A method for preparing a bioceramic bone scaffold with gradient structure using 3DFP additive manufacturing

Abstract

The application discloses a preparation method of a bioceramic bone scaffold with a gradient structure using 3DFP additive manufacturing; the method comprises the following steps: designing a biological gradient structure model; preparing a wire material containing nano-zirconium oxide, tricalcium phosphate, hydroxyapatite and silver oxide powder, mixing and preparing a slurry, and preparing a wire; adding the prepared wire into a printer, completing layer-by-layer printing of the gradient structure according to a slicing path, and obtaining a scaffold body; and heat treating, then cooling in a furnace to room temperature, thereby obtaining the bioceramic bone scaffold. The composition ratio of the wire material is optimized in a deep level, and the mechanical strength of the scaffold material is improved; meanwhile, the composition gradient and the structure gradient are designed, the cancellous bone with different components and structures is designed in the inner layer on the basis of guaranteeing the high strength, hardness and bending resistance of the compact bone, so that the scaffold and the tissue or cells can effectively interact, the adhesion, proliferation and differentiation of the bone cells are promoted, and the tissue repair and regeneration are facilitated.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of additive manufacturing and bionic structure design, and particularly relates to a method for preparing a bioceramic bone scaffold with a gradient structure by using 3DFP additive manufacturing. BACKGROUND

[0002] Repair and regeneration of bone tissue is an important problem in the biomedical field. With the increase of population aging and diseases, the problem of bone defect repair has become a global challenge. Traditional bone scaffolds have many limitations in promoting bone tissue growth, such as low mechanical properties, insufficient bioactivity, etc.

[0003] (1) Poor mechanical strength: the prior art uses collagen, alginate, gelatin or high molecular polymer to manufacture a biological scaffold material, but the compression strength, bending strength, rigidity and adjustability are poor. Since the biological scaffold needs to bear various mechanical loads in the human body, such as stress, extrusion, shear and the like, for example, the bone scaffold will bear muscle tension and pressure from the surrounding tissue, and the aforementioned scaffold material cannot meet the use requirements.

[0004] (2) Insufficient biodegradation performance and activity: natural materials such as gelatin, alginate, gelatin or high molecular polymer may have adverse reactions; and the biodegradation performance and activity are insufficient.

[0005] (3) Difficulty in forming complex scaffold structure, long development cycle: traditional sintering method, gel injection molding, grouting molding and direct solidification injection molding scaffold structure need to go through multiple steps such as mold design, manufacturing, assembly, etc. The preparation process is relatively slow, and a long preparation time is required, the material utilization rate is low, and it is difficult to carry out personalized customization, and it is difficult to realize the manufacturing of multifunctional complex structure. Even if the existing mainstream biological scaffold additive manufacturing technology such as slurry extrusion molding and fused deposition molding is used, there are some deficiencies. The extrusion type molding additive manufacturing is difficult to realize the manufacturing of large size pores of the scaffold material, especially difficult to form a scaffold with a spacing greater than 1mm. Fused deposition molding is limited by the selection of wire materials, and it is more inclined to manufacture thermoplastic materials such as wax, ABS, nylon, etc.

[0006] Bioceramic materials are widely used in bone defect repair field due to their excellent biocompatibility, bioactivity and mechanical properties. Therefore, it is of great practical significance and application value to research and develop a bioceramic bone scaffold with excellent mechanical properties and bioactivity.

[0007] Through the search of the existing patent documents, CN200310122687.8 discloses a nano-zirconium oxide strong toughening high porosity calcium phosphate artificial bone scaffold and a preparation method thereof; it is made by mixing nano-zirconium oxide and hydroxyapatite in a proper ratio to form a slurry, and then coating the slurry on a polyurethane sponge with a proper pore size and porosity and sintering. Due to the high porosity and proper pore size, not only is the β-calcium phosphate easy to be degraded and absorbed, but also the bone tissue is easy to grow into and fuse at a fast speed, and the scaffold is firmly combined with the host bone without obvious foreign body reaction. However, the scaffold with uniform structure cannot meet the needs of medical artificial bone, and there is a big gap from the gradient porosity structure of natural bone. The present application can realize flexible regulation and control of the gradient distribution of the scaffold structure, realize the hierarchy and function of natural bone tissue, provide different mechanical properties and chemical composition support in different regions, thereby enhancing the overall mechanical properties of the repaired bone and improving the biological activity, biological adaptability and antibacterial performance, so that it is closer to natural bone tissue.

