3D-printed ceramic slurry, 3D-printed ceramic support and preparation method and application thereof

Abstract

The application belongs to the technical field of biomedical materials, and particularly relates to a 3D printing ceramic slurry, a 3D printing ceramic support and a preparation method and application thereof. The 3D printing ceramic slurry provided by the application comprises ceramic powder, photosensitive resin, photoinitiator, dispersant and yellow colorant, the dispersant is oleic acid, linoleic acid and oleic acid amine, and the yellow colorant is curcumin, acid yellow 23 and beta-carotene. The application can improve the light scattering phenomenon of the ceramic powder on the photosensitive resin, thereby effectively improving the quality of the 3D printing ceramic support. The preparation method of the 3D printing ceramic support solves the technical problem that residual slurry of the 3D printing ceramic support is difficult to remove, improves the problem that the porosity and pore connectivity are reduced due to the plugging of holes caused by insufficient removal of residual slurry, and can collect the residual slurry to realize secondary utilization of the slurry and avoid resource waste.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a 3D printing ceramic slurry, a 3D printing ceramic scaffold, its preparation method, and its application. Background Technology

[0002] 3D printed bioceramic materials are an innovative combination of bioceramics and additive manufacturing technology. The main materials include hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), etc., which have good biocompatibility. These materials with specific biological or physiological functions have the following characteristics: (1) osteoconductivity: their chemical composition (such as hydroxyapatite and tricalcium phosphate) is similar to the inorganic components of bone tissue, which can provide attachment sites for bone cells and guide new bone to grow along the surface or internal pores of the material, so as to achieve direct binding with the host bone; (2) bioactivity: some bioceramics (such as bioactive glass) can form a bone-like apatite layer in vivo through surface chemical reaction, which further promotes bone integration and accelerates the repair process; (3) degradation regulation: degradable bioceramics (such as β-tricalcium phosphate) can be gradually degraded during bone regeneration, releasing nutrients such as calcium ions, and are eventually replaced by new bone, avoiding removal by secondary surgery. 3D printed bioceramic materials can be customized into complex structures on demand through layer-by-layer printing, precisely matching the shape of bone defects in patients. At the same time, they can controllably construct interconnected pores of specific sizes, providing key spaces for cell infiltration and blood vessel regeneration. They are mainly used in orthopedic implants such as artificial bone scaffolds and spinal fusion devices, solving the pain point of traditional ceramic processing being unable to prepare complex shapes.

[0003] Photopolymer 3D printing technology, with its strong ability to form complex structures, has become an important method for fabricating bioceramic scaffolds. In the field of photopolymer 3D printing ceramic materials, the ceramic slurry directly affects the dimensional accuracy and structure of the 3D printed product. Because the ceramic powder in the slurry scatters ultraviolet light, the curing width increases, leading to decreased accuracy and significant deviations in porosity from design values. Furthermore, for photopolymer 3D printed ceramic scaffolds with complex, irregular structures, existing methods for removing photosensitive resin are insufficient to remove residual slurry from the interconnected pores. The residual ceramic powder in the slurry remains in the pore structure, severely affecting the porosity and pore connectivity of the 3D printed ceramic scaffold. In addition, existing processes almost entirely fail to allow for the reuse of residual slurry, resulting in slurry waste. Summary of the Invention

[0004] This invention addresses the technical challenges of existing technologies, such as the scattering of ultraviolet light by ceramic powder leading to increased curing width, resulting in decreased precision and significant deviations in porosity from design values. It provides a 3D printing ceramic slurry and its preparation method, which not only effectively improves printing precision but also mitigates the problem of porosity deviation from design values. Furthermore, this invention provides a 3D printing ceramic scaffold and its preparation method, solving the problem of difficult removal of residual slurry from photopolymerized 3D printing ceramic scaffolds. It also enables the collection and reuse of the residual slurry, avoiding resource waste.

[0005] The technical solution of this invention is: A 3D printing ceramic slurry includes ceramic powder, photosensitive resin, photoinitiator, dispersant and yellow colorant.

[0006] Furthermore, the ceramic powder is any one or more of hydroxyapatite, biphasic calcium phosphate, calcium carbonate, calcium silicate, and calcium phosphate.

[0007] Furthermore, the calcium phosphate includes any one or more of tricalcium phosphate, β-tricalcium phosphate, and α-tricalcium phosphate.

[0008] Furthermore, the dispersant is oleic acid, linoleic acid, or oleic acid amine; the yellow colorant is curcumin, acid yellow 23, or β-carotene.

[0009] Furthermore, in the 3D printing ceramic slurry, the photosensitive resin is composed of 1,6-hexanediol diacrylate, hydroxyethyl acrylate, and trimethylolpropane trimethacrylate.

[0010] Furthermore, the volume ratio of 1,6-hexanediol diacrylate, hydroxyethyl acrylate, and trimethylolpropane trimethacrylate in the photosensitive resin is (4-8):(2-4):1.

[0011] Furthermore, the photoinitiator is diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide.

[0012] Furthermore, the mass ratio of the ceramic powder, dispersant, and yellow colorant is 1000:(0.8-1.2)(0.05-1).

