Degradable gradient porous Zn@β-tcp composite scaffold for bone defect repair and preparation method thereof

Abstract

The application belongs to the technical field of metal powder processing, and discloses a degradable gradient porous Zn@beta-TCP composite material support for bone defect repair and a preparation method.The volume fraction of Zn and beta-TCP in the Zn@beta-TCP composite material of the support is preferably 97 vol.% and 3 vol.%; the internal structure of the support is a gradient porous structure, specifically a three-week minimal surface as a pore topological structure, and the pore diameter linearly transitions from 700±50 mu m to 1100±50 mu m.The preparation method is that a gradient porous support model is designed by computer-aided design, Zn is used as a metal matrix, beta-TCP is used as a reinforcing phase, and a Zn@beta-TCP composite material support with a gradient porous structure is prepared by using a laser powder melting technology.The gradient structure design in the prepared support can provide more space for the adhesion and proliferation of osteoblasts, and is beneficial to the transmission of nutrients and the ingrowth of bone tissue.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of metal powder processing, and relates to a composite support, which can be used for biomedical materials, in particular to a degradable gradient porous Zn@beta-TCP composite support for bone defect repair and a preparation method thereof. BACKGROUND

[0002] Bone defect is a common disease in orthopedics. Small size bone defects can be self-healed or treated by conventional fracture treatment methods. When the bone defect range reaches the "critical bone defect length", bone transplantation surgery is needed for repair. Compared with traditional bone defect repair materials such as polylactic acid, collagen and hydroxyapatite, degradable metals have more excellent mechanical properties and unique degradable properties, and have become a new type of bone defect repair material. Among them, zinc-based materials have a more suitable degradation rate compared with magnesium-based materials and iron-based materials, but lack certain osteogenic activity. As a kind of bioceramics, beta-tricalcium phosphate (beta-TCP) has good osteoinductive ability. Adding beta-TCP to zinc-based materials can not only improve osteogenic activity, but also regulate the degradation performance of the materials.

[0003] From the application point of view, the human body has a porous structure inside the skeleton, so designing zinc-based materials into a porous structure not only provides space for tissue growth, but also effectively reduces the stress shielding effect caused by material implantation. In addition, the structure, shape and size of the bone defect site are different, and the internal pore structure (including porosity, pore diameter, pore distribution and pore shape) of the skeleton at different sites also has great differences, so how to provide patients with bone defect repair materials with customizable macroscopic shape and adjustable internal pore structure is the key to clinical application. SUMMARY

[0004] Based on the above problems, the purpose of the application is to use pure zinc (Zn) metal powder and beta-tricalcium phosphate (beta-TCP) particles as raw materials, adopt ball milling mixing method to prepare mixed powder, and prepare Zn@beta-TCP composite support with specific gradient porous structure by laser powder melting forming technology. By changing the material composition and pore structure, the mechanical properties, degradation rate and osteogenic activity of the Zn@beta-TCP composite support are regulated to realize stable and reliable bone defect repair function.

[0005] The application is implemented by using the following technical solutions:

[0006] In a first aspect, the present application provides a degradable gradient porous Zn@β-TCP composite scaffold for repairing bone defects, wherein the Zn@β-TCP composite of the scaffold has a volume fraction of Zn of 95-99 vol.% and a volume fraction of β-TCP of 1-5 vol.%; and the internal structure of the scaffold is a gradient porous structure.

[0007] Further preferably, the gradient porous structure is a three-periodic minimal surface (TPMS) as a pore topological structure, and the pore diameter linearly transitions from 700±50 μm to 1100±50 μm from the first layer to the last layer.

[0008] Further preferably, the Zn@β-TCP composite of the scaffold has a volume fraction of Zn of 97 vol.% and a volume fraction of β-TCP of 3 vol.%.