[0008] CN201510194743.1 discloses an additive manufacturing method of a multi-scale biomimetic artificial bone scaffold. After mixing a biopolymer material and a bioceramic material, the mixture is mixed with deionized water or an organic solvent to form a uniform slurry, and then freeze-dried to obtain a homogeneous powder. The powder is mixed with deionized water or an organic solvent and stirred, vacuumed, and then quantitatively extruded by a screw pump. An XYZ motion device is used to complete the additive manufacturing according to a three-dimensional geometric model of a bone defect obtained by CT scanning, and the pore shape, size and porosity inside the geometric model are designed by a computer program, and the motion trajectory of the extruded material is completed. The additive manufacturing method uses degradable biological composite materials, and the bone defect site is eventually replaced by the body's own tissue, meeting the body's lifelong growth requirements. The method directly uses a screw pump to quantitatively extrude the required biological material, and the amount is accurately controllable, and the clinical application cost of artificial bone is significantly reduced. The method has the advantages of accurate printing material amount, wide material application range, accurate adjustable pore structure, and free forming of macroscopic geometric shape. However, the technology described in the patent fails to achieve effective post-processing of the printed scaffold, making it difficult to meet the requirements in terms of mechanics and other properties. In the biological activity, the skeleton and joints are affected by various forces and pressures, which are transmitted to the biological scaffold. If the strength and toughness of the scaffold are insufficient, deformation, fracture and other problems may occur. The present application not only realizes the reasonable post-processing of the gradient structure scaffold and improves the physical bearing capacity of the structure, but also realizes the flexible balance regulation and control of the biological activity, mechanical properties and antibacterial performance through the transition design of the chemical composition, which is of great significance for the scaffold to promote the maintenance of normal physiological functions and tissue repair of the organism. SUMMARY

[0009] The present application aims to solve the problems existing in the prior art, and provides a preparation method of a bioceramic bone scaffold with a gradient structure using 3DFP additive manufacturing (3DFP (3D Filament Printing) is different from FDM (Fused Deposition Modeling), a new type of additive manufacturing technology). The 3DFP printing technology designed in the present application can manufacture a scaffold in a shorter time, is more flexible and efficient, and can design and manufacture a scaffold with a complex shape and high personalization according to needs. In terms of mechanical strength, the prepared Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold has high compressive strength and bending strength, can bear a certain compression and bending load, and at the same time has moderate rigidity, which can provide sufficient support force and will not be too rigid to affect bone healing. Most importantly, the mechanical properties of the Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold can be flexibly optimized by adjusting parameters such as porosity and particle size to meet different biomechanical requirements. And after the addition of Ag2O with a lower decomposition temperature, silver ions form silver atoms due to their strong negative charge, and oxygen ions form oxygen gas and escape, so there are more oxygen vacancies in the scaffold. The existence of a large number of oxygen vacancies is beneficial to the formation of a more dense structure of the material, thereby synergistically improving the mechanical properties of the scaffold, while also having excellent antibacterial properties. In terms of biodegradation and activity, the prepared Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold is a biodegradable artificial bone scaffold, which can be decomposed by enzymes in the body and gradually absorbed, and finally metabolized into harmless substances; at the same time, the Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold has good biological activity, can promote the growth of bone cells and bone tissue regeneration, and is helpful to accelerate bone healing, while also having good antibacterial properties.

[0010] Specifically, the purpose of the present application is achieved by the following technical solutions:

[0011] The present application provides a preparation method of a bioceramic bone scaffold with a gradient structure, which comprises the following steps:

[0012] S1, designing a biological gradient structure model with different porosities, and performing three-dimensional modeling;

[0013] S2, preparing a filament material, mixing and preparing a slurry, and preparing a filament; the filament material comprises nano-zirconium oxide, tricalcium phosphate, hydroxyapatite and silver oxide powder;

[0014] S3, adding the prepared filament to a printer, and completing layer-by-layer printing of the gradient structure according to a preset printing strategy and printing scheme according to a slicing path, to obtain a gradient bioceramic scaffold blank;

[0015] S4, heat treating the gradient bioceramic scaffold blank, and then furnace cooling to room temperature to obtain the bioceramic bone scaffold.

[0016] As an embodiment of the present application, in step S1, the biological gradient structure comprises a structural gradient, and the outer layer is compact bone and the inner layer is cancellous bone.

