Degradable gradient porous Zn (at) beta-TCP composite scaffold for bone defect repair and preparation method of degradable gradient porous Zn (at) beta-TCP composite scaffold

Abstract

The invention belongs to the technical field of metal powder processing, and discloses a degradable gradient porous Zn (at) beta-TCP composite scaffold for bone defect repair and a preparation method. Wherein in the Zn (at) beta-TCP composite material of the stent, preferably, the volume fractions of Zn and beta-TCP are 97 vol.% and 3 vol.%; the internal structure of the stent is a gradient porous structure, specifically, a three-circle minimal curved surface is used as a pore topological structure, and the pore diameter is in linear transition of 700 + / -50 [mu] m to 1100 + / -50 [mu] m. The preparation method comprises the following steps: designing a gradient porous scaffold model through computer-aided design, taking Zn as a metal matrix, taking beta-TCP as a reinforcement phase, and preparing the Zn-beta-TCP composite scaffold with the gradient porous structure by using a laser powder melting technology. The gradient structure design in the prepared stent can provide a larger space for adhesion and proliferation of osteoblasts, and transmission of nutrient substances and ingrowth of bone tissues are facilitated.

Description

Technical Field

[0001] This invention belongs to the field of metal powder processing technology and relates to composite material scaffolds that can be used in biomedical materials. Specifically, it is a biodegradable gradient porous Zn@β-TCP composite material scaffold for bone defect repair and its preparation method. Background Technology

[0002] Bone defects are a common orthopedic condition. Smaller defects can heal spontaneously or be treated with conventional fracture management methods. However, when the defect reaches a "critical bone defect length," bone grafting surgery is required for repair. Compared to traditional bone defect repair materials such as polylactic acid, collagen, and hydroxyapatite, biodegradable metals possess superior mechanical properties and unique biodegradability, making them a novel type of bone defect repair material. Among these, zinc-based materials exhibit a more suitable degradation rate compared to magnesium-based and iron-based materials, but lack certain osteogenic activity. β-tricalcium phosphate (β-TCP), as a bioceramic material, possesses excellent osteogenic induction capabilities. Adding it to zinc-based materials not only improves osteogenic activity but also allows for the regulation of the material's degradation properties.

[0003] From an application perspective, human bone has an interconnected porous structure. Therefore, designing zinc-based materials with a porous structure can not only provide space for tissue growth but also effectively reduce the stress shielding effect caused by material implantation. Furthermore, bone defects vary in structure, shape, and size, and the internal porous structure (including porosity, pore diameter, pore distribution, and pore shape) also differs significantly between different bone locations. Therefore, providing patients with bone defect repair materials that offer customizable macroscopic shapes and adjustable internal porous structures is crucial for clinical application. Summary of the Invention

[0004] To address the aforementioned issues, the present invention aims to prepare a Zn@β-TCP composite scaffold with a specific gradient porous structure using pure zinc (Zn) metal powder and β-tricalcium phosphate (β-TCP) particles as raw materials. This scaffold is prepared by ball milling and then processed using laser powder melting technology. By altering the material composition and pore structure, the mechanical properties, degradation rate, and osteogenic activity of the Zn@β-TCP composite scaffold are controlled, achieving stable and reliable bone defect repair.

[0005] This invention is achieved using the following technical solution: In a first aspect, the present invention provides a biodegradable gradient porous Zn@β-TCP composite material scaffold for bone defect repair, wherein the volume fraction of Zn in the Zn@β-TCP composite material of the scaffold is 95-99 vol.% and the volume fraction of β-TCP is 1-5 vol.%; the internal structure of the scaffold is a gradient porous structure.

[0006] More preferably, the gradient porous structure uses a three-circle minimal surface (TPMS) as the pore topology, and the pore diameter linearly transitions from 700±50μm to 1100±50μm from the first layer to the last layer.

[0007] More preferably, in the Zn@β-TCP composite material of the scaffold, the volume fraction of Zn is 97 vol.% and the volume fraction of β-TCP is 3 vol.%.