[0013] Furthermore, the mass-to-volume ratio of the ceramic powder, photoinitiator, and photosensitive resin is (2.4-3.7) g : (0.009-0.1) g : 1 mL.

[0014] A method for preparing a 3D printing ceramic slurry includes the following steps: (1) Mix the dispersant and anhydrous ethanol, stir well, and prepare solution A; (2) Mix the ceramic powder, yellow colorant and solution A obtained in step (1), add anhydrous ethanol, and ball mill the mixture for the first time. Then dry the mixture to obtain yellow powder. (3) Mix the photosensitive resin with the yellow powder obtained in step (2), perform a second ball milling, add the photoinitiator, and perform a third ball milling to obtain a mixture of materials and balls; (4) Centrifuge the mixture of pellets obtained in step (3) to obtain 3D printing ceramic slurry.

[0015] Further, in step (1), the mass-to-volume ratio of the dispersant and anhydrous ethanol is (2-5) g: 1000 mL.

[0016] Furthermore, in step (2), the mass-to-volume ratio of the ceramic powder, anhydrous ethanol, and solution A is (2-4) g: 1 mL: 1 mL.

[0017] Furthermore, in step (2), the first ball milling process is as follows: ball milling at a speed of 300-600 rpm for 2-6 hours.

[0018] Further, in step (3), the process of the second ball milling is: ball milling at a speed of 300-600 rpm for 2-6 hours; the process of the third ball milling is: ball milling at a speed of 300-600 rpm for 0.4-1 hours.

[0019] Furthermore, in step (4), the centrifugation process is as follows: centrifuge at a rate of 300-800 rpm for 2-10 min.

[0020] A method for fabricating a 3D-printed ceramic scaffold includes the following steps: S1 The above-mentioned 3D printing ceramic slurry or the 3D printing ceramic slurry prepared by the above-mentioned preparation method is printed by photopolymerization 3D printing process to obtain a blank composed of uncured ceramic slurry and cured 3D printing ceramic support. S2 Centrifuge the blank obtained in step S1 and collect the separated uncured ceramic slurry and cured 3D printed ceramic support; S3 involves immersing the cured 3D-printed ceramic scaffold in a cleaning solution for ultrasonic cleaning; rinsing with running water; ultrasonically cleaning with purified water; and drying to obtain an intermediate 3D-printed ceramic scaffold product. S4 involves sintering, cleaning, and drying the intermediate 3D printed ceramic support obtained in step S3 to obtain the final product.

[0021] Furthermore, in step S1, the process parameters for printing using photopolymerization 3D printing are: layer thickness: 25-100 μm, exposure power: 5-20 mW / cm². 2Exposure time: 3-20s.

[0022] Furthermore, in step S2, the centrifugation process parameters are: centrifugation speed of 500-4000 rpm and centrifugation time of 1-10 min.

[0023] Furthermore, in step S3, the ratio of the cured 3D printed ceramic support to the cleaning solution is 1g:(2-20)mL.

[0024] Further, in step S3, the ultrasonic cleaning time is 5-15 minutes and the number of times is 1-2; the rinsing time with running water is 1-3 minutes; and the ultrasonic cleaning time with purified water is 5-10 minutes and the number of times is 1-3.

[0025] Furthermore, the cleaning solution consists of a cleaning agent and purified water, wherein the cleaning agent consists of sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether.

[0026] Furthermore, the mass-to-volume ratio of the cleaning agent to purified water in the cleaning solution is 45-60 g / L; the mass ratio of sodium dodecylbenzenesulfonate to fatty alcohol polyoxyethylene ether in the cleaning agent is (15-20):1.

[0027] Furthermore, in step S3, the drying process parameters are: temperature: 50-100℃, time: 2-6h.

[0028] Further, in step S4, the sintering process parameters are as follows: raising the temperature to 250-350℃ at a heating rate of 0.2-1℃ / min and holding for 1-3 hours; raising the temperature to 550-700℃ at a heating rate of 0.2-1℃ / min and holding for 2-4 hours; raising the temperature to 1000-1200℃ at a heating rate of 2-5℃ / min and holding for 4-6 hours.

[0029] Furthermore, in step S4, the cleaning method is ultrasonic cleaning.

[0030] Furthermore, in step S4, the drying process parameters are: temperature: 60-100℃, time: 2-6h.

[0031] A 3D printed ceramic scaffold prepared according to the above preparation method.

[0032] An application of a 3D-printed ceramic scaffold prepared according to the above preparation method in bone fillers, bone scaffolds, or as a scaffold for in vitro cell culture.

[0033] Compared with the prior art, the present invention has the following advantages: (1) The 3D printing ceramic slurry of the present invention improves the dispersion stability of ceramic powder in photosensitive resin by adding a dispersant; by adding a yellow colorant, the degree of ultraviolet light scattering of ceramic powder is reduced, effectively improving the dimensional accuracy of 3D printed ceramic support, solving the technical problem of ultraviolet light scattering of ceramic powder causing an increase in curing width and thus a decrease in accuracy in the prior art, and solving the problem of porosity deviating from the design value.

