229] The TPMS is a minimal surface with a crystal structure that periodically (with periodic variations along the X, Y, and Z axes) constructs a smooth, fully connected porous structure in three-dimensional space with an average curvature of zero.

[0230] This invention relates to three-dimensional digital models of two three-period minimal surface lattice structures, namely the Gyriod type and the Diamond type.

[0231] The following is the digital modeling process of the TPMS structure, which involves three implicit equations.

[0232]

[0233] A biomimetic femoral model was created using the 3D modeling software Ntopology for the three models mentioned above. Figure 2 Homogeneous cortical bone with a porosity of 30% was prepared using the Diamond structure, which exhibits excellent mechanical properties. By biasing the C value within the range of 0.7 to -0.7, a cancellous bone model with a linear porosity variation within the range of 30% to 70% was formed. The STL file generated by Ntopology software can be directly imported into an SLM printer.

[0234] The SLM equipment used in this invention is the RC100-N1 (China National Additive Manufacturing Innovation Center). Gradient functional hierarchical Gyriod structures and homogeneous Diamond structures were prepared using Zn-3Mg pre-alloyed powder.

[0235] Diamond homogeneous compression specimens were prepared according to GB / T 7314-2017 standard. Compression tests were conducted using a universal testing machine (Instron 5569, Instron, USA) at a beam speed of 1 mm / min, and the compression tests were terminated when 50% strain was reached.

[0236] Permeability verification simulation: The above structural model was imported into ANSYS Fluent. The fluid was set to water, with an inlet velocity of 0.001 m / s, a steady-state laminar flow model, and an outlet pressure of normal. Pressure difference, average velocity, and fluid streamlines were extracted to evaluate the permeability performance of different TPMS structures under the given porosity conditions. This simulation only illustrates the superior permeability structure type (Gyroid).

[0237] Based on simulation results ( Figure 4The main differences in permeability between the Gyroid structure and the γroid structure are as follows: The Gyroid structure exhibits excellent permeability at low porosity (at the beginning of the gradient porosity), and its permeability stabilizes and shows a slight increase as the porosity increases (30%-70%). Due to the high connectivity and uniformly distributed gradient-widened channels of the Gyroid structure, efficient mass transport can be maintained even at lower porosity areas.

[0238] Based on simulation results ( Figure 4 The total pressure difference ΔP is divided into unit cell pressure differences according to the number of unit cells N, which is ΔP = NΔPi. The pressure difference is divided into each small unit cell. The Gyroid structure has a smooth curvature, and the pressure transition in each unit cell is smooth with no obvious partition boundaries. The curvature change of the Gyroid structure is smooth, and the flow path does not have abrupt changes within the unit cell.

[0239] A male femoral specimen with known bone defects was selected. The patient was 44 years old, weighed 85 kg, and was 185 cm tall. The specimen was collected in 2016 and presented as a case of typical bone fracture in the middle and lower segment of the left femur, with the defect area covering approximately 6% of the total femoral length.

[0240] Imaging was performed using a clinical 64-slice spiral CT scanner. The acquisition parameters were as follows: slice thickness: 0.6 mm, resolution: 512×512, output format: DICOM sequence.

[0241] The original image was uniformly resampled to 1×1×1mm after processing with SimpleITK. 3 The voxels are converted to NIfTI format for subsequent image recognition model input.

[0242] This embodiment combines Figure 5 The CT image information shown verifies the practical feasibility of the algorithm-based automatic identification and reconstruction method for bone defects proposed in this invention. The CT image data used are bilateral femoral CT sequences of the patient, with consistent acquisition spacing, DICOM image format, and voxel spacing of (x_spacing, y_spacing, z_spacing) mm. The image data is stored in the folders D: / data / left_femur and D: / data / right_femur.

[0243] The processing procedure in this embodiment includes the following steps:

[0244] Step 1: Reading CT images of the left and right femurs

[0245] DICOM image sequences of the damaged left femur and the intact right femur were read separately, and 3D voxel images were reconstructed using the SimpleITK image reader. The reading code is as follows:

[0246] left_img=load_dicom_series("D: / data / left_femur")

[0247] right_img=load_dicom_series("D: / data / right_femur")

[0248] Step 2: Automatic extraction and defect identification of left-side bone tissue

[0249] Bone tissue was extracted from the left image using a HU threshold (HU>200) to form a binary mask. Then, the largest bone block was extracted as the main bone tissue using three-dimensional connected component analysis. The slices were scanned layer by layer along the Z-axis, and the Z-layer with two or more connected regions was identified as the fracture fracture layer, thereby automatically identifying the boundary of the defect area.