[0017] As an embodiment of the present application, in step S1, a biological structure model is established, and geometric simplification and processing are performed, and a gradient structure with a scaffold gap of 1.5-0.25 mm is designed on the cross section.

[0018] As an embodiment of the present application, the gradient change is an equal gradient change.

[0019] In some embodiments, the pore structure of the scaffold is designed according to an equal gradient change, and contains five pore transition regions, i.e., the pore on one side is 1.5 mm, gradually changes to 1.25 mm, 1 mm, 0.75 mm, 0.5 mm, and 0.25 mm from one side to the other side.

[0020] As an embodiment of the present application, in step S1, the biological gradient structure comprises a component gradient, and the material components of the outer layer and the inner layer of the bone scaffold are different.

[0021] As an embodiment of the present application, in step S2, a 3DFP additive manufacturing method is used.

[0022] As an embodiment of the present application, in step S2, the outer layer of the bone scaffold comprises a powder combination 1: Nano-ZrO2: 72-85%, HA: 12-18%, TCP: 2-6%, and Ag2O: 1-4%.

[0023] As an embodiment of the present application, in step S2, the inner layer comprises a powder combination 2: Nano-ZrO2: 72-85%, HA: 2-6%, TCP: 12-18%, and Ag2O: 1-4%.

[0024] As an embodiment of the present application, the outer layer and the inner layer of the scaffold both further comprise a binder with a mass ratio of 55-47%.

[0025] As an embodiment of the present application, the binder comprises: PLA 50-70%, SA 8-10%, and PW 20-40%.

[0026] As an embodiment of the present application, in step S3, the printing process is set to a fill density of 85-93%, a wall thickness of 0.8-1.2 mm, a layer height of 0.8-1.2 mm, and a printing speed of 50-65 mm / min. In some embodiments, the printing process is set to a fill density of 90%, a wall thickness of 1.0 mm, a layer height of 1 mm, and a printing speed of 60 mm / min.

[0027] As an embodiment of the present application, the heat treatment further comprises a step of placing the printed scaffold blank in a drying oven at a temperature of 50-65℃ and a humidity of less than 8-12% for 20-28 hours before the heat treatment. In some embodiments, the printed scaffold blank is placed in a drying oven at a temperature of 60℃ and a humidity of less than 10% for 24 hours.

[0028] As an embodiment of the present application, the heat treatment has a heating rate of 1-3℃ / min, a treatment temperature of 1150-1550℃, and a holding time of 1.5-2.5 hours.

[0029] The gradient-structured bioceramic bone scaffold prepared by the foregoing method also falls within the protection scope of the present application.

[0030] Compared with the prior art, the present application has the following beneficial effects:

[0031] (1) Optimizing mechanical strength: In view of the poor mechanical strength of the biological scaffold material, the proportions of nano-zirconium oxide, hydroxyapatite, tricalcium phosphate, and silver oxide are optimized in depth to improve the mechanical strength of the scaffold material. At the same time, the composition gradient and structure gradient double design concepts are used to simulate the solid bone: on the basis of ensuring the high strength, hardness, and bending resistance of the compact bone, the inner layer is designed to be different from the cancellous bone in composition and structure, thereby ensuring the effective interaction between the scaffold and the tissue or cells, promoting the adhesion, proliferation, and differentiation of bone cells, and being helpful for tissue repair and regeneration.

[0032] (2) Improving biodegradation performance and activity: In view of the insufficient biodegradation performance and activity of the scaffold material, the content and surface properties of nano-zirconium oxide and the like are adjusted to precisely control the biodegradation performance and activity: on the one hand, the surface reactivity of the scaffold material is improved, so that it is more easily decomposed by the hydrolytic enzyme in the body, and the surface of the chemically modified nano-particles with positive charge is more easily adsorbed to the cell surface, thereby promoting the adhesion and proliferation of cells and accelerating the degradation of the scaffold material; on the other hand, the surface roughness, chemical functional groups, surface energy, and micro-porosity of the scaffold are balanced to obtain higher frequency of cell adhesion and proliferation opportunities, and the biological activity of the scaffold is greatly improved.