[0034] (2) The 3D printed ceramic support obtained by using the 3D printing ceramic slurry described in this invention can improve the light scattering phenomenon of ceramic powder on photosensitive resin, thereby effectively improving the quality of 3D printed ceramic support.

[0035] (3) In the preparation method of the 3D printed ceramic support described in this invention, the "centrifugation followed by cleaning" process is used to remove impurities from the blank. The advantages are: a. Centrifuging the 3D printed blank first can effectively remove the uncured ceramic slurry from the blank. In the subsequent cleaning process, the slurry is easier to remove, the cleaning process shortens the number of cleaning times, and saves time; b. After centrifugation, the separated ceramic slurry can be collected to realize the secondary use of the printing slurry, which significantly improves the utilization rate of the printing slurry and saves costs. Attached Figure Description

[0036] Figure 1 The image shows the appearance of the blank prepared in Example 5; Figure 2 This is an appearance image of the intermediate 3D-printed ceramic scaffold prepared in Example 5; Figure 3 This is an appearance image of the intermediate 3D-printed ceramic scaffold prepared in Example 8; Figure 4 This is an appearance image of the intermediate 3D-printed ceramic scaffold prepared in Example 9; Figure 5 This is an image of the intermediate 3D-printed ceramic scaffold prepared in Comparative Example 7. Figure 6 This is an image of the intermediate 3D-printed ceramic scaffold prepared in Comparative Example 8. Figure 7 This is an image of the intermediate 3D-printed ceramic scaffold prepared in Comparative Example 9. Figure 8 CT image of the intermediate 3D-printed ceramic scaffold prepared in Example 10; Figure 9 CT image of the 3D-printed ceramic scaffold prepared in Example 10; Figure 10 X-ray image of the left femoral condyle 8 weeks after implantation of the cylindrical 3D-printed ceramic scaffold prepared in Example 11; Figure 11 X-ray image of the left femoral condyle 12 weeks after implantation of the cylindrical 3D-printed ceramic scaffold prepared in Example 11; Figure 12 X-ray image of the left femoral condyle 26 weeks post-implantation of the cylindrical 3D-printed ceramic scaffold prepared in Example 11; Figure 13 HE staining pathological image of animal hard tissue sections (0.3×) 8 weeks after implantation of the cylindrical 3D printed ceramic scaffold prepared in Example 11. Figure 14 HE staining pathological image of animal hard tissue sections 8 weeks after implantation of the cylindrical 3D printed ceramic scaffold prepared in Example 11 (5×). Figure 15 HE staining pathological image of animal hard tissue sections 12 weeks after implantation of the cylindrical 3D printed ceramic scaffold prepared in Example 11 (0.3×). Figure 16 HE staining pathological image of animal hard tissue sections 12 weeks after implantation of the cylindrical 3D printed ceramic scaffold prepared in Example 11 (5×). Figure 17 HE staining pathological image of animal hard tissue sections 26 weeks after implantation of the cylindrical 3D printed ceramic scaffold prepared in Example 11 (0.3×). Figure 18 HE staining pathological image of animal hard tissue sections 26 weeks after implantation of the cylindrical 3D printed ceramic scaffold prepared in Example 11 (5×). Detailed Implementation

[0037] The present invention will be further described below through specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not depart from the basic idea of ​​the present invention, they are all within the scope of the present invention.

[0038] Example 1: A 3D printing ceramic slurry and its preparation method A 3D printing ceramic slurry includes tricalcium phosphate powder, photosensitive resin, photoinitiator, dispersant, and Acid Yellow 23. The photosensitive resin is composed of 1,6-hexanediol diacrylate, hydroxyethyl acrylate, and trimethylolpropane trimethacrylate in a volume ratio of 6:3:1. The photoinitiator is diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide. The dispersant is oleic acid. The mass ratio of tricalcium phosphate powder, oleic acid, and Acid Yellow 23 is 1000:1:0.25. The mass-volume ratio of tricalcium phosphate powder, photoinitiator, and photosensitive resin is 3g:0.01g:1mL. The method for preparing 3D printing ceramic slurry includes the following steps: (1) Mix 0.12g of oleic acid and 40mL of anhydrous ethanol evenly to prepare solution A; (2) Mix 120g tricalcium phosphate powder, 0.03g acid yellow 23, solution A prepared in step (1) and 40mL anhydrous ethanol, and ball mill for the first time at 450rpm for 4h. Dry to obtain yellow powder. (3) Mix 1,6-hexanediol diacrylate, hydroxyethyl acrylate and trimethylolpropane trimethacrylate in a volume ratio of 6:3:1 to prepare 40 mL of photosensitive resin. Add the yellow powder obtained in step (2) and ball mill for a second time at 480 rpm for 4 h. Add 0.4 g of photoinitiator and ball mill for a third time at 450 rpm for 0.5 h to obtain a mixture of material and ball. (4) Pour the mixture of pellets obtained in step (3) into a centrifuge tank and centrifuge at 500 rpm for 3 min to obtain 3D printing ceramic slurry.