[0250] bone_mask=(left_np>200).astype(np.uint8)

[0251] labeled, _ = label(bone_mask)

[0252] mask=(labeled==np.argmax(np.bincount(labeled.ravel()[1:])+1)).astype(np.uint8)

[0253] fracture_layers=detect_fracture_layer(mask)

[0254] The test results show that a fracture occurs within approximately 240 to 260 layers along the Z-axis, corresponding to a physical height of approximately (260-240) × z_spacing mm, which verifies the automation and accuracy of the tomographic detection.

[0255] Step 3: Right femoral mirror image transformation and ICP registration

[0256] The complete right femur image was mirrored along the X-axis and used as a reconstruction reference model. Subsequently, it underwent spatial registration at the voxel level or point cloud level. The registration used the ICP (Iterative Closest Point) algorithm to ensure that the mirrored right femur was highly consistent with the left defect area in terms of posture and position in three-dimensional space, achieving symmetrical closure and completion of the fracture boundary.

[0257] right_mirror=sitk.Flip(right_img,[True,False,False])

[0258] After registration, the mirrored right femur model was accurately superimposed on the left defect area, and the docking section was marked by red and blue dashed lines, verifying the geometric rationality of the symmetrical reconstruction mechanism.

[0259] Step 4: Output of the reconstructed model on the left

[0260] After the fault boundary was closed, the overall left-side bone tissue model was smoothly stitched together to form a complete femoral structure, which was then converted into a triangular mesh structure using the Marching Cubes algorithm and finally exported as an STL format file.

[0261] marching_to_stl(mask,spacing,"D: / data / output / full_with_fracture.stl")

[0262] The exported STL model has a clear and continuous structure without any breaks or gaps.

[0263] The generated 3D bone model was imported into CATIA V5 for further fitting to reconstruct the femoral outer contour surface and the 3D boundary of the defect area. This model has potential applications in personalized implant design, TPMS structural filling, and finite element simulation.

[0264] After completing the femoral contour surface modeling, the shell thickness parameters are set according to the structural mechanics requirements of the bone scaffold. Preferably, the reconstructed outer shell model can be offset inward by 2mm to form an inner shell surface, thereby generating a scaffold STL model with a closed space.

[0265] Based on the principle of functional zoning of bone tissue, the outer region of the STL model adopts a cortical bone-like design with a Diamond structure to achieve good mechanical support properties; the inner region is filled with a gradient Gyroid structure, which gives it excellent permeability and osteocyte proliferation potential.

[0266] To avoid geometric discontinuities or stress concentrations during the splicing of porous structures, the Sigmoid function method is used to transition between the outer shell and the inner filling structure.

[0267] Based on the patient's performance requirements for the bone scaffold, the Diamond scaffold with excellent mechanical properties has been selected as the outer contour of the bone scaffold, and the inner layer is filled with Gyroid structural gradient.

[0268] Example: Transition padding example of sigmoid function connection in Diamond-Gyroid structure

[0269] After completing femoral STL reconstruction and cannulated osteotomy, as Figure 6 As shown, the internal filling design of the TPMS structure is carried out, and the design goal is:

[0270] The outer layer simulates cortical bone, requiring high structural stiffness and strength → a Diamond-type TPMS structure is adopted;

[0271] The inner layer simulates cancellous bone, requiring a lightweight structure and good permeability → a Gyroid-type TPMS structure is adopted;

[0272] The intermediate transition region structure must be continuous and the intensity must change smoothly → introduce functional parameters for transition.

[0273] The implicit function for connecting structures is defined as follows:

[0274] Φ(x,y,z)=(1-α(z))·Φ Diamond (x,y,z)+α(z)·Φ Gyroid (x,y,z)

[0275] in:

[0276] Φ Diamond (x,y,z)=cos(kx)cos(ky)cos(kz)-τ

[0277] Φ Gyroid (x,y,z)=sin(kx)cos(ky)+sin(ky)cos(kz)+sin(kz)cos(kx)-τ

[0278] The transition function α(z) is defined as:

[0279]

[0280] Where: z0: connection center height; s: transition speed control factor.

[0281] The sigmoid function is geometrically guaranteed to be:

[0282] When z << z0, the region α(z)→0 is a pure Diamond structure;

[0283] When z >> z0, α(z) → 1, and the region is a pure Gyroid structure;

[0284] When z≈z0, it is a smooth transition layer to avoid structural stress concentration caused by abrupt interface changes.

