Hydroxyapatite biological ceramic aerogel with directional hole structure as well as preparation method and application of hydroxyapatite biological ceramic aerogel

Abstract

The invention relates to the technical field of ceramic aerogel, in particular to hydroxyapatite biological ceramic aerogel with a directional hole structure as well as a preparation method and application of the hydroxyapatite biological ceramic aerogel. The preparation method comprises the following steps: firstly, adding hydroxyapatite particles, a sintering aid and a binder into a water solvent according to a certain mass ratio to prepare aerogel ink; and secondly, filling the ink into an extrusion needle tube of a direct-writing 3D printing technology, and carrying out customized printing on hydroxyapatite aerogel on a liquid nitrogen cooled copper plate by adopting an ice template method as an assistance. After freeze drying and sintering, the biological ceramic aerogel with the directional hole structure on the micro scale is finally obtained. The oriented pore biological ceramic aerogel has excellent mechanical properties and biocompatibility, and has good prospects in the fields of biological scaffolds, bone tissue engineering, biosensor substrates and the like. The method for preparing the hydroxyapatite biological ceramic aerogel by using the ice template method to assist the 3D printing technology is low in cost, simple to operate and wide in application range, and has great application potential.

Description

Technical Field

[0001] The invention relates to the technical field of ceramic aerogels, and in particular to a hydroxyapatite bioceramic aerogel with a directional pore structure, a preparation method and an application thereof. Background Art

[0002] Bioceramic aerogels are highly porous structural materials, usually composed of biocompatible ceramic components (such as hydroxyapatite). They are lightweight, high specific surface area and good bioactivity, can support cell growth and tissue regeneration, and are widely used in fields such as bone repair and tissue engineering. The demand for high-performance bioceramic aerogels is growing. At present, a major challenge in the development of bioceramic aerogels is to design, quickly and cost-effectively manufacture bioceramic aerogels with excellent mechanical properties and biocompatibility.

[0003] 3D printing technology (also known as additive manufacturing) is a method of manufacturing structural materials with complex geometric shapes by stacking raw materials layer by layer based on digital 3D models. It has the advantages of arbitrary shaping, rapid prototyping, and high production efficiency. 3D-printed bioceramic aerogels not only have complex geometric shapes and excellent mechanical properties, which can meet various personalized customization needs, but can also be produced on demand anywhere. Therefore, 3D printing technology provides huge opportunities for the development of bioceramic aerogels in fields such as bone tissue repair and regenerative medicine.

[0004] In order to further improve the mechanical properties and biocompatibility of bioceramic aerogels, the design of highly arranged microscopic directional pore structures has great potential in enhancing the mechanical properties of bioceramic aerogels and promoting bone cell growth. 3D printing assisted by ice template method can meet the efficient production and personalized design of bioceramic aerogels, and can effectively optimize the biocompatibility of bioceramic aerogels, but the preparation of microscopic complex structures requires higher control precision and higher requirements for raw materials, which increases the cost and difficulty of manufacturing. Summary of the invention

[0005] The purpose of the present invention is to address the problems existing in the background technology and propose a method for preparing hydroxyapatite bioceramic aerogel with a directional pore structure, and to use an ice template method to assist 3D printing technology to prepare the bioceramic aerogel; the 3D printing method for preparing bioceramic aerogel proposed in the present invention is novel, simple in process, and low in cost, and can realize the arbitrary multi-scale macrostructure and microstructure of the bioceramic aerogel, which has important application value for the development of bioceramic aerogel.

[0006] The technical solution of the present invention is a hydroxyapatite bioceramic aerogel with a directional pore structure, which uses hydroxyapatite bioceramic particles as raw materials and uses ice template method as an auxiliary to prepare bioceramic aerogel with a controllable directional pore structure based on 3D printing technology;

[0007] The prepared bioceramic aerogel has good compressive resistance and biocompatibility.

[0008] Preferably, the shape, quantity and size of the directional hole structure are adjustable.