[0039] Example 2: A 3D printing ceramic slurry and its preparation method The only difference is that the mass ratio of "tricalcium phosphate powder, oleic acid, and acid yellow 23 in Example 1 is 1000:1:0.25" is replaced with "tricalcium phosphate powder, oleic acid, and acid yellow 23 in mass ratio is 1000:1:0.05". The rest of the process is the same as in Example 1, and the preparation steps are the same.

[0040] Example 3: A 3D printing ceramic slurry and its preparation method The only difference is that the mass ratio of "tricalcium phosphate powder, oleic acid, and acid yellow 23 is 1000:1:0.25" in Example 1 is replaced with "tricalcium phosphate powder, oleic acid, and acid yellow 23 is 1000:1:1". The rest of the process is the same as in Example 1, and the preparation steps are the same.

[0041] Example 4: A 3D printing ceramic slurry and its preparation method A 3D printing ceramic slurry includes hydroxyapatite powder, photosensitive resin, photoinitiator, oleic acid amine, and curcumin; the photosensitive resin is composed of 1,6-hexanediol diacrylate, hydroxyethyl acrylate, and trimethylolpropane trimethacrylate in a volume ratio of 4:2:1; the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide; the dispersant is oleic acid amine; the mass ratio of hydroxyapatite powder, oleic acid amine, and curcumin is 1000:1:0.25; the mass-volume ratio of hydroxyapatite powder, photoinitiator, and photosensitive resin is 2.4 g:0.012 g:1 mL.

[0042] The method for preparing 3D printing ceramic slurry includes the following steps: (1) Mix 0.12g of oleic acid and 40mL of anhydrous ethanol evenly to prepare solution A; (2) Mix 120g of hydroxyapatite powder, 0.03g of curcumin, solution A prepared in step (1) and 40mL of anhydrous ethanol, and ball mill for the first time at 500rpm for 5h. Then dry to obtain yellow powder. (3) Mix 1,6-hexanediol diacrylate, hydroxyethyl acrylate and trimethylolpropane trimethacrylate in a volume ratio of 4:2:1 to prepare 50 mL of photosensitive resin. Add the yellow powder obtained in step (2) and ball mill for a second time at 500 rpm for 5 h. Add 0.6 g of photoinitiator and ball mill at 400 rpm for 0.4 h to obtain a mixture of material and ball. (4) Pour the mixture of pellets obtained in step (3) into a centrifuge tank and centrifuge at 400 rpm for 5 min to obtain 3D printing ceramic slurry.

[0043] Comparative Example 1: A 3D Printing Ceramic Slurry and Its Preparation Method The only difference is that the mass ratio of "tricalcium phosphate powder, oleic acid, and acid yellow 23 is 1000:1:0.25" in Example 1 is replaced with "tricalcium phosphate powder, oleic acid, and acid yellow 23 is 1000:1:0". The rest of the process is the same as in Example 1, and the preparation steps are the same.

[0044] Comparative Example 2: A 3D Printing Ceramic Slurry and Its Preparation Method The only difference is that the mass ratio of "tricalcium phosphate powder, oleic acid, and acid yellow 23 in Example 1 is 1000:1:0.25" is replaced with "tricalcium phosphate powder, oleic acid, and acid yellow 23 in mass ratio is 1000:1:0.01". The rest of the process is the same as in Example 1, and the preparation steps are the same.

[0045] Comparative Example 3: A 3D Printing Ceramic Slurry and Its Preparation Method The only difference is that the mass ratio of "tricalcium phosphate powder, oleic acid, and acid yellow 23 is 1000:1:0.25" in Example 1 is replaced with "tricalcium phosphate powder, oleic acid, and acid yellow 23 is 1000:1:2". The rest of the process is the same as in Example 1, and the preparation steps are the same.

[0046] Example 5: A method for preparing a 3D printed ceramic scaffold. The method for fabricating 3D-printed ceramic scaffolds includes the following steps: S1 was modeled using 10dim software (a porous diamond structure model, wire diameter: 540μm, and the 3D printed ceramic support was modeled as a square with sides of 10mm); printing parameters were set as follows: layer thickness: 50μm, exposure power: 13mW / cm².2 Exposure time: 7s; The slurry prepared in Example 1 is added to the feeding tank of the 3D printer and photopolymerized 3D printing is performed to obtain a blank. The blank is then scraped off with a spatula. S2. The blank obtained in step S1 is centrifuged at a speed of 2000 rpm for 3 min. After centrifugation, the uncured ceramic slurry and the cured 3D printed ceramic support are collected. S3 mixed sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether (AEO-9) at a mass ratio of 17:1 to obtain a cleaning agent. Purified water was added to prepare a cleaning solution with a mass-to-volume ratio of 53 g / L for the cleaning agent and purified water. The cured 3D-printed ceramic scaffold was placed in the cleaning solution and ultrasonically cleaned for 10 min. It was then rinsed with running water for 1 min. Ultrasonic cleaning was performed once with purified water for 5 min. The scaffold was then dried at 70℃ for 3 h to obtain an intermediate 3D-printed ceramic scaffold. S4. Place the intermediate product obtained in step S3 into a crucible, and place the crucible into a high-temperature sintering furnace for sintering. The sintering process parameters are as follows: raise the temperature to 300℃ at a heating rate of 0.3℃ / min and hold for 2 hours; raise the temperature to 600℃ at a heating rate of 0.3℃ / min and hold for 3 hours; raise the temperature to 1100℃ at a heating rate of 3℃ / min and hold for 4 hours; ultrasonically clean with purified water 3 times, and dry at 90℃ for 3 hours to obtain a 3D printed ceramic support.