[0285] The resulting support structure is highly continuous in manufacturing and facilitates slicing and 3D printing, making it particularly suitable for high-precision metal additive manufacturing scenarios using selective laser melting (SLM).

[0286] Printing and Post-processing: This example uses a Zn-3Mg alloy with good biocompatibility and biodegradability as the bone scaffold material, which can gradually degrade and participate in the bone regeneration process after implantation. Selective laser melting (SLM) was used for manufacturing, with the Zn-3Mg alloy powder having an average particle size of 30 μm. A commercial SLM system was used for printing, and the printing environment was maintained under a low-oxygen argon protective atmosphere (O2 content <100 ppm). The substrate was preheated to 100°C to reduce cracks and residual stress. Printing parameters included: laser power of 100 W, scanning speed of 80 mm / s, layer thickness of 30 μm, scanning spacing of 100 μm, and a 90° rotation of the scanning path for each layer to improve structural uniformity and density. After printing, the sample was polished and ultrasonically treated to remove adhering powder, and the surface morphology and defects were observed using a scanning electron microscope.

[0287] Target porosity ranges were determined: Based on the physiological characteristics of homogeneous cortical bone and gradient cancellous bone, their target porosity ranges were determined (30% and 30%-70%, respectively). This ensures that the designed scaffold can mimic the mechanical properties and biocompatibility of real bone tissue.

[0288] Selection and construction of TPMS structure:

[0289] Gyroid: Due to its high connectivity and uniform distribution, it is particularly suitable for simulating the high permeability and gradual porosity of cancellous bone.

[0290] Diamond structure: Due to its excellent mechanical properties, it has been selected as an ideal model for simulating cortical bone.

[0291] Finite element analysis to evaluate permeability: By simulating and analyzing the permeability of different structures, the most suitable structure for use as a scaffold in the medial femoral cancellous bone is selected. This method helps ensure the effectiveness of the scaffold in practical applications, especially in promoting material transport.

[0292] Parameter control and adjustment: By adjusting the L and C values, the size of the structural unit cell, porosity, and transitional structural morphology can be controlled to achieve optimal mechanical properties.

[0293] Applications of SLM printing technology: By selecting specific SLM equipment and process parameters for 3D printing, the transformation from a digital model to a physical stent can be achieved. This method not only ensures manufacturing precision but also allows for the customization of personalized stents according to the specific needs of patients.

[0294] Mechanical testing and verification: The prepared stent was subjected to a compression test according to national standards to verify whether its mechanical properties met the requirements. This step is crucial for ensuring the long-term stability and safety of the stent in the body.

[0295] Fluid permeability simulation verification: To ensure the designed stent possesses good blood or tissue fluid permeability, this invention further introduces fluid simulation analysis to compare and evaluate the permeability performance of different structural combinations. A flow model is constructed based on the finite element method, setting inlet pressure and outlet boundary conditions to simulate the velocity distribution and pressure gradient of the liquid under different structures. The equivalent permeability is calculated according to Darcy's law. Combining mechanical simulation and experimental verification, the design scheme with the best match between permeability performance and structural strength is selected, providing a theoretical basis and design support for the functional stability of the stent during actual implantation.

[0296] Method for obtaining defect location from CT images: In order to achieve high-precision matching between the scaffold and the defective bone area, this invention first obtains three-dimensional image data of the patient's bilateral femurs through CT scans. By using the mirroring processing of the contralateral healthy bone combined with the ICP point cloud registration algorithm, the mirrored healthy side model is accurately aligned to the coordinate system of the defective side. Then, the bone defect area is extracted by image difference, and the three-dimensional model in STL format is reconstructed with the Marching Cubes algorithm, providing accurate boundary input for subsequent TPMS structure modeling.

[0297] Applications of the sigmoid function formula: As a transitional sigmoid function, it smoothly connects different TPMS structures, avoiding abrupt changes between structures and improving the consistency and stability of the overall structure. Sigmoid function method: This method is used to seamlessly integrate cancellous bone scaffolds with homogeneous cortical bone scaffolds, forming a monolithic structure with continuous mechanical properties and gradually varying porosity. This design helps reduce stress concentration points and improve the overall structural stability.