[0033] (3) Shorten the development cycle: For the problem of complex scaffold structure forming difficulty, long development cycle, 3DFP printing technology can effectively solve these problems, improve the preparation efficiency and quality of complex biological scaffold structure. When using 3DFP printing, optimize the printing speed, extrusion speed, layer height and other printing parameters, adjust and design through slurry formula, printing strategy, post-processing scheme and other aspects to meet different clinical needs and application scenarios, while having good customizability and plasticity, greatly shorten the development cycle. BRIEF DESCRIPTION OF DRAWINGS

[0034] Other features, objects, and advantages of the application will become more apparent from the following detailed description of non-limiting embodiments, when read in conjunction with the accompanying drawings:

[0035] Figure 1 Preparation process flow chart of biological ceramic bone scaffold with gradient structure using 3DFP additive manufacturing;

[0036] Figure 2 Preparation process schematic diagram of biological ceramic bone scaffold with gradient structure using 3DFP additive manufacturing;

[0037] Figure 3 Local structure top view and side view of biological ceramic bone scaffold with gradient structure using 3DFP additive manufacturing. DETAILED DESCRIPTION

[0038] The application will be described in detail below with reference to examples. The following examples will help those skilled in the art to further understand the application, but do not limit the application in any form. It should be noted that for those skilled in the art, without departing from the concept of the present application, a number of adjustments and improvements can be made. These are within the scope of protection of the present application. The experimental methods used in the following examples are conventional methods unless otherwise specified.

[0039] Example 1

[0040] This embodiment relates to a method for manufacturing a biological ceramic bone scaffold with a double-layer gradient structure, including gradient structure design, slurry composition, printing strategy development, printing parameter setting, post-processing scheme, etc. Figure 1 As shown in:

[0041] Gradient structure design: design a biological gradient structure model with different porosities, and perform three-dimensional modeling. The biological scaffold gradient structure refers to the realization of certain chemical and geometric gradient distribution in the scaffold structure to simulate the tissue structure and function in vivo. Using three-dimensional modeling software can help designers design and optimize biological scaffold gradient structures more accurately and efficiently. With the help of CT or MRI scan images, biological structure models are established, and geometric simplification and processing are performed. The gradient structure with different porosities (1.5-0.25mm gradient change) is designed on the cross section. Specifically, the pore structure design of the scaffold in this embodiment follows the equal gradient change, and contains 5 pore transition regions, i.e. the pore on one side is 1.5mm, gradually changes to 1.25mm, 1mm, 0.75mm, 0.5mm and 0.25mm from one side to the other side. The pore composition design of the scaffold is divided into inner and outer layers, and contains 1 composition transition region, i.e. one side is formula 1 and the other side is formula 2. Specifically, as shown in Figure 2 the gradient biological scaffold is designed first, the.stl file is generated for slicing, then the prepared filament raw material containing different component proportions is extruded and heated from the nozzle through the extrusion and heating mechanism, and the gradient scaffold is realized by additive manufacturing on the building platform.

[0042] Silk composition configuration: equipped with silk raw materials with different proportions, the silk raw materials include nano zirconium oxide, tricalcium phosphate, hydroxyapatite and silver oxide powder. The steps of slurry configuration include the following aspects: preparation of materials, weighing of materials, mixing and stirring.

[0043] (1) Preparation and weighing of materials: Nano-zirconia powder, tricalcium phosphate powder, hydroxyapatite powder, silver oxide powder are used as the scaffold matrix, and various powders are weighed according to the formula proportion. Two formula proportions are involved in the present application: ① Nano-ZrO2: 70-85%, HA: 12-18%, TCP: 2-6%, Ag2O: 1-4%, ② Nano-ZrO2: 70-85%, HA: 2-6%, TCP: 12-18%, Ag2O: 1-4%, the weighed powder is put into a dry container. The specified formula powder is mixed and stirred uniformly using a stirrer, the stirring time is 2h, and it is ensured that all ingredients are fully mixed. The powder is added to the PLA (polylactic acid), SA (stearic acid), PW (paraffin) mixture (PLA: 50-70%, SA: 8-10%, PW: 20-40%) through an extruder to form a wire for standby use; wherein the loading mass ratio of powder to mixture is powder: 45-53%, mixture: 55-47%. In this embodiment, the powder formula ① proportion is Nano-ZrO2: 76%, HA: 16%, TCP: 5%, Ag2O: 3%, ② Nano-ZrO2: 83%, HA: 4%, TCP: 12%, Ag2O: 3%. The mixture ratio is: PLA: 60%, SA: 10%, PW: 30%. The mass ratio of powder to mixture is: powder: 48%, mixture: 52%.