[0009] In a second aspect, the present application provides a preparation method of a degradable gradient porous Zn@β-TCP composite scaffold for repairing bone defects, comprising the following steps:

[0010] Step (1), batching and mixing

[0011] The raw materials zinc powder and β-TCP particles are weighed and ball-milled to form a mixed powder;

[0012] Step (2), structure design

[0013] The nTopology software is used for topological structure design, a 2.5×2.5×2.5 mm sheet-shaped Gyroid unit cell is created, an array arrangement is formed with a 10×10×10 mm lattice network structure, the lattice wall thickness is set along the unidirectional gradient direction, the lattice wall thickness is set to 0.25-0.70 mm from left to right, corresponding to the pore size of 700±50 μm-1100±50 μm, and a three-periodic minimal surface structure model is constructed, and the model is exported as an STL. format;

[0014] Step (3), setting process parameters and model slicing

[0015] In the Magics software, the BLT-S210 platform is selected, the model is imported into the platform, the printing parameters are set in the BLT-BP software after the model is imported, and then the model is sliced, and the sliced model is imported into the actual BLT-S210 device for printing;

[0016] Step (4), laser powder melting to prepare a Zn@β-TCP composite scaffold

[0017] The mixed powder is loaded into the powder loading groove of the BLT-S210 device for printing;

[0018] After printing, when the substrate temperature drops to room temperature, open the cabin door and remove the substrate, and then remove the support sample from the substrate;

[0019] Step (5), surface treatment

[0020] Excess powder in the holes of the support sample is removed, sand blasting is performed to remove the unmelted and adhered powder on the surface, and then the residual sand on the surface is removed; after the sand blasting treatment, the sample support is placed in deionized water, ultrasonic cleaning is performed, drying is performed, and a gradient porous Zn@β-TCP composite material support is obtained.

[0021] Further preferably, in step (3), the printing parameters are: the laser power is 40 W, the laser scanning speed is 200 mm / s, the laser scanning interval is 0.04 mm, the layer thickness is 0.02 mm, and the zigzag scanning route is rotated by 67° per layer.

[0022] Further preferably, in step (4), before starting printing, the height of the substrate is adjusted to be flush with the height of the powder loading tank; argon is used as the protective gas for gas washing, the argon pressure is set to 4 Pa, the fan is started when the oxygen content in the printing cabin is less than 0.5 ppm; the substrate heating is started when the oxygen content in the printing cabin is less than 0.3 ppm, the substrate is heated to 100℃, and the printing is started when the oxygen content in the printing cabin is less than 0.01 ppm.

[0023] The present application prepares a gradient porous degradable Zn@β-TCP composite material support by computer-aided design of a gradient porous model, using Zn powder as a metal matrix and β-TCP particles as a reinforcing phase, and using a laser powder melting forming technology. In the laser powder melting forming process, too fast heating and cooling can cause insufficient dispersibility of β-TCP in the molten pool, which in turn affects the forming quality of the Zn@β-TCP composite material support. The present application effectively improves the dispersibility of β-TCP in the Zn matrix by preheating the substrate and using appropriate laser power and scanning speed, and solves the technical problem of difficulty in forming caused by too large a melting point difference between Zn and β-TCP in the laser powder melting forming process.

[0024] The gradient porous Zn@beta-TCP composite scaffold prepared in the application has good mechanical properties, a suitable degradation rate, a completely through pore structure, can provide sufficient space for the adhesion and proliferation of osteoblasts, and is beneficial to the transmission of nutrients and the growth of new bone tissue. The gradient porous structure of the Zn@beta-TCP composite scaffold can match the mechanical properties and growth rates of human cortical bone to bone trabecula, can avoid the bone nonunion phenomenon caused by the stress shielding effect, and can balance the local degradation rate of the material and the local bone growth rate. Through testing, the prepared Zn@beta-TCP composite scaffold has a density of more than 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 being soaked in a simulated body fluid for 28 days.

[0025] The application has reasonable design and good clinical application value. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 A preset model of the gradient porous Zn@beta-TCP composite scaffold is shown, wherein A is a whole diagram of the preset model, and B is a sectional view.

[0027] Figure 2 A molded sample of the gradient porous Zn@beta-TCP composite scaffold is shown, wherein A is a whole diagram of the molded sample, and B is a sectional view.