[0298] Figure 9 Image (a) shows the microstructure of the Zn-3Mg alloy after printing. The structure is uniform and the surface is smooth, with no cracks or other defects observed, demonstrating that the printing process successfully achieved a high-quality surface feature. The pore size in this image is labeled as 100 μm, indicating good porosity control in the alloy, meeting design requirements. The printing density exceeds 99.5%, exhibiting excellent compactness and low porosity, ensuring the material's mechanical properties and structural stability.

[0299] Figure 9 Figure (b) shows the microstructure of the Diamond structure, with a dimension of 801.8 μm. The structure exhibits a regular and symmetrical geometry, conforming to the design requirements of the Triple Period Minimal Surface (TPMS). The Diamond structure possesses high mechanical support capacity, making it suitable for use as a scaffold to simulate cortical bone regions, further demonstrating its potential for application in the biomedical field.

[0300] Although embodiments of the present invention have been described above in conjunction with the accompanying drawings, the present invention is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art can make many other forms based on the guidance of this specification and without departing from the scope of protection of the claims of the present invention, and all of these are within the scope of protection of the present invention.

Claims

1. A method for designing and fabricating a bone scaffold based on mirror registration, characterized in that, Includes the following steps: (1) CT scans are used to obtain three-dimensional image data of the bone defect area and CT images of the patient’s contralateral intact femur are obtained at the same time. The contralateral image is mirrored on the X-axis. The mirrored femur is precisely aligned to the coordinate system of the bone image of the defect side by three-dimensional point cloud extraction and ICP spatial registration algorithm. The spatial mask of the defect area is extracted by image difference logic. The spatial mask is converted into a three-dimensional mesh model using the Marching Cubes algorithm and exported as an STL format; (2) Import the STL format three-dimensional mesh model into the CAD modeling platform NTopology, and fill the heterogeneous TPMS structure according to the functional zoning requirements of bone tissue. The cortical bone region uses the Diamond structure to provide high mechanical support, and the cancellous bone region uses the Gyroid structure to improve permeability and conductivity. The porosity gradient, number of cycles and fusion function Sigmoid are set to ensure structural continuity and reasonable functional transition. (3) The high permeability of the cancellous bone structure was explained by finite element analysis combined with average flow velocity and pressure difference parameters, and the Gyroid gradient scaffold was used as the gradient cancellous bone scaffold on the medial side of the femur. (4) Based on the implicit surface fusion function Sigmoid, the cancellous bone scaffold and the homogeneous cortical bone scaffold are integrated to form a heterogeneous three-period minimal surface bionic bone scaffold with a smooth fusion transition structure. (5) The bone scaffold is printed using selective laser melting (SLM) technology with Zn-3Mg pre-alloyed powder. The SLM parameters include laser power, scanning rate, layer thickness and scanning spacing. After printing, the powder is removed and ultrasonically cleaned.

2. The method according to claim 1, characterized in that, Preferably, the pore size gradient transitions, with the porosity gradient of the cancellous bone ranging from 30% to 70%.

3. The method according to claim 1, characterized in that, The implicit function of the Gyroid structure is: Where L is the wavelength, C is the offset, and x, y, z are the three-dimensional spatial coordinates.

4. The method according to claim 1 or 3, characterized in that, The implicit functions of the Diamond structure are:

5. The method according to claim 1, characterized in that, The structure connection function is: in: The transition function α(z) is defined as: Where: z0: connection center height; s: transition speed control factor. The sigmoid function is geometrically guaranteed to be: When z << z0, the region α(z)→0 is a pure Diamond structure; When z >> z0, α(z) → 1, and the region is a pure Gyroid structure; When z≈z0, it is a smooth transition layer to avoid structural stress concentration caused by abrupt interface changes.

6. The method according to claim 5, characterized in that, The wavelength L is used to control the size of the structural unit cell; the larger L is, the smaller the unit cell is. The offset C is used to adjust the porosity and pore size morphology to achieve personalized control of structural performance.

7. The method according to claim 1, characterized in that, Steady-state laminar flow simulation of the Gyroid structure was performed using finite element method (FEM) software. The inlet velocity was set to 0.001 m / s. The permeability of the structure was calculated using the pressure difference ΔP, and the evaluation criterion was a permeability greater than 1 × 10⁻⁶. -11 m 2 .

8. The method according to claim 1, characterized in that, The SLM printer uses a laser power of 100W, a scanning speed of 800mm / s, a scanning spacing of 0.05mm, a layer thickness of 0.03mm, and employs a 90° cross-scanning strategy for each layer.

9. A heterogeneous three-period minimal curved surface biomimetic bone scaffold, characterized in that, It is prepared by the method according to any one of claims 1-8.

Images