[0009] A method for preparing a directional pore structured hydroxyapatite bioceramic aerogel, the preparation of the above-mentioned bioceramic aerogel comprising the following specific steps:

[0010] S1. Prepare raw materials; mix hydroxyapatite bioceramic particles, sintering aid, binder and solvent in a certain mass ratio, and stir to prepare printing ink;

[0011] S2, loading the printing ink into an ink direct writing 3D printer, and performing customized printing on a copper plate immersed in liquid nitrogen;

[0012] S3, freeze-drying the semi-finished product obtained in step S2;

[0013] S4, placing the product in step S3 into a tubular furnace, increasing the temperature in a gradient manner, and sintering at a high temperature for a period of time to obtain a bioceramic aerogel with a directional pore structure.

[0014] Preferably, the bioceramic particle material in step S1 is selected from one or more combinations of hydroxyapatite, tricalcium phosphate, bioactive glass, β-tricalcium phosphate, and alumina.

[0015] Preferably, the sintering aid in step S1 is selected from one or more combinations of zinc oxide, aluminum oxide, zirconium oxide, calcium fluoride, sodium borate, calcium aluminate, quartz, and lithium zirconate.

[0016] Preferably, in step S1, the binder is selected from one or more combinations of cellulose nanofibers, sodium alginate, chitosan, polyvinyl alcohol, carrageenan, guar gum, xanthan gum, gum arabic, pectin, gelatin, lignin, and epoxy resin; and the solvent is water.

[0017] Preferably, in step S1, the mass ratio of the bioceramic particles, the sintering aid and the adhesive is 6-10:1-3:1-3, and the ratio of the added solvent is 3-10 ml / g; during the stirring in step S1, a stirrer is used to stir for 1.5-3 hours to fully mix.

[0018] Preferably, the step S2 is prepared by direct ink writing 3D printing;

[0019] The raw materials in step S1 are loaded into an ink direct writing 3D printer as printing ink, and the ice template method is used as an auxiliary to custom print the bioceramic aerogel on the cooled substrate;

[0020] Among them, the nozzle diameter of the ink direct writing 3D printer in S2 is 400-1600um, the printing pressure is 10-120psi, and the needle speed is 1-50mm / s;

[0021] The shapes of bioceramic aerogels printed by the ink direct writing 3D printer in S2 can be customized, including circular grids, diamond grids or pyramids;

[0022] The temperature of the substrate in S2 ranges from -196°C to -5°C, and the substrate material is copper, iron, stainless steel, alloy or a combination thereof.

[0023] Preferably, the freeze-drying time in step S3 is 8 to 24 hours, and the freeze-drying temperature is -20 to -60°C; the temperature gradually increased to in step S4 is 500-1800°C, and the high-temperature sintering time is 2-30 hours.

[0024] A directional pore structured hydroxyapatite bioceramic aerogel is used in bone tissue repair, drug delivery, and biosensors, and is prepared using the above method;

[0025] The prepared bioceramic aerogel acts as a biological scaffold; its microscopic directional pore structure is used for bone cell attachment and proliferation, and promotes bone cell growth and nutrient exchange.

[0026] Compared with the prior art, the present invention has the following beneficial technical effects:

[0027] 1. Excellent mechanical properties and biocompatibility: Compared with traditional bioceramic aerogels, the method of preparing bioceramic aerogels using ice template assisted 3D printing technology proposed in the present invention can achieve good compressive resistance and optimize biocompatibility.

[0028] 2. Simplified process and low cost: The present invention provides a 3D printing method using an ice template method, which has a simple process, low cost and is suitable for mass production.

[0029] 3. Optimized microstructure: The ice template method is used to prepare the microporous structure of bioceramic aerogel, which promotes the proliferation and growth of bone cells.

[0030] 4. Customizable macrostructure: The bioceramic aerogel prepared by the method of the present invention has an adjustable macrostructure, which can further promote the application of bioceramic aerogel in the biomedical field through personalized design.

[0031] 5. Adjustable microporous structure: The number and size of directional pores can be adjusted by adjusting the concentration of ink. The lower the ink concentration and the higher the water content, the more and larger the number of directional pores will be. Controlling the temperature gradient of the ice template method can adjust the arrangement of directional pores. The larger the temperature gradient, the more orderly the pore arrangement. The bioceramic aerogel prepared by the method of the present invention has an adjustable directional pore structure, which can change the number and size of the directional pore structure distribution.

