Method for preparing biological ceramic bone scaffold with gradient structure by using 3DFP (three-dimensional Fabry-Perot) additive manufacturing

Abstract

The invention discloses a method for preparing a biological ceramic bone scaffold with a gradient structure by using 3DFP (three-dimensional Fabry-Perot) additive manufacturing. Comprising the steps of designing a biological gradient structure model; preparing a wire raw material containing nano zirconium oxide, tricalcium phosphate, hydroxyapatite and silver oxide powder, mixing and pulping to prepare a wire; adding the prepared wire into a printer, and completing layer-by-layer printing of a gradient structure according to a slicing path to obtain a stent blank; and carrying out heat treatment, and then carrying out furnace cooling to room temperature to obtain the biological ceramic bone scaffold. By deeply optimizing the composition ratio of the wire raw materials, the mechanical strength of the stent material is improved; meanwhile, through dual design of component gradient and structural gradient, cancellous bones with different components and structures are designed on the inner layer on the basis of ensuring high strength, hardness and bending resistance of compact bones, so that effective interaction between the scaffold and tissues or cells is ensured, adhesion, proliferation and differentiation of bone cells are promoted, and tissue repair and regeneration are facilitated.

Description

Technical Field

[0001] The invention relates to the fields of additive manufacturing and bionic structure design, and in particular to a method for preparing a bioceramic bone scaffold with a gradient structure by using 3DFP additive manufacturing. Background Art

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

[0003] (1) Poor mechanical strength: The existing technology uses collagen, alginate, gelatin or high molecular polymers to manufacture biological scaffold materials, but the compression strength, bending strength, stiffness and adjustability are poor. Since biological scaffolds need to withstand various mechanical loads in the human body, such as force, extrusion, shear, etc., for example, bone scaffolds will withstand muscle tension and pressure from surrounding tissues, etc., the aforementioned scaffold materials cannot meet the use requirements.

[0004] (2) Insufficient biodegradability and activity: Natural materials such as gelatin, alginate, gelatin or high molecular polymers may have adverse reactions; and their biodegradability and activity are insufficient.

[0005] (3) Complex scaffold structures are difficult to mold and have a long development cycle: Traditional sintering, gel injection molding, slip injection molding, and direct solidification injection molding scaffold structures require multiple steps such as mold design, manufacturing, and assembly. The preparation process is relatively slow and requires a long preparation time. The material utilization rate is low, and it is not easy to customize and it is difficult to achieve multifunctional complex structure manufacturing. Even using the existing mainstream bioscaffold additive manufacturing technologies such as slurry extrusion molding and fused deposition modeling, there are still some shortcomings. Extrusion molding additive manufacturing is difficult to achieve large-size pore manufacturing of scaffold materials, especially difficult to mold scaffolds with a spacing greater than 1mm. Fused deposition molding is limited by the choice of filament types, and it tends to manufacture thermoplastic materials such as wax, ABS, nylon, etc.

[0006] Bioceramic materials are widely used in the field of bone defect repair due to their excellent biocompatibility, bioactivity and mechanical properties. Therefore, researching and developing a bioceramic bone scaffold with excellent mechanical properties and bioactivity has important practical significance and application value.

[0007] Through searching the existing patent documents, it is found that CN200310122687.8 discloses a nano-zirconia toughened high-porosity calcium phosphate artificial bone scaffold and its preparation method; it is made by mixing nano-zirconia and hydroxyapatite in an appropriate proportion to form a slurry, and then applying it to a polyurethane sponge with an appropriate pore size and porosity and sintering. Due to the high porosity and appropriate pore size, not only is β-calcium phosphate easy to be degraded and absorbed, but also bone tissue is easy to grow into, the fusion speed is fast, and it is firmly combined with the host bone without producing 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 pore structure of natural bone. The present invention can realize the flexible regulation of the gradient distribution on the scaffold structure, so as to realize the hierarchical structure 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 properties, making it closer to natural bone tissue.