[0028] Figure 3 A weight loss graph of the degradation of the gradient porous Zn@beta-TCP composite scaffold in a simulated body fluid is shown.

[0029] Figure 4 A compressive stress-strain curve graph of the gradient porous Zn@beta-TCP composite scaffold is shown. DETAILED DESCRIPTION

[0030] The specific embodiments of the application will be described in detail below with reference to the accompanying drawings.

[0031] The degradable gradient porous Zn@beta-TCP composite scaffold for bone defect repair described in the embodiments of the application uses Zn powder as a metal matrix and beta-TCP particles as a ceramic particle reinforced phase. After mixing the powders, the Zn@beta-TCP composite scaffold with a gradient porous structure is prepared by computer-aided design and laser powder melting forming technology. The addition of the beta-TCP reinforced phase can not only improve the mechanical properties of the Zn matrix, but also accelerate the degradation of the scaffold. The completely through porous structure design can provide more space for the adhesion and proliferation of osteoblasts, is beneficial to the transmission of nutrients and the growth of bone tissue, and the gradient porous structure design can match the mechanical properties and growth rates of cortical bone to bone trabecula.

[0032] The chemical materials used in this embodiment are: zinc powder (powder diameter is between 15-53 μm), β-TCP particles (particle diameter is less than 200 nm), anhydrous ethanol, deionized water, sodium chloride, sodium bicarbonate, sodium carbonate, potassium chloride, potassium phosphate dibasic trihydrate, magnesium chloride hexahydrate, 4-hydroxyethyl piperazine ethanesulfonic acid, calcium chloride, sodium sulfate, chromium trioxide, graphite paper, sandpaper, argon. The amount of the chemical substances used is proportioned according to the pre-set amount, with gram (g), liter (L), milliliter (mL), millimeter (mm) and the like as the units of measurement.

[0033] The laser additive manufacturing equipment used in this embodiment is an existing laser powder bed fusion equipment with a model of BLT-S210, which is operated in sequence according to the operation requirements.

[0034] II. Comparison of mechanical strength of Zn@β-TCP composite scaffold with different volume fractions of β-TCP is as follows:

[0035] Under the same process parameters (same as the fourth part of the embodiment below), Zn@β-TCP composite scaffolds with different volume fractions of β-TCP (the volume fraction of Zn and β-TCP is 100 vol.%) are prepared by laser powder melting forming technology: Zn@1β-TCP (wherein 1 represents the volume fraction of β-TCP is 1 vol.%), Zn@3β-TCP (wherein 3 represents the volume fraction of β-TCP is 3 vol.%), Zn@5β-TCP (wherein 5 represents the volume fraction of β-TCP is vol.5%).

[0036] The compression mechanical property test of the above samples is carried out by using a universal mechanical testing machine, and the results are as follows: the yield strength of Zn@1β-TCP composite scaffold is 102.31 MPa, the yield strength of Zn@3β-TCP composite scaffold is 133.77 MPa, and the yield strength of Zn@5β-TCP composite scaffold is 119.76 MPa. From the above results, it can be known that when the volume fraction of β-TCP is 3%, the Zn@β-TCP composite scaffold exhibits the highest mechanical strength.

[0037] In specific implementation, the weighing and powder mixing of raw materials in the preparation process of Zn@β-TCP composite scaffold: the raw materials need to be weighed before powder mixing, and the weighing quality of β-TCP particles is calculated based on 100 g of pure zinc powder. According to the volume ratio of pure zinc powder to β-TCP particles in Zn@3β-TCP composite scaffold is 97:3, 1.36 g of β-TCP particles should be added to 100 g of pure zinc powder, and the specific calculation is as follows:

[0038]

[0039] wherein m Zn 100 g, p Zn 7.14 g / cm 3 , p β-TCP 3.14 g / cm 3 .

[0040] III. Comparison of forming quality of Zn@3β-TCP composite material scaffold under different laser process parameters is as follows:

[0041] Through the laser powder melting forming technology, under the conditions of powder layer thickness of 0.02 mm and laser scanning interval of 0.04 mm, the process parameters are optimized by changing the laser power and laser scanning speed, as shown in Table 1 below.