[0047] Example 6: A method for preparing a 3D printed ceramic scaffold. The only difference is that in step S1 of Example 5, "add the slurry prepared in Example 1 to the feeding tank of the 3D printer" is replaced with "add the slurry prepared in Example 2 to the feeding tank of the 3D printer", and the other steps remain unchanged.

[0048] Example 7: A method for preparing a 3D printed ceramic scaffold. The only difference is that in step S1 of Example 5, "add the slurry prepared in Example 1 into the feeding tank of the 3D printer" is replaced with "add the slurry prepared in Example 3 into the feeding tank of the 3D printer", and the other steps remain unchanged.

[0049] Example 8: A method for preparing a 3D printed ceramic scaffold. The only difference is that in step S3 of Example 5, "mixing sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether (AEO-9) at a mass ratio of 17:1 to obtain a cleaning agent, adding purified water, and preparing a cleaning solution with a mass-volume ratio of 53 g / L for the cleaning agent and purified water" is replaced with "mixing sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether at a mass ratio of 20:1 to obtain a cleaning agent, adding purified water, and preparing a cleaning solution with a mass-volume ratio of 45 g / L for the cleaning agent and purified water", while the other steps remain unchanged.

[0050] Example 9: A method for preparing a 3D printed ceramic scaffold. The only difference is that in step S3 of Example 5, "mixing sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether (AEO-9) at a mass ratio of 17:1 to obtain a cleaning agent, adding purified water, and preparing a cleaning solution with a mass-volume ratio of 53 g / L for the cleaning agent and purified water" is replaced with "mixing sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether at a mass ratio of 15:1 to obtain a cleaning agent, adding purified water, and preparing a cleaning solution with a mass-volume ratio of 60 g / L for the cleaning agent and purified water", while the other steps remain unchanged.

[0051] Example 10: A method for preparing a 3D printed ceramic scaffold. The only difference is that the "modeling size of the 3D printed ceramic support is a square with a side length of 10mm" in step S1 of Example 5 is replaced with "the modeling size of the 3D printed ceramic support is a cuboid with a length of 20mm × width of 20mm × height of 40mm", and the rest of the steps remain unchanged.

[0052] Example 11: A method for preparing a 3D printed ceramic scaffold. The only difference is that the "modeling size of the 3D printed ceramic support is a square with a side length of 10mm" in step S1 of Example 5 is replaced with "the modeling size of the 3D printed ceramic support is a cylinder with a diameter of 5mm and a length of 20mm", and the rest of the steps remain unchanged.

[0053] Comparative Example 4: A method for preparing a 3D-printed ceramic scaffold The only difference is that in step S1 of Example 5, "add the slurry prepared in Example 1 to the feeding tank of the 3D printer" is replaced with "add the slurry prepared in Comparative Example 1 to the feeding tank of the 3D printer", and the other steps remain unchanged.

[0054] Comparative Example 5: A method for preparing a 3D-printed ceramic scaffold The only difference is that in step S1 of Example 5, "add the slurry prepared in Example 1 to the feeding tank of the 3D printer" is replaced with "add the slurry prepared in Comparative Example 2 to the feeding tank of the 3D printer", and the other steps remain unchanged.

[0055] Comparative Example 6: A method for preparing a 3D-printed ceramic scaffold The only difference is that in step S1 of Example 5, "add the slurry prepared in Example 1 to the feeding tank of the 3D printer" is replaced with "add the slurry prepared in Comparative Example 3 to the feeding tank of the 3D printer", and the other steps remain unchanged.

[0056] Comparative Example 7: A method for preparing a 3D-printed ceramic scaffold The method for fabricating 3D-printed ceramic scaffolds includes the following steps: S1 was modeled using 10dim software (a porous diamond structure model, wire diameter: 540μm, and the 3D printed ceramic support was modeled as a square with sides of 10mm); printing parameters were set as follows: layer thickness: 50μm, exposure power: 13mW / cm². 2 Exposure time: 7s; The slurry prepared in Example 1 is added to the feeding tank of the 3D printer and photopolymerized 3D printing is performed to obtain a blank. The blank is then scraped off with a spatula. S2. Sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether (AEO-9) are mixed at a mass ratio of 17:1 to obtain a cleaning agent. Purified water is added to prepare a cleaning solution with a mass-volume ratio of 53 g / L for the cleaning agent and purified water. The blank is placed in the cleaning solution and ultrasonically cleaned for 10 min. It is then rinsed with running water for 1 min. Finally, it is ultrasonically cleaned once with purified water for 5 min. S3 The preform is centrifuged at 2000 rpm for 3 min to obtain a solidified 3D printed ceramic scaffold; it is then dried at 70℃ for 3 h to obtain an intermediate 3D printed ceramic scaffold. S4. Place the intermediate product obtained in step S3 into a crucible, and place the crucible into a high-temperature sintering furnace for sintering. The sintering process parameters are as follows: raise the temperature to 300℃ at a heating rate of 0.3℃ / min and hold for 2 hours; raise the temperature to 600℃ at a heating rate of 0.3℃ / min and hold for 3 hours; raise the temperature to 1100℃ at a heating rate of 3℃ / min and hold for 4 hours; ultrasonically clean with purified water 3 times, and dry at 90℃ for 3 hours to obtain a 3D printed ceramic support.