[0008] Secondly, the present invention provides a method for preparing a biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair, comprising the following steps: Step (1), Ingredients and Mixing Weigh out the raw materials zinc powder and β-TCP particles, and ball mill them together to form a mixed powder. Step (2) Structural Design The nTopology software was used to design the topology structure, creating 2.5×2.5×2.5mm sheet-like Gyroid unit cells, which were arranged in an array with a 10×10×10mm lattice network structure. The lattice wall thickness was set along the unidirectional gradient direction, ranging from 0.25 to 0.70mm from left to right, corresponding to aperture sizes of 700±50μm to 1100±50μm. A three-circle minimal surface structure model was constructed, and the model was exported as an STL file. Step (3): Set process parameters and slice the model. In the Magics software, select the BLT-S210 platform, import the model into the platform, and set the printing parameters in the BLT-BP software. Then, perform model segmentation and slicing, and import the segmented model into the actual BLT-S210 device for printing. Step (4): Laser powder melting to prepare Zn@β-TCP composite scaffold The mixed powder is loaded into the powder tank of the BLT-S210 equipment for printing; After printing is complete, wait for the substrate temperature to drop to room temperature, open the door to remove the substrate, and take the support sample off the substrate. Step (5) Surface treatment Excess powder was removed from the pores of the scaffold sample. The sample was then sandblasted to remove unmelted adhering powder from the surface, and the residual sand was removed. The sandblasted sample scaffold was placed in deionized water for ultrasonic cleaning and drying to obtain a gradient porous Zn@β-TCP composite material scaffold.

[0009] More preferably, in step (3), the printing parameters are: laser power of 40W, laser scanning speed of 200mm / s, laser scanning spacing of 0.04mm, layer thickness of 0.02mm, and a zigzag scanning path with a rotation of 67° for each layer.

[0010] More preferably, in step (4), before printing begins, the height of the substrate is adjusted to be flush with the height of the powder tank; argon is used as a protective gas for purging, the argon pressure is set to 4Pa, and the fan is turned on when the oxygen content in the printing chamber is less than 0.5ppm; the substrate heating is turned on when the oxygen content in the printing chamber is less than 0.3ppm, the substrate is heated to 100°C, and printing begins when the oxygen content in the printing chamber is less than 0.01ppm.

[0011] This invention utilizes computer-aided design of a gradient porous model, employing Zn powder as the metal matrix and β-TCP particles as the reinforcing phase, to fabricate a gradient porous biodegradable Zn@β-TCP composite scaffold using laser powder melting technology. During laser powder melting, excessively rapid heating and cooling can lead to insufficient dispersion of β-TCP in the molten pool, thus affecting the molding quality of the Zn@β-TCP composite scaffold. This invention effectively improves the dispersion of β-TCP in the Zn matrix by preheating the substrate and employing appropriate laser power and scanning speed, thus solving the technical problem of molding difficulties caused by the large melting point difference between Zn and β-TCP during laser powder melting.

[0012] The gradient porous Zn@β-TCP composite scaffold prepared in this invention exhibits good mechanical properties and a suitable degradation rate. Its fully interconnected pore structure provides ample space for osteoblast adhesion and proliferation, facilitating nutrient transport and the ingrowth of new bone tissue. The gradient porous structure of the Zn@β-TCP composite scaffold matches the mechanical properties and growth rate of human cortical bone to trabecular bone, avoiding nonunion caused by stress shielding effects and balancing local degradation rates with local bone growth rates. Testing showed that the prepared Zn@β-TCP composite scaffold achieved a density of over 97.50%, a compressive yield strength of 39.15 MPa, a compressive elastic modulus of 2.48 GPa, and a degradation rate of 5.73% after immersion in simulated body fluid for 28 days.

[0013] This invention is rationally designed and has good clinical application value. Attached Figure Description

[0014] Figure 1 The preset model of the gradient porous Zn@β-TCP composite material scaffold is shown, where A is the overall view of the preset model and B is the cross-sectional view.

[0015] Figure 2The image shows a molded sample of a gradient porous Zn@β-TCP composite scaffold, where A is an overall view of the molded sample and B is a cross-sectional view.

[0016] Figure 3 This figure represents the degradation and weight loss of the gradient porous Zn@β-TCP composite scaffold in simulated body fluid.

[0017] Figure 4 The diagram shows the compressive stress-strain curve of the gradient porous Zn@β-TCP composite scaffold. Detailed Implementation

[0018] The specific embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0019] This invention discloses a biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair. Using Zn powder as the metal matrix and β-TCP particles as the ceramic particle reinforcement phase, the powders are mixed and then fabricated using computer-aided design and laser powder melting technology to create a Zn@β-TCP composite scaffold with a gradient porous structure. The addition of the β-TCP reinforcement phase not only improves the mechanical properties of the Zn matrix but also accelerates scaffold degradation. The fully interconnected porous structure provides greater space for osteoblast adhesion and proliferation, facilitating nutrient transport and bone tissue ingrowth. Furthermore, the gradient porous structure design can match the mechanical properties and growth rate from cortical bone to trabecular bone.