[0032] 6. Wide applicability: The method for preparing hydroxyapatite bioceramic aerogel proposed in the present invention is also applicable to the preparation of other bioceramic systems. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Flow chart for the preparation of 3D printing of hydroxyapatite bioceramic aerogel;

[0034] Figure 2 is the rheological diagram of hydroxyapatite bioceramic aerogel;

[0035] Figure 3 A demonstration of 3D printed hydroxyapatite bioceramic aerogel;

[0036] Figure 4 This is a microscopic SEM image of the cross section of the 3D printed directional pore structure hydroxyapatite bioceramic aerogel before sintering;

[0037] Figure 5 This is a microscopic SEM image of the cross section of the 3D printed directional pore structure hydroxyapatite bioceramic aerogel after sintering;

[0038] Figure 6 Compression properties of hydroxyapatite bioceramic aerogel. DETAILED DESCRIPTION

[0039] Example 1

[0040] A 3D printed directional pore structure hydroxyapatite bioceramic aerogel, the preparation method of which comprises the following steps:

[0041] 1. Mix hydroxyapatite particles, alumina particles, sodium alginate and water in a mass ratio of 5:2:3:3, stir for 4 hours until the mixture is uniform, and prepare printing ink.

[0042] 2. Load the printing ink into a direct-write 3D printer with a nozzle diameter of 600 μm, a printing pressure of 10 psi, and a needle speed of 25 mm / s, and perform ice template-assisted printing on a copper plate at -75°C.

[0043] 3. The printed bioceramic aerogel was freeze-dried for 12 h at -30 °C.

[0044] 4. Place the bioceramic aerogel in a tubular furnace, gradually increase the temperature to 1300°C, and sinter for 2 hours.

[0045] 5. Obtain directional pore structured hydroxyapatite bioceramic aerogel.

[0046] Example 2

[0047] A 3D printed directional pore structure hydroxyapatite bioceramic aerogel, the preparation method of which comprises the following steps:

[0048] 1. Mix hydroxyapatite particles, calcium fluoride particles, xanthan gum and water in a mass ratio of 7:3:2:3, stir for 5 hours until the mixture is uniform, and prepare printing ink.

[0049] 2. Load the printing ink into a direct-write 3D printer with a nozzle diameter of 600 μm, a printing pressure of 20 psi, and a needle speed of 30 mm / s, and perform ice template-assisted printing on a copper plate at -50 °C.

[0050] 3. The printed bioceramic aerogel was freeze-dried for 10 h at -40 °C.

[0051] 4. Place the bioceramic aerogel into a tubular furnace, gradually increase the temperature to 1350°C, and sinter for 4 hours.

[0052] 5. Obtain directional pore structured hydroxyapatite bioceramic aerogel.

[0053] Example 3

[0054] A 3D printed directional pore structure bioceramic aerogel, the preparation method of which comprises the following steps:

[0055] 1. Mix bioactive glass particles, zirconium oxide particles, chitosan and water in a mass ratio of 6:1:2:2, stir for 2 hours until the mixture is uniform, and prepare printing ink.

[0056] 2. Load the printing ink into a direct-write 3D printer with a nozzle diameter of 400 μm, a printing pressure of 15 psi, and a needle speed of 30 mm / s, and perform ice template-assisted printing on a copper plate at -50 °C.

[0057] 3. The printed bioceramic aerogel was freeze-dried for 15 h at -35 °C.

[0058] 4. Place the bioceramic aerogel into a tubular furnace, gradually increase the temperature to 1400°C, and sinter for 2.5 hours.

[0059] 5. Obtain bioceramic aerogel with directional pore structure.

[0060] Example 4

[0061] A bioceramic aerogel with a directional pore structure, the preparation method of which comprises the following steps:

[0062] 1. Mix alumina particles, zirconium oxide particles, sodium alginate and water in a mass ratio of 6:1.5:1.5:2, stir for 3 hours until the mixture is uniform, and prepare printing ink.

[0063] 2. Load the printing ink into a direct-write 3D printer with a nozzle diameter of 400 μm, a printing pressure of 10 psi, and a needle speed of 20 mm / s, and perform ice template-assisted printing on a copper plate at -65°C.

[0064] 3. The printed bioceramic aerogel was freeze-dried for 12 h at -40 °C.

[0065] 4. Place the bioceramic aerogel into a tubular furnace, gradually increase the temperature to 1350°C, and sinter for 2 hours.