[0008] CN201510194743.1 discloses an additive manufacturing method for a multi-scale bionic artificial bone scaffold, wherein a biopolymer material and a bioceramic material are mixed with deionized water or an organic solvent to form a uniform slurry, and then freeze-dried to obtain a homogeneous powder, which is then mixed and stirred with deionized water or an organic solvent, and then vacuum-exhausted and quantitatively extruded by a screw pump. An XYZ motion device is used, and the pore shape, size and porosity inside the geometric model are designed by a computer program according to the three-dimensional geometric model of the bone defect obtained from the CT scan, and the motion trajectory of the extruded material is completed to complete the additive manufacturing. By using a degradable biocomposite material, the bone defect site is eventually replaced by the body's own tissue to meet the lifelong growth requirements of the human body. The method directly uses a screw pump to quantitatively extrude the required biomaterial, the dosage is accurate and controllable, and the clinical application cost of artificial bones is significantly reduced; it has the advantages of accurate dosage of printing materials, wide range of material applications, accurate and adjustable pore structure, and free molding of macroscopic geometric shapes. However, the technology described in the patent fails to achieve effective post-processing of printed scaffolds, resulting in mechanical and other properties that are difficult to meet requirements; during the activities of the organism, bones and joints are affected by various forces and pressures, which will be transmitted to the biological scaffold. If the strength and toughness of the scaffold are insufficient, deformation, fracture and other problems may occur. The present invention not only realizes the reasonable post-processing of gradient structure scaffolds and improves the physical bearing capacity of the structure, but also realizes the flexible balance and regulation of biological activity, mechanical properties and antibacterial properties through chemical composition transition design, which is of great significance for the scaffold to promote the maintenance of normal physiological functions and tissue repair of organisms. Summary of the invention

[0009] The present invention aims to solve the problems existing in the above-mentioned prior art and provides a method for preparing a bioceramic bone scaffold with a gradient structure using 3DFP additive manufacturing (3DFP (3D Filament Printing) is different from fused deposition manufacturing, i.e., FDM (Fused Deposition Modeling)). The 3DFP printing technology designed by the present invention can manufacture a scaffold in a relatively short time, is more flexible and efficient, and can design and manufacture scaffolds with complex shapes and high personalization as needed. In terms of mechanical strength, the prepared Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold has high compressive strength and bending strength, can withstand certain compression and bending loads, and has moderate stiffness, which can provide sufficient support without being too stiff to affect bone healing. Most importantly, the mechanical properties of the Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold can be flexibly optimized by adjusting its porosity, particle size and other parameters to meet different biomechanical requirements. After the addition of Ag2O, which has a lower decomposition temperature, silver atoms are formed due to the strong negative charge of silver ions, and oxygen ions form oxygen and escape, so more oxygen vacancies are left in the scaffold. The presence of a large number of oxygen vacancies is conducive to the formation of a denser structure of the material, thereby synergistically improving the mechanical properties of the scaffold, while also having excellent antibacterial properties. In terms of biodegradability and activity, the Nano-ZrO2-HA-TCP-Ag2O ceramic scaffold prepared by the present invention is a biodegradable artificial bone scaffold that can be decomposed and gradually absorbed by enzymes in the human body and eventually 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, help accelerate bone healing, and has good antibacterial properties.

[0010] Specifically, the purpose of the present invention is achieved through the following technical solutions:

[0011] The present invention provides a method for preparing a bioceramic bone scaffold with a gradient structure, the method comprising the following steps:

[0012] S1. Design a bio-gradient structure model with different porosities and perform three-dimensional modeling;

[0013] S2, preparing wire raw materials, mixing and slurrying, and preparing wire; the wire raw materials include nano zirconium oxide, tricalcium phosphate, hydroxyapatite and silver oxide powder;

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

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

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

[0017] As an implementation scheme of the present invention, in step S1, a biological structure model is established, geometrically simplified and processed, and a gradient structure with a stent gap gradiently changing from 1.5 to 0.25 mm is designed on its cross section.

[0018] As an embodiment of the present invention, the gradient change is an isogradient change.

[0019] In some embodiments, the pore structure of the stent is designed according to an isogradient change, and includes a total of 5 pore transition regions, that is, the pores on one side are 1.5 mm, and gradually change to 1.25 mm, 1 mm, 0.75 mm, 0.5 mm, and 0.25 mm from one side to the other.

[0020] As an embodiment of the present invention, in step S1, the biogradient structure includes a composition gradient, and the material composition of the outer layer and the inner layer of the bone scaffold is different.

[0021] As an implementation scheme of the present invention, in step S2, a 3DFP additive manufacturing method is adopted.

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

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

[0024] As an embodiment of the present invention, both the outer layer wire material and the inner layer wire material further include a binder accounting for 55 to 47% by weight.