[0020] I. The chemical materials used in this embodiment are: zinc powder (powder diameter between 15 and 53 μm), β-TCP particles (particle diameter less than 200 nm), anhydrous ethanol, deionized water, sodium chloride, sodium bicarbonate, sodium carbonate, potassium chloride, dipotassium hydrogen phosphate trihydrate, magnesium chloride hexahydrate, 4-hydroxyethylpiperazine ethanesulfonic acid, calcium chloride, sodium sulfate, chromium trioxide, graphite paper, sandpaper, and argon gas. The quantities of the chemical substances used are proportioned according to preset values, and are measured in grams (g), liters (L), milliliters (mL), and millimeters (mm).

[0021] The laser additive manufacturing equipment used in this embodiment is an existing BLT-S210 laser powder bed melting equipment, which is operated in sequence according to the operating requirements.

[0022] II. The mechanical strength comparison of Zn@β-TCP composite scaffolds with different β-TCP volume fractions is as follows: Zn@β-TCP composite scaffolds with different volume fractions (the total volume fraction of Zn and β-TCP is 100 vol.%) were prepared using laser powder melting forming technology under the same process parameters (as described in the examples in Part IV below): Zn@1β-TCP (where 1 represents a volume fraction of 1 vol.%), Zn@3β-TCP (where 3 represents a volume fraction of 3 vol.%), and Zn@5β-TCP (where 5 represents a volume fraction of 5 vol.%).

[0023] The compressive mechanical properties of the above samples were tested using a universal testing machine. The results were as follows: the yield strength of the Zn@1β-TCP composite scaffold was 102.31 MPa, the yield strength of the Zn@3β-TCP composite scaffold was 133.77 MPa, and the yield strength of the Zn@5β-TCP composite scaffold was 119.76 MPa. These results indicate that the Zn@β-TCP composite scaffold exhibits the highest mechanical strength when the volume fraction of β-TCP is 3%.

[0024] In specific implementation, the weighing and mixing of raw materials during the preparation of the Zn@β-TCP composite scaffold are as follows: Before mixing, the raw materials need to be weighed. Each mixing operation uses 100g of pure zinc powder as the quantitative basis for calculating the mass of β-TCP particles. Based on the volume ratio of pure zinc powder to β-TCP particles in the Zn@3β-TCP composite scaffold being 97:3, 1.36g of β-TCP particles should be added to 100g of pure zinc powder. The specific calculation is as follows:

[0025] in m Zn For 100g, ρ Zn It is 7.14 g / cm³ 3 , ρ β-TCP 3.14 g / cm 3 .

[0026] III. The following is a comparison of the molding quality of Zn@3β-TCP composite scaffolds under different laser process parameters: Using laser powder melting and forming technology, with a powder layer thickness of 0.02 mm and a laser scanning spacing of 0.04 mm, the process parameters were optimized by changing the laser power and laser scanning speed, as shown in Table 1 below.

[0027] Table 1

[0028] As shown in Table 1, the sample prepared under the process parameters of 40W laser power and 200mm / s laser scanning speed has the highest density (i.e., molding quality), reaching 97.27%. Therefore, the preferred process parameters are: 40W laser power, 200mm / s laser scanning speed, 0.04mm laser scanning spacing, and 0.02mm layer thickness.

[0029] IV. A preferred embodiment of the present invention provides a method for preparing a Zn@β-TCP composite material scaffold, comprising the following steps: (1) Ingredients and mixing Weigh the raw materials in a vacuum glove box, weighing 100g of zinc powder and 1.36g of β-TCP particles respectively. Place the weighed raw materials in a polytetrafluoroethylene vacuum ball mill jar, add agate balls, and the ball-to-material weight ratio is 2:1. Seal the ball mill jar, evacuate the ball mill jar to a vacuum, and then place it in a planetary ball mill for ball milling and mixing for 4 hours.

[0030] Mix approximately 5000g of powder using the same steps as above, and set aside.

[0031] (2) Structural design The nTopology software was used for topology design, creating 2.5×2.5×2.5mm sheet-like Gyroid unit cells, arranged in an array with a 10×10×10mm lattice network structure. The lattice wall thickness was set along a unidirectional gradient direction, ranging from 0.25 to 0.70 mm from left to right, corresponding to aperture sizes of 700–1100 μm. Figure 1 As shown, a gradient triple minimum surface (TPMS) structure model is constructed, and the model is exported as an STL format.