[0044] Print strategy: Develop a print strategy and print plan to complete the layer-by-layer printing of the gradient structure according to the slicing path. The printing process is set to a fill density of 90% to ensure that the scaffold structure is tight and provides sufficient strength and stability. The wall thickness is set to 1.0mm to increase the overall strength and durability of the scaffold and ensure the tightness of the external structure. The layer height is set to 1mm, and the printing speed is 60mm / min to obtain high resolution and surface quality. The prepared wire is added to the printer, and the bioceramic scaffold is manufactured according to the above printing strategy and plan. As Figure 2 , the specific process is: the wire raw material is added to the 3DFP printer containing Z-axis column, build platform and wire heating device, the wire is melted and extruded through the printing nozzle after being heated, and the layer-by-layer manufacturing of the blank is completed by the Z-axis column mechanical device on the build platform, when the printing reaches the position of the composition and structure gradient design, the structure and composition gradient of the blank are flexibly adjusted by switching the wire above the extruder.

[0045] Post-processing scheme: after the gradient bioceramic scaffold blank is manufactured, the printed blank is post-processed: the heating rate is 1-3°C / min, the processing temperature is 1150-1550°C, the holding time is 1.5-2.5 hours, and then the furnace is cooled to room temperature. In this embodiment, the printed blank scaffold is placed in a dry oven with a temperature of 60°C and a humidity of less than 10% for 24 hours to remove moisture from the material. The dried scaffold is heat treated at a heating rate of 1.5°C / min. When the temperature rises to 1350°C, the holding time is 2.5 hours, the binder is burned out, and the strength of the scaffold is improved, and then the furnace is cooled.

[0046] The bioceramic scaffold prepared by the process has an external tightness, high strength, internal looseness, and strong bioactivity with a gradient arrangement, as shown in Figure 3 The scaffold has a designed structural gradient structure in the horizontal direction indicated by the arrow, the dense pore position is formula 1 component, the loose pore position is formula 2 component, and the scaffold has good interconnectivity. According to GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the performance test results show that the scaffold can obtain a maximum compression strength of 16.2 MPa, a hardness of 513 HV, a porosity of up to 65%, a shrinkage rate of less than 10%, and a MRSA experiment result of 75 CFU, which indicates that the scaffold maintains good bioactivity and antibacterial performance. The gradient bioceramic scaffold prepared by the preparation method not only ensures the effective transport of nutrients and cell growth in the artificial bone scaffold, but also improves the overall carrying capacity and antibacterial performance. Unlike traditional mold forming methods, this preparation method can be customized according to individual differences of patients, greatly shortening the production cycle of bioceramic scaffolds.

[0047] Example 2

[0048] The design of the gradient structure is the same as that of Example 1.

[0049] Composition of the wire material: equipped with wire raw materials with different proportions, the wire raw materials include nano-zirconium oxide, tricalcium phosphate, hydroxyapatite, and silver oxide powder. The steps of slurry preparation include the following aspects: preparing materials, weighing materials, mixing, and stirring.

[0050] (1) Preparation and weighing of materials: Nano-zirconia powder, tricalcium phosphate powder, hydroxyapatite powder, silver oxide powder are used as the scaffold matrix, and various powders are weighed according to the formula proportion. The formula ① proportion is Nano-ZrO2: 83%, HA: 13%, TCP: 3%, Ag2O: 1%, ② Nano-ZrO2: 75%, HA: 6%, TCP: 18%, Ag2O: 1%. The mixture proportion is: PLA: 50%, SA: 10%, PW: 40%. The mass proportion of powder and mixture is: powder: 52%, mixture: 48%.

[0051] Printing strategy: same as example 1.

[0052] Post-processing scheme: after the gradient bioceramic scaffold blank is manufactured, the printed blank scaffold is placed in a dry oven with a temperature of 60°C and a humidity of less than 10% for 24h to remove moisture from the material. The dried scaffold is heat treated at a heating rate of 2.5°C / min, and when the temperature rises to 1500°C, it is kept for 2 hours to burn off the binder and improve the strength of the scaffold, and then cooled with the furnace.