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

[0026] As an embodiment of the present invention, in step S3, the printing process sets the filling density to 85-93%, the wall thickness to 0.8-1.2 mm, the layer height to 0.8-1.2 mm, and the printing speed to 50-65 mm / min. In some implementation examples, the printing process sets the filling density to 90%, the wall thickness to 1.0 mm, the layer height to 1 mm, and the printing speed to 60 mm / min.

[0027] As an embodiment of the present invention, the heat treatment further includes placing the printed bracket blank in a drying oven at a temperature of 50-65°C and a humidity of less than 8-12% for 20-28 hours. In some implementation examples, the printed bracket blank is placed in a drying oven at a temperature of 60°C and a humidity of less than 10% for 24 hours.

[0028] As an embodiment of the present invention, the heating rate of the heat treatment is 1-3°C / min, the treatment temperature is 1150-1550°C, and the holding time is 1.5-2.5 hours.

[0029] The bioceramic bone scaffold with gradient structure prepared by the aforementioned method also falls within the protection scope of the present invention.

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

[0031] (1) Optimizing mechanical strength: To address the problem of poor mechanical strength of biological scaffold materials, the ratio of nano-zirconia, hydroxyapatite, tricalcium phosphate, and silver oxide is optimized in depth to improve the mechanical strength of the scaffold materials. At the same time, the dual design concepts of composition gradient and structure gradient are used to imitate solid bone: on the basis of ensuring the high strength, hardness, and bending resistance of compact bone, the inner layer is designed with cancellous bone of different composition and structure, thereby ensuring that the scaffold interacts effectively with tissues or cells, promoting the adhesion, proliferation, and differentiation of bone cells, and facilitating tissue repair and regeneration.

[0032] (2) Improving biodegradability and activity: To address the problem of insufficient biodegradability and activity of scaffold materials, the present invention precisely regulates the biodegradability and activity by adjusting the content and surface properties of nano-zirconia, etc. On the one hand, the surface reactivity of the scaffold material is improved to make it easier to be decomposed by hydrolases in the body, and chemical modification makes the nanoparticles with positive charges on the surface easier to be adsorbed onto the cell surface, thereby promoting cell attachment and proliferation 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, thereby greatly improving the biological activity of the scaffold.

[0033] (3) Shorten the development cycle: 3DFP printing technology can effectively solve the problems of difficult molding of complex scaffold structures and long development cycles, and improve the preparation efficiency and quality of complex biological scaffold structures. When using 3DFP printing, the printing speed, extrusion speed, layer height and other printing parameters are optimized, and the slurry formula, printing strategy, post-processing scheme and other aspects are adjusted and designed to meet different clinical needs and application scenarios, greatly shortening the development cycle while having good customizability and plasticity. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0035] Figure 1 The process flow chart of preparing bioceramic bone scaffolds with gradient structures using 3DFP additive manufacturing;

[0036] Figure 2 Schematic diagram of the preparation process of bioceramic bone scaffolds with gradient structures using 3DFP additive manufacturing;

[0037] Figure 3 Top view and side view of the local structure of the bioceramic bone scaffold with gradient structure manufactured using 3DFP additive manufacturing. DETAILED DESCRIPTION

[0038] The present invention is described in detail below in conjunction with examples. The following examples will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, some adjustments and improvements can also be made without departing from the inventive concept. These all belong to the protection scope of the present invention. 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 bioceramic bone scaffold with a double-layer gradient structure, including the design of the gradient structure, the composition configuration of the slurry, the formulation of the printing strategy, the setting of the printing parameters, and the post-processing scheme, such as Figure 1 As shown:

[0041] Design of gradient structure: Design a biological gradient structure model with different porosities and perform three-dimensional modeling. The gradient structure of a biological scaffold refers to the realization of a certain chemical and geometric gradient distribution in the scaffold structure to simulate the tissue structure and function in the organism. The use of three-dimensional modeling software can help designers design and optimize the gradient structure of biological scaffolds more accurately and efficiently. With the help of CT or MRI scan images, a biological structure model is established, and it is geometrically simplified and processed. A gradient structure with different porosities (the scaffold gap is a gradient change of 1.5 to 0.25 mm) is designed on its cross section. Specifically, the pore structure design of the scaffold in this embodiment follows an equal gradient change, and includes a total of 5 pore transition regions, that is, the pores on one side are 1.5 mm, and gradually change from one side to the other side to 1.25 mm, 1 mm, 0.75 mm, 0.5 mm, and 0.25 mm. The pore composition design of the scaffold is divided into inner and outer layers, and includes a total of 1 component transition region, that is, one side is formula 1 and the other side is formula 2. Specifically, Figure 2 As shown, firstly, the gradient biological scaffold is designed, and the .stl file is generated for slicing, and then the prepared wire raw material containing different component ratios is extruded from the nozzle through the extrusion and heating mechanism to realize the additive manufacturing of the gradient scaffold on the building platform.