[0032] (3) Set process parameters and slice the model In the Magics software, select the BLT-S210 platform. After importing the model into the platform, set the printing parameters in the BLT-BP software: laser power 40W, laser scanning speed 200mm / s, laser scanning spacing 0.04mm, powder layer thickness 0.02mm, and a zigzag scanning path with a 67° rotation per layer. Finally, slice the model and import the sliced ​​model into the actual BLT-S210 printer for printing.

[0033] (4) Preparation of Zn@β-TCP composite scaffold by laser powder melting After cleaning the pure Zn substrate and rubber scraper with alcohol, install them in the equipment. Sift the mixed powder through a 200-mesh sieve and pour it into the powder loading tank, compacting it with an anti-static stainless steel spatula. Adjust the substrate height to be flush with the powder loading tank. Argon gas is used as a protective gas for purging; the argon pressure is set to 4 Pa. The fan is turned on when the oxygen content in the printing chamber is less than 0.5 ppm, and the substrate heating is turned on when the oxygen content is less than 0.3 ppm. Printing begins when the substrate is heated to 100°C and the oxygen content in the printing chamber is less than 0.01 ppm.

[0034] After printing is complete, wait for the substrate temperature to drop to room temperature, open the door, use an explosion-proof vacuum cleaner to remove excess powder from the substrate, then remove the substrate and use a wire cutting machine to cut the support sample from the substrate.

[0035] (5) Surface treatment Subsequent surface treatments were used to improve the surface quality of the scaffold. After printing, excess powder was removed from the holes using an explosion-proof vacuum cleaner. Sandblasting was then performed at 0.4 MPa to remove unmelted, adhered powder. Residual abrasive was removed using an air gun. The sandblasted samples were then placed in deionized water for ultrasonic cleaning and drying, resulting in a gradient porous Zn@β-TCP composite scaffold.

[0036] This invention utilizes laser powder melting technology to fabricate a Zn@β-TCP composite scaffold with a gradient porous structure, using Zn powder as the metal matrix and β-TCP particles as the ceramic particle reinforcement phase. By preheating the substrate and employing a low-power, low-scanning-speed printing strategy, the dispersion of β-TCP within the Zn matrix is ​​effectively improved. The addition of the β-TCP reinforcement phase enhances the scaffold's mechanical properties and accelerates its degradation rate. The gradient structure design provides greater space for osteoblast adhesion and proliferation, facilitating nutrient transport and bone tissue ingrowth.

[0037] V. Characterization, Testing, and Analysis In the preferred embodiment described above, the scaffold sample is a cube. Micro-CT characterization of the scaffold sample revealed that the actual pore diameter gradient of the prepared gradient porous Zn@β-TCP composite scaffold is approximately 673.84–1053.83 μm. Figure 2 As shown, it conforms to the preset pore diameter gradient range of 700±50μm~1100±50μm.

[0038] The degradation rate of a gradient porous Zn@β-TCP composite scaffold was tested in a simulated body fluid environment according to ASTM G31-72 standard. The simulated body fluid formulation consisted of 5.403±0.01g sodium chloride, 2.046±0.01g sodium bicarbonate, 2.046±0.01g sodium carbonate, 0.225±0.01g potassium chloride, 0.230±0.01g dipotassium hydrogen phosphate trihydrate, 0.311±0.01g magnesium chloride hexahydrate, 11.928±0.01g 4-hydroxyethylpiperazine ethanesulfonic acid, 0.293±0.01g calcium chloride, and 0.072±0.01g sodium sulfate dissolved in 1000mL of water. Figure 3 As shown in the figure, the degradation weight loss of the gradient porous Zn@β-TCP composite scaffold in simulated body fluid is shown. The figure shows the mass change and degradation rate of the scaffold during the 28-day degradation period. The degradation rate of the scaffold after 28 days of degradation is 5.73%.

[0039] According to ASTM E9-09 standard, a universal testing machine was used to conduct uniaxial compressive mechanics tests on a gradient porous Zn@β-TCP composite material scaffold, and the compressive yield strength and elastic modulus of the sample were obtained through compressive stress-strain curves. Figure 4 As shown, the compressive stress-strain curve of the gradient porous Zn@β-TCP composite scaffold is obtained by data fitting. The compressive yield strength and compressive elastic modulus of the scaffold are 39.15 MPa and 2.48 GPa, respectively.