[0042] Table 1

[0043]

[0044] As can be seen from Table 1, the sample prepared under the process parameters of laser power of 40 W and laser scanning speed of 200 mm / s has the highest density (i.e. forming quality), reaching 97.27%. Therefore, the preferred process parameters are determined as follows: laser power 40 W, laser scanning speed 200 mm / s, laser scanning interval 0.04 mm, layer thickness 0.02 mm.

[0045] IV. The preferred embodiment of the application is a preparation method of a Zn@β-TCP composite material scaffold, comprising the following steps:

[0046] (1) batching and mixing

[0047] In a vacuum glove box, the raw materials are weighed, 100 g of zinc powder and 1.36 g of β-TCP particles are weighed respectively, and the weighed raw materials are placed in a polytetrafluoroethylene vacuum ball mill jar, maroon balls are placed, the ball-to-material weight ratio is 2:1, the ball mill jar is sealed, the ball mill jar is evacuated, and then placed in a planetary ball mill for ball milling and powder mixing for 4 hours.

[0048] About 5000 g of the blended powder is prepared as above for standby use.

[0049] (2) structure design

[0050] The nTopology software is used for topology structure design, a 2.5×2.5×2.5 mm sheet-shaped Gyroid unit cell is created, an array arrangement is formed with a 10×10×10 mm lattice network structure, the lattice wall thickness is set along the unidirectional gradient direction, and the lattice wall thickness is set to 0.25-0.70 mm from left to right, corresponding to the aperture size of 700-1100 μm, as shown inFigure 1 The model was constructed into a gradient triply periodic minimal surface (TPMS) structure model and exported as an STL format.

[0051] (3) Setting process parameters and model slicing

[0052] The BLT-S210 platform was selected in the Magics software. After the model was imported into the platform, the printing parameters were set in the BLT-BP software: the laser power was 40 W, the laser scanning speed was 200 mm / s, the laser scanning interval was 0.04 mm, the powder layer thickness was 0.02 mm, and the sawtooth scanning route was 67° per layer. Finally, the model was sliced, and the sliced model was imported into the actual BLT-S210 device for printing.

[0053] (4) Preparation of Zn@β-TCP composite scaffold by laser powder melting

[0054] The pure Zn substrate and rubber scraper were cleaned with alcohol and installed in the device. The mixed powder was sieved through a 200-mesh sieve and poured into the powder loading tank, and then stirred with an anti-static stainless steel fork. The substrate height was adjusted to be flush with the powder loading tank height. Argon was used as the protective gas for gas washing, and the argon pressure was set to 4 Pa. When the oxygen content in the printing cabin was less than 0.5 ppm, the fan was started, and when the oxygen content was less than 0.3 ppm, the substrate heating was started. The substrate was heated to 100°C, and the printing started when the oxygen content in the printing cabin was less than 0.01 ppm.

[0055] After printing, when the substrate temperature dropped to room temperature, the cabin door was opened, and the excess powder on the substrate was removed with an explosion-proof vacuum cleaner. The substrate was then removed, and the scaffold sample was cut from the substrate using a wire cutting machine.

[0056] (5) Surface treatment

[0057] The surface quality of the scaffold was improved by surface treatment. After printing, the scaffold sample was cleaned with an explosion-proof vacuum cleaner to remove excess powder from the holes. The sandblasting machine was set to a pressure of 0.4 MPa for sandblasting treatment to remove the unmelted and adhered powder on the surface. The gas gun was used to remove the residual sand on the surface. The sandblasted sample was placed in deionized water and ultrasonically cleaned, dried, and obtained a gradient porous Zn@β-TCP composite scaffold.

[0058] The embodiment of the application prepares a Zn@β-TCP composite scaffold with a gradient porous structure by a laser powder melting forming technology, taking Zn powder as a metal matrix and β-TCP particles as a ceramic particle reinforced phase. The dispersibility of β-TCP in the Zn matrix is effectively improved by preheating the substrate and setting a small power and low scanning speed printing strategy. The addition of the β-TCP reinforced phase improves the mechanical properties of the scaffold and accelerates the degradation rate. The gradient structure design provides more space for the adhesion and proliferation of osteoblasts, and is conducive to the transmission of nutrients and the growth of bone tissue.