[0053] According to GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the results show that the bioceramic scaffold can obtain a maximum compressive strength of 22.3MPa, the hardness is maintained at 601HV, the porosity can be realized at a maximum of 76%, the shrinkage rate is less than 10%, and through the XRD spectrum statistics of each phase half peak width, it is known that HA and TCP produce lower crystallinity, and through the analysis results of the scaffold immersed in SBF simulated body fluid, it is known that more apatite is attached to the surface of the scaffold, and through the MRSA experimental results, the scaffold antibacterial property is 120CFU, which shows that the scaffold maintains good biological activity and antibacterial performance. The gradient bioceramic scaffold prepared by the preparation method not only ensures the effective transport of nutrients and cell growth in the artificial bone scaffold, but also improves the overall carrying capacity. Unlike traditional mold forming methods, this preparation method can be customized according to individual differences of patients, greatly shortening the production cycle of bioceramic scaffolds.

[0054] Example 3

[0055] Design of gradient structure: same as example 1.

[0056] Composition of wire material: equipped with wire raw materials with different proportions, the wire raw materials include nano-zirconia, tricalcium phosphate, hydroxyapatite, and silver oxide powder. The steps of slurry preparation include the following aspects: preparation of materials, weighing of materials, mixing and stirring.

[0057] (1) Preparation and weighing of materials: Nano-zirconium oxide powder, tricalcium phosphate powder, hydroxyapatite powder, silver oxide powder are used as the scaffold matrix, and various powders are weighed according to the formula proportion. Formula ① proportion: Nano-ZrO2: 72%, HA: 18%, TCP: 6%, Ag2O: 4%, ② Nano-ZrO2: 80%, HA: 2%, TCP: 14%, Ag2O: 4%. The mixture ratio is: PLA: 72%, SA: 8%, PW: 20%. The mass ratio of powder and mixture is: powder: 50%, mixture: 50%.

[0058] Printing strategy: same as example 1.

[0059] Post-processing scheme: after the gradient bioceramic scaffold blank is manufactured, the printed blank scaffold is placed in a dry oven with a temperature of 60°C and a humidity of less than 10% for 24h to remove moisture from the material. After drying, the scaffold is heat treated at a heating rate of 1°C / min, and when the temperature rises to 1150°C, it is kept for 2 hours to burn off the binder and improve the strength of the scaffold, and then cooled with the furnace.

[0060] According to the standards of GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the performance test results show that the bioceramic scaffold can obtain a maximum compressive strength of 11.5MPa, a hardness of 400HV, a porosity of up to 64%, a shrinkage rate of less than 10%, and through XRD spectrum statistics of each phase half-peak width, it can be known that HA and TCP produce lower crystallinity, and through the analysis results of the scaffold immersed in SBF simulated body fluid, it can be known that more apatite is attached to the surface of the scaffold, and through the MRSA experimental results, the scaffold antibacterial property is 60CFU, which shows that the scaffold maintains good biological activity and antibacterial performance. The gradient bioceramic scaffold prepared by the preparation method not only ensures the effective transport of nutrients and cell growth inside the artificial bone scaffold, but also improves the overall carrying capacity and antibacterial performance. The gradient bioceramic scaffold prepared by the preparation method not only ensures the effective transport of nutrients and cell growth inside the artificial bone scaffold, but also improves the overall carrying capacity. Unlike traditional mold forming methods, this preparation method can be customized according to individual differences of patients, greatly shortening the production cycle of bioceramic scaffolds.

[0061] Comparative example 1

[0062] In this comparative example, the design of the gradient structure, the formulation of the printing strategy, and the post-processing scheme are the same as example 3; the difference is that:

[0063] In the component configuration of the wire material, nano-zirconium oxide powder, tricalcium phosphate powder, and hydroxyapatite powder are used as the scaffold matrix, and various powders are weighed according to the formula proportion. Formula ① proportion: Nano-ZrO2: 76%, HA: 18%, TCP: 6%; Formula ② Nano-ZrO2: 84%, HA: 2%, TCP: 14%. The mixture proportion is: PLA: 72%, SA: 8%, PW: 20%. The mass proportion of the powder and the mixture is: powder: 50%, mixture: 50%.