[0057] Comparative Example 8: A method for preparing a 3D-printed ceramic scaffold Only step S3 of Example 5 is deleted, that is: after completing step S2, the obtained cured 3D printed ceramic bracket is sintered according to step S4 of Example 5.

[0058] Comparative Example 9: A method for preparing a 3D-printed ceramic scaffold The only difference is that in step S3 of Example 5, "mixing sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether (AEO-9) at a mass ratio of 17:1 to obtain a cleaning agent, adding purified water to prepare a cleaning solution with a mass-volume ratio of 53 g / L of cleaning agent to purified water" is replaced with the same mass of purified water, while the other steps remain unchanged.

[0059] Experiment 1: Dimensional Measurement of 3D Printed Ceramic Support Intermediate Product To avoid the impact of the "sintering" process in step S4 on the dimensions of the 3D printed ceramic support, the dimensions of the support before sintering were measured. A digital micrometer was used to measure the dimensions of the intermediate 3D printed ceramic supports (the products of step S3) from Examples 5, 6, 7, Comparative Examples 4, 5, and 6, and to compare their deviations from the design values. The formula for calculating the deviation (1) is: D1 = ΔL / L D ×100%, where D1 is the deviation; △L is the absolute value of the difference between the test value and the design value; L D These are design values; see Table 1 for detailed data.

[0060] Table 1. Dimensional Information of 3D Printed Ceramic Support Intermediate Products

[0061] As can be seen from Table 1, the deviations between the "test values" and "design values" of the length, width, and height of the intermediate 3D printed ceramic supports prepared in Examples 5, 6, and 7 of this invention are all less than 1%, which is significantly lower than the deviations in Comparative Examples 4, 5, and 6. This proves that using the 3D printed ceramic slurry described in this invention can effectively improve the accuracy of 3D printing.

[0062] Experimental Example 2: Porosity Test of 3D Printed Ceramic Scaffold The porosity of the 3D-printed ceramic supports prepared in Examples 5, 8, 9, 7, 8, and 9 was calculated using formula (2), and the deviation (D2) from the design value was analyzed. The formula for calculating porosity is: P = 100% - (d r / d β-TCP ×100%) formula (2).

[0063] Where P is porosity; d r Density of 3D printed ceramic supports; d β-TCP The theoretical density of dense β-tricalcium phosphate is equal to 3.07 g / cm³. 3 .

[0064] The formula for calculating the deviation is: D2 = △P / P D ×100%, where D2 is the deviation; △P is the absolute value of the difference between the test value and the design value; P D The porosity of the various 3D printed ceramic supports mentioned above is shown in Table 2, which represents the design values.

[0065] Table 2 Porosity Information of 3D Printed Ceramic Scaffolds

[0066] As shown in Table 2, the porosity test values ​​of Examples 5, 8, 9, Comparative Examples 7, 8, and 9 all deviate from the design values. This is mainly because the 3D-printed ceramic support undergoes a decrease in size during sintering due to factors such as ceramic powder densification and organic phase removal. Consequently, the volume of the sintered support is smaller than that before sintering, leading to a decrease in the density d of the support. r The porosity P value decreases as the porosity increases. Among these, compared to Comparative Examples 7, 8, and 9, the deviations between the porosity test values ​​and the designed porosity values ​​in Examples 5, 8, and 9 are smaller. This is mainly because the porosity of Example 5 (see the image of the blank) is smaller. Figure 1 As shown; the appearance of the intermediate product of the 3D printed ceramic support is as follows. Figure 2 As shown), Example 8 (Appearance of the intermediate product of 3D printed ceramic bracket as shown) Figure 3 As shown), Example 9 (Appearance of the intermediate product of 3D printed ceramic bracket as shown) Figure 4 The "centrifugation followed by ultrasonic cleaning" process (as shown) can more effectively remove uncured ceramic slurry, from... Figures 2-4 As can be seen, almost no residual yellow uncured ceramic slurry is visible on the surface of the 3D-printed ceramic scaffold intermediate, and the connectivity of the pore structure is good; Comparative Example 7 (appearance of the 3D-printed ceramic scaffold intermediate) Figure 5 As shown), Comparative Example 8 (Appearance of the intermediate 3D printed ceramic support) Figure 6 As shown), Comparative Example 9 (Appearance of the intermediate 3D printed ceramic support) Figure 7 After ultrasonic cleaning, centrifugation or other treatments, the ceramic powder in the residual slurry remains in the pore structure of the support (as shown), causing partial pore blockage. This not only worsens the connectivity of the pore structure of the support, but also leads to a decrease in porosity as the powder in the slurry fills the pores during sintering.