[0066] 5. Obtain bioceramic aerogel with directional pore structure.

[0067] Example 5

[0068] A bioceramic aerogel with a directional pore structure, the preparation method of which comprises the following steps:

[0069] 1. Mix tricalcium phosphate particles, quartz particles, guar gum and water in a mass ratio of 8:3:2:2, stir for 2 hours until the mixture is uniform, and prepare printing ink.

[0070] 2. Load the printing ink into a direct-write 3D printer with a nozzle diameter of 400 μm, a printing pressure of 20 psi, and a needle speed of 15 mm / s, and perform ice template-assisted printing on a copper plate at -70 °C.

[0071] 3. The printed bioceramic aerogel was freeze-dried for 18 h at -35 °C.

[0072] 4. Place the bioceramic aerogel into a tubular furnace, gradually increase the temperature to 1300°C, and sinter for 2.5 hours.

[0073] 5. Obtain bioceramic aerogel with directional pore structure.

[0074] Example 6

[0075] A bioceramic aerogel with a directional pore structure, the preparation method of which comprises the following steps:

[0076] 1. Mix tricalcium phosphate particles, zinc oxide particles, polyvinyl alcohol and water in a mass ratio of 7:1.5:2:3, stir for h until the mixture is uniform, and prepare printing ink.

[0077] 2. Load the printing ink into a direct-write 3D printer with a nozzle diameter of 350 μm, a printing pressure of 18 psi, and a needle speed of 20 mm / s, and perform ice template-assisted printing on a copper plate at -75°C.

[0078] 3. The printed bioceramic aerogel was freeze-dried for 15 h at -40 °C.

[0079] 4. Place the bioceramic aerogel into a tubular furnace, gradually increase the temperature to 1350°C, and sinter for 2 hours.

[0080] 5. Obtain bioceramic aerogel with directional pore structure.

[0081] Comparative Example 1

[0082] The bioceramic aerogels prepared in Examples 1-6 were tested for performance.

[0083] Rheological test steps:

[0084] First, the bioceramic aerogel ink prepared in Examples 1-6 was placed in a rheometer to test the viscosity of the ink, the stability of the ink at different frequencies, and the rheological properties of the ink under different shear stresses.

[0085] Mechanical testing steps:

[0086] The bioceramic aerogel was placed on the platform of a universal testing machine and compressed axially and radially respectively. The slope of the ceramic aerogel in the elastic strain state was then taken as the compression modulus. The test results were recorded three times and the average value was taken. Finite element analysis (FEA) was further carried out using finite element software to study the strain behavior of the ceramic aerogel in the compression state.

[0087] The test results are shown in the following table:

[0088] Table 1 Example parameters and bioceramic aerogel properties

[0089]

[0090] Analysis of the experimental data in Table 1 shows that the bioceramic aerogel can be continuously and stably printed by rheological, mechanical and biocompatibility tests, and has excellent mechanical properties and biocompatibility. This shows that the bioceramic aerogel prepared by this method can achieve efficient, low-cost and customized printing preparation while maintaining good mechanical properties and biocompatibility.

[0091] like Figure 2 As shown, the bioceramic aerogel prepared by the method of the present invention can be printed and prepared continuously and stably, which is conducive to industrial production.

[0092] like Figure 3As shown, 3D printed bioceramic aerogels can be customized in shape and size according to needs to improve adaptability.

[0093] like Figure 4 , Figure 5 as well as Figure 6 As shown in the figure, bioceramic aerogel has high porosity and directional pore structure, which is conducive to the attachment and proliferation of bone cells; specifically, the cultured cells can all attach to the porous structure, and the number of cell proliferation is more than twice the original number, while the non-directional bioceramic aerogel directly written and printed with normal ink has a relatively low porosity, and nearly half of the cells cannot attach to the pore structure, and the number of cell proliferation is only 1.2 times the original number; at the same time, the directional pores can promote the growth of bone cells and the exchange of nutrients, thereby improving the bone repair and regeneration effect. This good mechanical property is also conducive to the bioceramic aerogel acting as a biological scaffold.

[0094] The embodiments of the present invention are described in detail above with reference to the accompanying drawings, but the present invention is not limited thereto, and various changes can be made within the knowledge scope of technicians in the relevant technical field without departing from the purpose of the present invention.