[0040] This invention successfully prepared a gradient porous Zn@β-TCP composite scaffold with a three-circle minimal curved surface as the pore topology using laser melting forming technology. The pore diameter gradient range is 673.84~1053.83μm (preset range is 700±50μm~1100±50μm). The degradation rate of the scaffold after 28 days of degradation in a simulated body fluid environment is 5.73%. The compressive yield strength and compressive elastic modulus of the gradient porous Zn@β-TCP composite scaffold are 39.15MPa and 2.48GPa, respectively, which are between those of cortical bone and cancellous bone. It is a novel biodegradable bone repair material that can be applied to bone repair.

[0041] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the embodiments of the present invention have been described in detail, those skilled in the art should understand that modifications or equivalent substitutions to the technical solutions of the present invention do not depart from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of protection of the claims of the present invention.

Claims

1. A biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair, characterized in that: In the Zn@β-TCP composite material of the scaffold, the volume fraction of Zn is 95-99 vol.% and the volume fraction of β-TCP is 1-5 vol.%; the internal structure of the scaffold is a gradient porous structure.

2. The biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 1, characterized in that: The gradient porous structure uses a three-circle minimal surface as the pore topology, and the pore diameter linearly transitions from 700±50μm to 1100±50μm from the first layer to the last layer.

3. The biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 2, characterized in that: In the Zn@β-TCP composite material of the scaffold, the volume fraction of Zn is 97 vol.% and the volume fraction of β-TCP is 3 vol.%.

4. The biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 3, characterized in that: The support is a cube.

5. The method for preparing the biodegradable graded porous Zn@β-TCP composite scaffold for bone defect repair according to any one of claims 1 to 4, characterized in that: The steps include the following: Step (1), Ingredients and Mixing Weigh out the raw materials zinc powder and β-TCP particles, and ball mill them together to form a mixed powder. Step (2) Structural Design The nTopology software was used to design the topology structure, creating 2.5×2.5×2.5mm sheet-like Gyroid unit cells, which were arranged in an array with a 10×10×10mm lattice network structure. The lattice wall thickness was set along the unidirectional gradient direction, ranging from 0.25 to 0.70mm from left to right, corresponding to aperture sizes of 700±50μm to 1100±50μm. A three-circle minimal surface structure model was constructed, and the model was exported as an STL file. Step (3): Set process parameters and slice the model. In the Magics software, select the BLT-S210 platform, import the model into the platform, and then set the printing parameters in the BLT-BP software. The model is then segmented and sliced, and the segmented model is imported into the actual BLT-S210 device for printing. Step (4): Laser powder melting to prepare Zn@β-TCP composite scaffold The mixed powder is loaded into the powder tank of the BLT-S210 equipment for printing; After printing is complete, wait for the substrate temperature to drop to room temperature, open the door to remove the substrate, and take the support sample off the substrate. Step (5) Surface treatment After surface treatment, the scaffold sample was obtained as a gradient porous Zn@β-TCP composite material scaffold.

6. The method for preparing the biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 5, characterized in that: In step (3), the printing parameters are: laser power of 40W, laser scanning speed of 200mm / s, laser scanning spacing of 0.04mm, layer thickness of 0.02mm, and a zigzag scanning path with a rotation of 67° for each layer.

7. The method for preparing the biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 5, characterized in that: In step (4), before printing begins, argon is used as a protective gas for purging. The argon pressure is set to 4Pa. When the oxygen content in the printing chamber is less than 0.5ppm, the fan is turned on. When the oxygen content is less than 0.3ppm, the substrate heating is turned on. The substrate is heated to 100°C. Printing begins when the oxygen content in the printing chamber is less than 0.01ppm.

8. The method for preparing the biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 7, characterized in that: In step (4), the argon pressure is set to 4 Pa.

9. The method for preparing the biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 5, characterized in that: In step (5), the bracket sample is cleaned of excess powder in the holes with an explosion-proof vacuum cleaner, and the sandblasting machine pressure is set to 0.4MPa for sandblasting treatment to remove unmelted adhering powder on the surface. The residual sand on the surface is removed with an air gun. The sandblasted sample is placed in deionized water for ultrasonic cleaning and drying to obtain a gradient porous Zn@β-TCP composite material bracket.

10. The method for preparing the biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 5, characterized in that: In step (1), zinc powder and β-TCP particles are weighed and placed in a polytetrafluoroethylene vacuum ball mill jar, agate balls are placed in the jar, the ball-to-material ratio is 2:1, the ball mill jar is sealed and vacuumed, and then the powder is ball-milled for 4 hours.

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