[0067] Experiment 3: CT testing of intermediate 3D-printed ceramic scaffolds and 3D-printed ceramic scaffolds. Micro-CT scans were performed on the intermediate 3D-printed ceramic scaffold prepared in Example 10 and the 3D-printed ceramic scaffold itself. The results showed that the intermediate 3D-printed ceramic scaffold ( Figure 8 No ceramic slurry residue was observed in the pore structure of the 3D-printed ceramic support ( Figure 9 No ceramic slurry residue or residual ceramic powder clogging the pores was observed in the pore structure of the 3D printed ceramic support intermediate and the 3D printed ceramic support. The filament diameter and interconnected porous structure were clearly visible. The results show that the "centrifugation followed by ultrasonic cleaning" process described in this invention can effectively remove residual slurry.

[0068] Experimental Example 4: Bone Repair Effect of 3D Printed Ceramic Scaffold The cylindrical 3D-printed ceramic scaffold prepared in Example 11 was used as a bone repair scaffold and implanted into the femoral ankle defect of a beagle dog to evaluate the bone repair effect of the scaffold. The specific experimental protocol is as follows: Animal Information: Beagle, Age: 16-20 months; Sex: Male.

[0069] Experimental Procedure: Animals were fasted for 8-12 hours and deprived of water for 4 hours preoperatively. Animal weight was measured, and venous access was established in the cephalic vein of the forelimb using a 24G indwelling needle. Animals were divided into three groups: 8 weeks, 12 weeks, and 26 weeks, with three animals in each group. Animals were anesthetized, and 2 mg / kg of salbutamol and 5 μg / kg of dexmedetomidine were administered intramuscularly. Anesthesia was applied to all three groups of animals. 0.2 mg / kg of meloxicam and 2.2 mg / kg of ceftiofur sodium were administered subcutaneously to provide intraoperative analgesia and anti-infection. Hair was shaved from the hip joint to the ankle joint on both thighs. After palpating the patella and lateral trochlear crest, an arc-shaped skin incision was made alongside the patella, extending from the tibial tuberosity to the level of the patella, and then extended upwards at an equal distance. The subcutaneous fascia was incised along the skin incision. Subcutaneous fat and fascia were separated and retracted along with the skin to expose the fascia lata and the lateral fascia of the knee joint. The fascia was cut along the skin incision, the muscles were separated, and the incision was opened using a traction device to fully expose the canine femoral condyle. Lidocaine was dripped for local anesthesia. A 5 mm diameter bone drill was used to drill a hole parallel to the coronal plane and perpendicular to the lateral surface of the femoral condyle, to prepare a cylindrical defect with a diameter of about 5 mm and a depth of about 20 mm. The hole was rinsed and cooled with physiological saline during drilling to prevent overheating and tissue damage. Experimental samples were implanted into the left and right femoral condyles of the animals. The joint capsule, muscles, and subcutaneous tissue were sutured layer by layer using absorbable sutures, and the skin was sutured intermittently using silk sutures. Routine X-rays were taken at 8, 12, and 26 weeks for the surgical sites of the corresponding groups of animals to observe bone formation and bone connection. HE staining was performed on hard tissue sections, and Image J images were collected to analyze the initial implant amount, remaining implant amount, implant cross-sectional area, and new bone formation. The implant degradation rate (MDR) was calculated according to formula (3), and the new bone formation rate (RNBF) of the implant was calculated according to formula (4).

[0070] Implant degradation rate (MDR): Formula (3).

[0071] In the formula: MDR – Implant Degradation Rate; RMV—Residual Implant Amount (the total cross-sectional area of ​​the implant remaining in the tissue, excluding the area inside the pores). IMV – Initial Implant Volume (the total cross-sectional area of ​​the implant before implantation, excluding the area inside the hole).

[0072] New bone formation rate (RNBF) Formula (4).

[0073] In the formula: RNBF—New Bone Formation Rate; NBFV – New bone formation (total area of ​​new bone formed within the cross-section of the implant); MCS – Implant Cross-sectional Area (the total cross-sectional area of ​​the implant before implantation, including the area inside the hole).

[0074] X-ray observation results showed that during the 8 observation periods, the 3D-printed ceramic scaffold implant had a clear outline and a relatively clear boundary with the surrounding bone tissue. The bone tissue gradually filled the gap between them, and the fracture line was partially present. Figure 10 During the 12-cycle observation period, the 3D-printed ceramic scaffold implant showed a clear outline; the boundary between the implant and the surrounding bone tissue was relatively clear, with bone tissue gradually filling the gap between them; a small number of fracture lines remained; and the density of the bone tissue around the implant was similar to that of the overall bone tissue. Figure 11 During the 26-cycle observation period, the 3D-printed ceramic scaffold implant showed a clear outline and a relatively clear boundary with the surrounding bone tissue. The bone tissue basically filled the gap between the two, the fracture line partially disappeared, and the density of the bone tissue around the implant was similar to that of the overall implant. Figure 12 The above experimental results preliminarily indicate that 3D-printed ceramic scaffold implants have bone repair capabilities.