[0064] According to the performance test standards of GB / T 1964-1996, GB / T 16534-2009, and GB / T 1966-1996, the results show that the bioceramic scaffold can obtain a maximum compressive strength of 7.2 MPa, a hardness of 308 HV, a porosity of up to 79%, and a shrinkage rate of less than 10%. At the same time, through the XRD spectrum statistics of each phase half-peak width, it can be known that HA and TCP produce lower crystallinity. At the same time, through the analysis results of the scaffold immersed in SBF simulated body fluid, it can be known that more apatite is attached to the surface of the scaffold. Through the MRSA experimental results, it can be known that the scaffold antibacterial property is 215 CFU, which indicates that the scaffold maintains good biological activity, but the antibacterial performance is poor.

[0065] Comparative Example 2

[0066] In this comparative example, the design of the gradient structure, the formulation of the printing strategy, and the post-processing scheme are the same as those of Example 3; the difference lies in that:

[0067] In the component configuration of the wire material, nano-zirconium oxide powder, tricalcium phosphate powder, and hydroxyapatite powder are used as the scaffold matrix, and various powders are weighed according to the formula proportion. Formula ① proportion: HA: 100%; Formula ② Nano-ZrO2: 50%, HA: 50%. The mixture proportion is: PLA: 72%, SA: 8%, PW: 20%. The mass proportion of the powder and the mixture is: powder: 50%, mixture: 50%.

[0068] According to the performance test standards of GB / T 1964-1996, GB / T 16534-2009, and GB / T 1966-1996, the results show that the bioceramic scaffold can obtain a maximum compressive strength of 1.02 MPa, a hardness of 172 HV, a porosity of up to 78%, and a shrinkage rate of less than 10%. At the same time, through the XRD spectrum statistics of each phase half-peak width, it can be known that HA and TCP produce lower crystallinity. At the same time, through the analysis results of the scaffold immersed in SBF simulated body fluid, it can be known that more apatite is attached to the surface of the scaffold. Through the MRSA experimental results, it can be known that the scaffold antibacterial property is 223 CFU, which indicates that the scaffold maintains very good biological activity, but the antibacterial performance and mechanical properties are poor.

[0069] Comparative Example 3

[0070] The gradient structure design, post-processing scheme in the present comparative example are the same as those in Example 3; the difference lies in that:

[0071] In the component configuration of the wire material, nano-zirconium oxide powder, tricalcium phosphate powder, hydroxyapatite powder, silver oxide powder are used as the scaffold matrix, and various powders are weighed according to the formula proportion. The formula proportion is Nano-ZrO2: 78%, HA: 10%, TCP: 10%, Ag2O: 2%. The mixture proportion is: PLA: 72%, SA: 8%, PW: 20%. The mass proportion of powder and mixture is: powder: 50%, mixture: 50%.

[0072] Printing strategy: develop printing strategy and printing scheme, complete layer-by-layer printing of gradient structure according to slicing path. The printing process is set to a filling density of 90% to ensure the tightness of the scaffold structure and provide sufficient strength and stability. The wall thickness is set to 1.0 mm to increase the overall strength and durability of the scaffold and ensure the tightness of the external structure. The layer height is set to 1 mm, and the printing speed is 60 mm / min to obtain high resolution and surface quality. The prepared wire material is added to the printer, and the above printing strategy and scheme are followed to manufacture the bioceramic scaffold. When the printing is carried out to the structure gradient design position, the flexible regulation of the green body structure and composition gradient is realized by switching the wire material above the extruder.

[0073] According to the standards of GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the performance test results show that the bioceramic scaffold can obtain a maximum compressive strength of 3.65 MPa, a hardness of 241 HV, a porosity of up to 73%, a shrinkage rate of less than 10%, and the XRD pattern statistics of each phase half-peak width shows that HA and TCP have lower crystallinity. The results of the scaffold immersed in SBF simulated body fluid show that more apatite is attached to the surface of the scaffold. The MRSA experimental results show that the scaffold antibacterial property is 95 CFU, which indicates that the scaffold maintains good biological activity and antibacterial performance.

[0074] Comparative Example 4

[0075] The gradient structure design, printing strategy development, post-processing scheme in the present comparative example are the same as those in Example 3; the difference lies in that:

[0076] The component configuration of the wire material is as follows: formula ① Nano-ZrO2: 60%, HA: 30%, TCP: 6%, Ag2O: 4%; formula ② Nano-ZrO2: 80%, HA: 2%, TCP: 14%, Ag2O: 4%. The mixture ratio is as follows: PLA: 72%, SA: 8%, PW: 20%. The mass ratio of the powder and the mixture is as follows: powder: 50%, mixture: 50%.