[0059] V. Characterization, testing, analysis

[0060] In the above preferred embodiment, the scaffold sample is a cube, and the actual pore diameter gradient of the prepared gradient porous Zn@β-TCP composite scaffold is about 673.84-1053.83 μm, as shown in Figure 2 , which meets the preset pore diameter gradient range of 700±50 μm-1100±50 μm.

[0061] According to the ASTM G31-72 standard, the degradation rate of the gradient porous Zn@β-TCP composite scaffold in a simulated body fluid environment is tested. The simulated body fluid formula is 1000 mL of water dissolving 5.403±0.01 g of sodium chloride, 2.046±0.01 g of sodium bicarbonate, 2.046±0.01 g of sodium carbonate, 0.225±0.01 g of potassium chloride, 0.230±0.01 g of di-potassium hydrogen phosphate trihydrate, 0.311±0.01 g of magnesium chloride hexahydrate, 11.928±0.01 g of 4-hydroxyethyl piperazine ethanesulfonic acid, 0.293±0.01 g of calcium chloride, and 0.072±0.01 g of sodium sulfate. As shown in Figure 3 , the degradation weight loss graph of the gradient porous Zn@β-TCP composite scaffold in the simulated body fluid shows the mass change and degradation rate of the scaffold in a 28-day degradation period. The degradation rate of the scaffold after 28 days of degradation is 5.73%.

[0062] According to the ASTM E9-09 standard, a universal mechanical testing machine is used to perform uniaxial compression mechanical testing on the gradient porous Zn@β-TCP composite scaffold, and the compressive yield strength and elastic modulus of the sample are obtained through the compression stress-strain curve. As shown in Figure 4 , the compression stress-strain curve of the gradient porous Zn@β-TCP composite scaffold, the compression yield strength and compression elastic modulus of the scaffold are obtained through data fitting, which are 39.15 MPa and 2.48 GPa, respectively.

[0063] The application successfully prepares a gradient porous Zn@beta-TCP composite scaffold with a three-pole small curved surface as a pore topological structure by a laser melting forming technology, the pore diameter gradient range of the scaffold is 673.84-1053.83 mu m (the preset range is 700+ / -50 mu m-1100+ / -50 mu m); the degradation rate of the scaffold after degradation in a simulated body fluid environment for 28 days is 5.73%; the compression yield strength and the compression elastic modulus of the gradient porous Zn@beta-TCP composite scaffold are 39.15 MPa and 2.48 GPa respectively, which are between cortical bone and cancellous bone, and the gradient porous Zn@beta-TCP composite scaffold is a new degradable bone repair material which can be applied to bone repair.

[0064] Finally, it should be explained that the above examples are only used to illustrate the technical solutions of the application and are not limited. Although the technical solutions of the application are described in detail with reference to the examples, those skilled in the art should understand that the technical solutions of the application can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the application, and they should be covered in the protection scope of the claims of the application.

Claims

1. A method for preparing a biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair, characterized in that: Includes the following steps: Step (1), Ingredients and Mixing Weigh zinc powder and β-TCP particles and place them in a polytetrafluoroethylene vacuum ball mill jar. Add agate balls with a ball-to-material ratio of 2:

1. Seal the ball mill jar and evacuate it to a vacuum. Then, ball mill the powder for 4 hours 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. 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 67° rotation per layer. Step (4): Laser powder melting to prepare Zn@β-TCP composite material scaffold. The mixed powder is loaded into the powder loading tank of the BLT-S210 equipment for printing; 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. When the substrate is heated to 100℃ and the oxygen content in the printing chamber is less than 0.01ppm, printing begins. 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.

2. The method for preparing the biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 1, 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.

3. A biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair, prepared using the method for preparing a biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair as described in claim 1 or 2, 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. 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.

4. The biodegradable gradient porous Zn@β-TCP composite scaffold for bone defect repair according to claim 3, 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.%.

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

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