[0042] Wire composition configuration: Prepare wire raw materials with different proportions, including nano zirconium oxide, tricalcium phosphate, hydroxyapatite, and silver oxide powder. The steps of slurry configuration specifically include the following aspects: prepare materials, weigh materials, mix and stir.

[0043] (1) Prepare and weigh materials: Use nano zirconium oxide powder, tricalcium phosphate powder, hydroxyapatite powder, and silver oxide powder as the scaffold matrix, and weigh various powders according to the formula ratio. The present invention involves two formula ratios: 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%, and put the weighed powder into a dry container. Use a stirrer to mix the powders of the specified formula evenly for 2 hours to ensure that all ingredients are fully mixed. The powder is added to a mixture of PLA (polylactic acid), SA (stearic acid), and PW (paraffin) (PLA: 50-70%, SA: 8-10%, PW: 20-40%) and made into a filament by an extruder for use; wherein the loading mass ratio of the powder to the mixture is powder: 45-53%, mixture: 55-47%. In this embodiment, the powder formula ① 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 the powder to the mixture is: powder: 48%, mixture: 52%.

[0044] Formulation of printing strategy: Develop printing strategy and printing scheme, and complete the layer-by-layer printing of gradient structure according to the slicing path. Set the filling density to 90% during the printing process to ensure the tight structure of the scaffold and provide sufficient strength and stability. Set the wall thickness to 1.0mm to increase the overall strength and durability of the scaffold and ensure the tightness of the external structure. Set the layer height to 1mm and the printing speed to 60mm / min to obtain high resolution and surface quality. Add the prepared filament to the printer and manufacture the bioceramic scaffold according to the above printing strategy and scheme. Figure 2 The specific process is as follows: add the wire raw material into the 3DFP printer including the Z-axis column, the building platform and the heating wire device. The wire is heated and melted and extruded through the printing nozzle. As the Z-axis support mechanical device completes the layer-by-layer manufacturing of the blank on the building platform, when the printing reaches the composition and structure gradient design position, the structure and composition gradient on the blank can be flexibly controlled 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 treatment temperature is 1150-1550°C, the insulation time is 1.5-2.5 hours, and then it is cooled to room temperature with the furnace. In this embodiment, the printed blank scaffold is placed in a drying furnace 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, and the heating rate is controlled at 1.5°C / min. When the temperature rises to 1350°C and is kept for 2.5 hours, the binder is burned off and the strength of the scaffold is increased, and then it is cooled with the furnace.

[0046] The bioceramic scaffold prepared by the process has the characteristics of compactness and high strength on the outside, looseness and strong biological activity on the inside, and gradient arrangement, such as Figure 3 As shown, the scaffold has a designed structural gradient structure in the horizontal direction indicated by the arrow, the dense pore position is the component of formula 1, the loose pore position is the component of formula 2, and the connectivity between the scaffolds is good. According to GB / T1964-1996, GB / T 16534-2009 and GB / T 1966-1996, the performance test results show that the scaffold can obtain a maximum compression strength of 16.2MPa, the hardness remains 513HV, the maximum porosity can be achieved 65%, and the shrinkage rate is less than 10%. At the same time, the half-peak width of each phase is statistically analyzed by XRD spectrum, and HA and TCP have a lower crystallinity. At the same time, the analysis results of the scaffold immersed in SBF simulated body fluid show that more apatite is attached to the surface of the scaffold. The antibacterial property of the scaffold is 75CFU through the MRSA test results, which shows that the scaffold maintains good biological activity and antibacterial properties. The gradient bioceramic scaffold prepared by this preparation method not only ensures the effective transportation of nutrients and cell growth inside the artificial bone scaffold, but also improves the overall bearing capacity and antibacterial properties. Unlike traditional mold forming methods, this preparation method can be customized according to individual patient differences, greatly shortening the production cycle of bioceramic scaffolds.