[0077] According to the performance test standards of GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the results show that the bioceramic scaffold can obtain a maximum compression strength of 7.4 MPa, a hardness of 301 HV, a maximum porosity of 77%, and a shrinkage rate of less than 10%. The half-peak width of each phase can be obtained by XRD spectrum statistics, and it is known that HA and TCP have a low crystallinity. The results of the scaffold immersed in SBF simulation body fluid show that more apatite is attached to the surface of the scaffold. The MRSA experimental results show that the antibacterial property of the scaffold is 65 CFU, which indicates that the scaffold maintains good biological activity and antibacterial performance.

[0078] Comparative Example 5

[0079] In the present comparative example, the design of the gradient structure, the formulation of the printing strategy, and the post-processing scheme are the same as those in Example 3; the difference lies in that:

[0080] The component configuration of the wire material is as follows: formula ① Nano-ZrO2: 72%, HA: 18%, TCP: 6%, Ag2O: 4%; formula ② Nano-ZrO2: 90%, HA: 2%, TCP: 4%, Ag2O: 4%. The mixture ratio is as follows: PLA: 72%, SA: 8%, PW: 20%. The mass ratio of the powder and the mixture is as follows: powder: 50%, mixture: 50%.

[0081] According to the performance test standards of GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the results show that the bioceramic scaffold can obtain a maximum compression strength of 12.8 MPa, a hardness of 437 HV, a maximum porosity of 60%, and a shrinkage rate of less than 10%. The half-peak width of each phase can be obtained by XRD spectrum statistics, and it is known that HA and TCP have a low crystallinity. The results of the scaffold immersed in SBF simulation body fluid show that less apatite is attached to the surface of the scaffold. The MRSA experimental results show that the antibacterial property of the scaffold is 62 CFU, which indicates that the scaffold maintains the antibacterial performance, but has a lower biological activity.

[0082] The specific embodiments of the present application are described above. It needs to be understood that the present application is not limited to the specific embodiments described above, and various modifications or changes can be made by those skilled in the art within the scope of the claims, which do not affect the essence of the present application.

Claims

1. A method for preparing a bioceramic bone scaffold with a gradient structure, characterized in that, The method includes the following steps: S1. Design a biological gradient structure model with different porosities and perform three-dimensional modeling; the biological gradient structure includes a structural gradient, with an outer layer of compact bone and an inner layer of cancellous bone; S2. Prepare filament material by mixing and pulping raw materials; the raw materials include nano-zirconia, tricalcium phosphate, hydroxyapatite and silver oxide powder. S3. Add the prepared filaments into the printer, and print the gradient structure layer by layer according to the preset printing strategy and printing scheme, and obtain the gradient bioceramic scaffold blank. S4. The gradient bioceramic scaffold blank is heat-treated and then cooled to room temperature in the furnace to obtain the bioceramic bone scaffold. In step S2, the outer layer filament material of the bone scaffold includes powder combination 1: Nano-ZrO2: 72~85%, HA: 12~18%, TCP: 2~6%, Ag2O: 1~4%; the inner layer filament material includes powder combination 2: Nano-ZrO2: 72~85%, HA: 2~6%, TCP: 12~18%, Ag2O: 1~4%.

2. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 1, characterized in that, In step S1, a biological structural model is established, and its geometry is simplified and processed. A gradient structure with a scaffold gap of 1.5~0.25mm is designed on its cross-section.

3. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 2, characterized in that, The gradient change is an isogradient change.

4. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 1, characterized in that, Both the outer and inner filament raw materials also include a binder with a mass ratio of 55-47%; the binder includes: PLA 50-70%, SA 8-10%, PW 20-40%.

5. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 1, characterized in that, In step S3, the printing process is set with a fill density of 85-93%, a wall thickness of 0.8-1.2 mm, a layer height of 0.8-1.2 mm, and a printing speed of 50-65 mm / min.

6. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 1, characterized in that, In step S4, before the heat treatment, the printed bracket blank is placed in a drying oven at a temperature of 50-65°C and a humidity of less than 8-12% and left to stand for 20-28 hours.

7. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 1 or 6, characterized in that, The heat treatment has a heating rate of 1~3℃ / min, a treatment temperature of 1150~1550℃, and a holding time of 1.5~2.5 hours.

8. A bioceramic bone scaffold with a gradient structure prepared by the method according to any one of claims 1-7.

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