[0075] Histopathological examination of the implantation site revealed the following: During the 8-cycle observation period, minimal infiltration of lymphocytes, macrophages, and giant cells was observed around the implant material; slight microvascularization was observed; fibrous cavities were formed, localized to moderately thick areas, mainly composed of fibroblasts; slight degradation of the implant material was observed; and new bone formation was present. Figure 13 , Figure 14 The average degradation rate of the implant material was 24.48%, and the average new bone formation rate was 23.36%. During the 12-cycle observation period, minimal infiltration of lymphocytes, macrophages, and giant cells was observed around the implant material; mild microvascularization; fibrous cyst formation, localized to moderately thick areas, mainly composed of fibroblasts; implant material degradation; and new bone formation. Figure 15 , Figure 16 The average degradation rate of the implanted material was 30.90%, and the average new bone formation rate was 26.03%. During the 26-cycle observation period, minimal lymphocyte and macrophage infiltration was observed around the implanted material; mild neovascularization; fibrous cyst formation, a localized area mainly composed of fibroblasts; significant degradation of the implanted material; and new bone formation. Figure 17 , Figure 18 The average degradation rate of the implanted material was 45.27%, and the average new bone formation rate was 27.02%.

Claims

1. A method for preparing a 3D-printed ceramic scaffold, characterized in that, Includes the following steps: S1 uses a photopolymerization 3D printing process to print 3D printing ceramic slurry, resulting in a green body composed of an uncured ceramic slurry and a cured 3D printing ceramic support; the 3D printing ceramic slurry includes ceramic powder, photosensitive resin, photoinitiator, dispersant and yellow colorant; S2 Centrifuge the blank obtained in step S1 and collect the separated uncured ceramic slurry and cured 3D printed ceramic support; S3 involves immersing the cured 3D-printed ceramic scaffold in a cleaning solution for ultrasonic cleaning; rinsing with running water; ultrasonically cleaning with purified water; and drying to obtain an intermediate 3D-printed ceramic scaffold product. S4 involves sintering, cleaning, and drying the intermediate 3D printed ceramic support obtained in step S3 to obtain the final product.

2. The method for preparing a 3D-printed ceramic scaffold according to claim 1, characterized in that, The ceramic powder is any one or more of hydroxyapatite, biphasic calcium phosphate, calcium carbonate, calcium silicate, and calcium phosphate.

3. The method for preparing a 3D-printed ceramic scaffold according to claim 1, characterized in that, The dispersant is oleic acid, linoleic acid, or oleic acid amine; the yellow colorant is curcumin, acid yellow 23, or β-carotene.

4. The method for preparing a 3D-printed ceramic scaffold according to any one of claims 1-3, characterized in that, The mass ratio of the ceramic powder, dispersant, and yellow colorant is 1000:(0.8-1.2):(0.05-1).

5. The method for preparing a 3D-printed ceramic scaffold according to any one of claims 1-4, characterized in that, The method for preparing the 3D printing ceramic slurry includes the following steps: (1) Mix the dispersant and anhydrous ethanol, stir well, and prepare solution A; (2) Mix the ceramic powder, yellow colorant and solution A obtained in step (1), add anhydrous ethanol, and ball mill the mixture for the first time. Then dry the mixture to obtain yellow powder. (3) Mix the photosensitive resin with the yellow powder obtained in step (2), perform a second ball milling, add the photoinitiator, and perform a third ball milling to obtain a mixture of materials and balls; (4) Centrifuge the mixture of pellets obtained in step (3) to obtain 3D printing ceramic slurry.

6. The method for preparing a 3D-printed ceramic scaffold according to claim 1, characterized in that, In step S3, the ratio of the cured 3D printed ceramic support to the cleaning solution is 1g:(2-20)mL; the cleaning solution is composed of a cleaning agent and purified water; the cleaning agent is composed of sodium dodecylbenzenesulfonate and fatty alcohol polyoxyethylene ether; the mass-volume ratio of the cleaning agent to purified water in the cleaning solution is 45-60g / L; the mass ratio of sodium dodecylbenzenesulfonate to fatty alcohol polyoxyethylene ether in the cleaning agent is (15-20):

1.

7. The method for preparing a 3D-printed ceramic scaffold according to claim 1, characterized in that, In step S4, the sintering process parameters are as follows: the temperature is raised to 250-350℃ at a heating rate of 0.2-1℃ / min and held for 1-3 hours; the temperature is raised to 550-700℃ at a heating rate of 0.2-1℃ / min and held for 2-4 hours; the temperature is raised to 1000-1200℃ at a heating rate of 2-5℃ / min and held for 4-6 hours.

8. A 3D printed ceramic scaffold prepared by the preparation method according to any one of claims 1-7.

9. The application of the 3D-printed ceramic scaffold according to claim 8 in bone fillers, bone scaffolds, or as scaffolds for in vitro cell culture.

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