Claims

1. A directional pore structure hydroxyapatite bioceramic aerogel, characterized in that: Using hydroxyapatite bioceramic particles as raw materials and ice template method as an aid, bioceramic aerogels with adjustable directional pore structures were prepared based on 3D printing technology. The prepared bioceramic aerogel has good compressive resistance and biocompatibility.

2. The directional pore structured hydroxyapatite bioceramic aerogel according to claim 1, characterized in that: The shape, quantity and size of the directional pore structure can be adjusted by adjusting the directional freezing rate, freezing temperature and concentration of the printing ink respectively.

3. A method for preparing a directional pore structured hydroxyapatite bioceramic aerogel, comprising preparing the bioceramic aerogel according to any one of claims 1 to 2, characterized in that: The specific steps include: S1. Prepare raw materials; mix hydroxyapatite bioceramic particles, sintering aid, binder and solvent in a certain mass ratio, and stir to prepare printing ink; S2, loading the printing ink into an ink direct writing 3D printer, and performing customized printing on a copper plate immersed in liquid nitrogen; S3, freeze-drying the semi-finished product obtained in step S2; S4, placing the product in step S3 into a tubular furnace, increasing the temperature in a gradient manner, and sintering at a high temperature for a period of time to obtain a bioceramic aerogel with a directional pore structure.

4. The method for preparing a directional pore structured hydroxyapatite bioceramic aerogel according to claim 3, characterized in that: In step S1, the bioceramic particle material is selected from one or more combinations of hydroxyapatite, tricalcium phosphate, bioactive glass, β-tricalcium phosphate, and alumina.

5. The method for preparing a directional pore structured hydroxyapatite bioceramic aerogel according to claim 3, characterized in that: In step S1, the sintering aid is selected from one or more combinations of zinc oxide, aluminum oxide, zirconium oxide, calcium fluoride, sodium borate, calcium aluminate, quartz, and lithium zirconate.

6. The method for preparing a directional pore structured hydroxyapatite bioceramic aerogel according to claim 3, characterized in that: In step S1, the adhesive is selected from one or more combinations of cellulose nanofibers, sodium alginate, chitosan, polyvinyl alcohol, carrageenan, guar gum, xanthan gum, gum arabic, pectin, gelatin, lignin, and epoxy resin; and the solvent is water.

7. A method for preparing a directional pore structured hydroxyapatite bioceramic aerogel according to any one of claims 3 to 6, characterized in that: In step S1, the mass ratio of bioceramic particles, sintering aid and adhesive is 6-10:1-3:1-3, and the ratio of added solvent is 3-10 ml / g; during stirring in step S1, a stirrer is used to stir for 1.5-3 hours to fully mix.

8. The method for preparing a directional pore structured hydroxyapatite bioceramic aerogel according to claim 7, characterized in that: Prepared by direct ink writing 3D printing in step S2; The raw materials in step S1 are loaded into an ink direct writing 3D printer as printing ink, and the ice template method is used as an auxiliary to custom print the bioceramic aerogel on the cooled substrate; Among them, the nozzle diameter of the ink direct writing 3D printer in S2 is 400-1600um, the printing pressure is 10-120psi, and the needle speed is 1-50mm / s; The shapes of bioceramic aerogels printed by the ink direct writing 3D printer in S2 can be customized, including circular grids, diamond grids or pyramids; The temperature of the substrate in S2 ranges from -196°C to -5°C, and the substrate material is copper, iron, stainless steel, alloy or a combination thereof.

9. The method for preparing a directional pore structured hydroxyapatite bioceramic aerogel according to claim 7, characterized in that: In step S3, the freeze drying time is 8 to 24 hours, and the freeze drying temperature is -20 to -60°C; in step S4, the temperature gradually increased to is 500-1800°C, and the high temperature sintering time is 2-30 hours.

10. Application of directional pore structured hydroxyapatite bioceramic aerogel in bone tissue repair, drug delivery, and biosensor, characterized in that: Prepared by the method according to any one of claims 3 to 9; The prepared bioceramic aerogel acts as a biological scaffold; its microscopic directional pore structure is used for bone cell attachment and proliferation, and promotes bone cell growth and nutrient exchange.

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