[0047] Example 2

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

[0049] Wire composition configuration: Prepare wire raw materials with different proportions, including nano zirconium oxide, tricalcium phosphate, hydroxyapatite, and silver oxide powder. The steps of slurry configuration specifically include the following aspects: prepare materials, weigh materials, mix and stir.

[0050] (1) Prepare and weigh materials: Use nano zirconium oxide powder, tricalcium phosphate powder, hydroxyapatite powder, and silver oxide powder as the scaffold matrix, and weigh various powders according to the formula ratio. Formula ① is Nano-ZrO2: 83%, HA: 13%, TCP: 3%, Ag2O: 1%, ② Nano-ZrO2: 75%, HA: 6%, TCP: 18%, Ag2O: 1%. The mixture ratio is: PLA: 50%, SA: 10%, PW: 40%. The mass ratio of powder to mixture is: powder: 52%, mixture: 48%.

[0051] Formulation of printing strategy: same as in Example 1.

[0052] Post-processing scheme: After the gradient bioceramic scaffold blank is manufactured, the printed blank scaffold is placed in a drying furnace at 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 with a heating rate of 2.5°C / min. When the temperature rises to 1500°C and is kept for 2 hours, the binder is burned off and the strength of the scaffold is increased, and then it is 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 compression strength of 22.3MPa, the hardness remains at 601HV, the maximum porosity can reach 76%, and the shrinkage rate is less than 10%. At the same time, the half-peak width of each phase is statistically analyzed by XRD spectrum, and HA and TCP produce lower crystallinity. At the same time, the analysis results of the scaffold immersed in SBF simulated body fluid show that more apatite is attached to the surface of the scaffold. The antibacterial property of the scaffold is 120CFU through the MRSA test results, which shows that the scaffold maintains good biological activity and antibacterial properties. The gradient bioceramic scaffold prepared by this preparation method not only ensures the effective transport of nutrients and cell growth inside the artificial bone scaffold, but also improves the overall bearing capacity. Unlike the traditional mold forming method, this preparation method can be customized according to individual differences of patients, greatly shortening the production cycle of bioceramic scaffolds.

[0054] Example 3

[0055] The design of the gradient structure is the same as that in Example 1.

[0056] Wire composition configuration: Prepare wire raw materials with different proportions, including nano zirconium oxide, tricalcium phosphate, hydroxyapatite, and silver oxide powder. The steps of slurry configuration specifically include the following aspects: prepare materials, weigh materials, mix and stir.

[0057] (1) Prepare and weigh materials: Use nano zirconium oxide powder, tricalcium phosphate powder, hydroxyapatite powder, and silver oxide powder as the scaffold matrix, and weigh various powders according to the formula ratio. Formula ① has a ratio of 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 to mixture is: powder: 50%, mixture: 50%.

[0058] Formulation of printing strategy: same as in Example 1.

[0059] Post-processing scheme: After the gradient bioceramic scaffold blank is manufactured, the printed blank scaffold is placed in a drying furnace at 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°C / min. When the temperature rises to 1150°C and is kept for 2 hours, the binder is burned off and the strength of the scaffold is increased, and then it is cooled with the furnace.

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

[0061] Comparative Example 1

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

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

[0064] Performance tests were carried out according to GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996 standards. The results showed that the bioceramic scaffold can obtain a maximum compressive strength of 7.2MPa, a hardness of 308HV, a maximum porosity of 79%, and a shrinkage rate of less than 10%. At the same time, the half-peak width of each phase was statistically analyzed through the XRD spectrum, and it was found that HA and TCP produced lower crystallinity. At the same time, the analysis results of the scaffold immersed in SBF simulated body fluid showed that more apatite was attached to the surface of the scaffold. The MRSA experimental results showed that the antibacterial property of the scaffold was 215CFU, which showed that the scaffold maintained good biological activity, but the antibacterial performance was poor.

[0065] Comparative Example 2

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

[0067] In the composition 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 ratio. Formula ① ratio is HA: 100%; ② Nano-ZrO2: 50%, HA: 50%. The mixture ratio is: PLA: 72%, SA: 8%, PW: 20%. The mass ratio of powder and mixture is: powder: 50%, mixture: 50%.

[0068] Performance tests were carried out according to GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996 standards. The results showed that the bioceramic scaffold can obtain a maximum compressive strength of 1.02MPa, a hardness of 172HV, a maximum porosity of 78%, and a shrinkage rate of less than 10%. At the same time, the half-peak width of each phase was statistically analyzed through the XRD spectrum, and it was found that HA and TCP produced lower crystallinity. At the same time, the analysis results of the scaffold immersed in SBF simulated body fluid showed that more apatite was attached to the surface of the scaffold. The MRSA experimental results showed that the antibacterial property of the scaffold was 223CFU, which showed that the scaffold maintained very good biological activity, but the antibacterial and mechanical properties were poor.

[0069] Comparative Example 3

[0070] The design and post-processing scheme of the gradient structure in this comparative example are the same as those in Example 3; the difference is that:

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

[0072] Development of printing strategy: Develop printing strategies and printing plans, and complete layer-by-layer printing of gradient structures according to the slicing path. Set the filling density to 90% during the printing process to ensure that the structure of the scaffold is tight and provide sufficient strength and stability. Set the wall thickness to 1.0mm to increase the overall strength and durability of the scaffold and ensure the tightness of the external structure. Set the layer height to 1mm and the printing speed to 60mm / min to obtain high resolution and surface quality. Add the prepared filament to the printer, and manufacture the bioceramic scaffold according to the above printing strategy and plan. When the printing reaches the structural gradient design position, the filament above the extruder is switched to achieve flexible regulation of the structure and composition gradient on the blank.

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

[0074] Comparative Example 4

[0075] The design of the gradient structure, the formulation of the printing strategy, and the post-processing scheme in this comparative example are the same as those in Example 3; the difference is that:

[0076] In the composition configuration of the wire, the ratio of formula ① is Nano-ZrO2: 60%, HA: 30%, 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%.

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

[0078] Comparative Example 5

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

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

[0081] Performance tests were carried out according to GB / T 1964-1996, GB / T 16534-2009 and GB / T 1966-1996 standards. The results showed that the bioceramic scaffold can obtain a maximum compressive strength of 12.8 MPa, a hardness of 437 HV, a maximum porosity of 60%, and a shrinkage rate of less than 10%. At the same time, the half-peak width of each phase was statistically analyzed through the XRD spectrum, and it was found that HA and TCP produced lower crystallinity. At the same time, the analysis results of the scaffold immersed in SBF simulated body fluid showed that less apatite was attached to the surface of the scaffold. The MRSA experimental results showed that the antibacterial property of the scaffold was 62 CFU, which showed that the scaffold maintained antibacterial properties but had low biological activity.

[0082] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A method for preparing a bioceramic bone scaffold with a gradient structure, characterized in that: The method comprises the following steps: S1. Design a bio-gradient structure model with different porosities and perform three-dimensional modeling; S2, preparing wire raw materials, mixing and slurrying, and preparing wire; the wire raw materials include nano zirconium oxide, tricalcium phosphate, hydroxyapatite and silver oxide powder; S3, adding the prepared filament into the printer, and completing the layer-by-layer printing of the gradient structure according to the preset printing strategy and printing scheme and the slicing path to obtain a gradient bioceramic scaffold blank; S4, heat treating the gradient bioceramic scaffold blank, and then cooling it to room temperature in a furnace to obtain the bioceramic bone scaffold.

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 structure model is established, geometrically simplified and processed, and a gradient structure with a stent gap varying in a gradient of 1.5 to 0.25 mm 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: In step S1, the biogradient structure includes a composition gradient, and the material composition of the outer layer and the inner layer of the bone scaffold is different.

5. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 4, characterized in that: In step S2, the outer layer wire 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 wire material includes powder combination 2: Nano-ZrO2: 72-85%, HA: 2-6%, TCP: 12-18%, Ag2O: 1-4%.

6. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 5, characterized in that: The outer layer wire material and the inner layer wire material both further include a binder with a mass percentage of 55-47%; the binder includes: PLA 50-70%, SA 8-10%, and PW 20-40%.

7. 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 sets the filling density to 85-93%, the wall thickness to 0.8-1.2 mm, the layer height to 0.8-1.2 mm, and the printing speed to 50-65 mm / min.

8. 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 with a temperature of 50-65° C. and a humidity of less than 8-12% for 20-28 hours.

9. The method for preparing a bioceramic bone scaffold with a gradient structure according to claim 1 or 8, characterized in that: The heating rate of the heat treatment is 1-3°C / min, the treatment temperature is 1150-1550°C, and the heat preservation time is 1.5-2.5 hours.

10. A bioceramic bone scaffold with a gradient structure prepared according to the method according to any one of claims 1 to 9.

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