A mechanically reinforced 3D printed calcium phosphate ceramic scaffold and its preparation method and application

Abstract

The present invention discloses a mechanically reinforced 3D printed calcium phosphate ceramic scaffold and a preparation method thereof. The present invention also discloses the use of the above-mentioned mechanically reinforced 3D printed calcium phosphate ceramic scaffold in the preparation of bone defect repair materials. Different from the traditional reinforcement method of adding second-phase whiskers, the present invention introduces metal salts that induce the growth of calcium phosphate grains into the photocurable 3D printing slurry, effectively avoiding the influence of the added whiskers on the fluidity of the printing slurry, and then performs normal printing and molding, and finally regulates the directional growth of calcium phosphate grains in the sintering process to form a mechanically reinforced whisker structure, which significantly improves the mechanical properties of the material on the basis of ensuring that calcium phosphate can be 3D printed and customized, biologically active, and safe; at the same time, the metal salt that regulates the growth of calcium phosphate grains also has biological functions, which can further enhance the biological activity of calcium phosphate ceramics.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a mechanically reinforced 3D printed calcium phosphate ceramic scaffold and a preparation method and application thereof. Background Art

[0002] Repair of large bone defects is a medical problem that has long plagued clinical practice. Existing treatment methods have obvious shortcomings and can no longer meet patients' ultimate demand for restoration. The characteristic of large bone defects is that the body cannot heal itself, which determines that the repair material must have sufficient bioactivity to promote bone tissue growth. In addition, the repair material must have a certain mechanical strength to maintain bone stability and ensure new bone growth. Among bioactive bone repair materials, calcium phosphate ceramics have excellent osteoconduction and osteoinduction, showing great application prospects. However, the mechanical strength of porous calcium phosphate ceramics is too low, just like the short board in the barrel effect, which severely limits the scope of application. At present, it is mostly used as filling or surface coating materials in clinical practice.

[0003] The current difficulty in the research of porous calcium phosphate ceramic reinforcement lies in how to balance biological activity and mechanical strength. The improvement of the mechanical properties of calcium phosphate ceramics cannot be at the expense of biological activity, otherwise it will lose its greatest competitive advantage. Whisker reinforcement has achieved remarkable results in the reinforcement and toughening of composite materials. The whisker structure in the material can achieve mechanical strengthening by blocking the expansion of cracks. Whisker reinforcement technology has been successfully applied in the reinforcement research of bioceramics, but there are two major technical problems through the addition of whiskers: 1) The fusion of whiskers and the matrix is ​​poor, and the improvement of mechanical strength is limited. 2) It affects the porous structure of bioceramics, making it difficult to carry out customized production. Summary of the invention

[0004] The purpose of the present invention is to solve the problems in the prior art that the addition of whiskers to bioceramics leads to poor fusion between the whiskers and the bioceramic matrix, poor effect on improving mechanical strength, and difficulty in customized production, and to provide a mechanically reinforced 3D printed calcium phosphate ceramic scaffold and its preparation method and application.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows: a method for preparing a mechanically reinforced 3D printed calcium phosphate ceramic scaffold, comprising the following steps:

[0006] S1. After fully mixing polyurethane acrylate, polyethylene glycol diacrylate and BYK-2155, add calcium phosphate ceramic raw materials accounting for 60% of the total mass of the slurry and continue ball milling for 15 hours; then add whisker growth inducing components and continue ball milling for 2 hours; add TPO of 1% of the organic phase mass and continue ball milling for 2 hours, and after degassing, 3D printing slurry can be obtained;

[0007] S2, adding 3D printing slurry into the printer, and at the same time importing the 3D model of the porous scaffold into the printer, and preparing the porous scaffold by using light-curing 3D printing technology;

[0008] S3. Debinding and sintering the porous scaffold to obtain a mechanically reinforced 3D printed calcium phosphate ceramic scaffold.

[0009] Preferably, the polyurethane acrylate, polyethylene glycol diacrylate and BYK-2155 are mixed in a mass ratio of 50:15:1.

[0010] Preferably, the calcium phosphate ceramic raw material is one of tricalcium phosphate, hydroxyapatite, biphasic calcium phosphate, tetracalcium phosphate, and monocalcium phosphate.

[0011] Preferably, the whisker growth inducing component is one of calcium sulfate, calcium sulfate hydrate, sodium chloride, potassium chloride, calcium chloride, magnesium phosphate, calcium fluoride, and strontium sulfate.

[0012] Preferably, the added amount of the whisker growth inducing component is 10%-30% of the mass of the calcium phosphate ceramic raw material.

[0013] Preferably, in S3, the porous scaffold is cleaned with anhydrous ethanol and naturally dried before degreasing and sintering, and the heating curve is: heating to 300°C at 5°C / min and keeping warm for 6 hours, then heating to 600°C at 5°C / min and keeping warm for 2 hours, then heating to 900°C at 5°C / min and keeping warm for 5-20 hours, then heating to 1150°C at 5°C / min and keeping warm for 2 hours. After the end, it is naturally cooled to room temperature to obtain a mechanically strengthened 3D printed calcium phosphate ceramic scaffold.

[0014] The present invention also provides a mechanically reinforced 3D printed calcium phosphate ceramic scaffold prepared by the above method and its application in preparing bone defect repair materials.

[0015] The beneficial effects of the present invention are:

[0016] (i) The present invention generates hydroxyapatite whiskers in situ inside the calcium phosphate ceramic matrix. The in situ generated whiskers have very good fusion with the matrix, thereby significantly improving the mechanical properties of the porous calcium phosphate scaffold.

[0017] (ii) The metal salt for regulating the growth of calcium phosphate grains in the present invention also has biological functions and can significantly enhance the biological activity of calcium phosphate ceramics.

[0018] (III) The present invention is different from the traditional reinforcement method of adding second phase whiskers. The present invention introduces metal salts that induce the growth of calcium phosphate grains into the photocurable 3D printing slurry, effectively avoiding the influence of the added whiskers on the fluidity of the printing slurry, and then performs normal printing and molding. Finally, during the sintering process, the directional growth of calcium phosphate grains is regulated to form a mechanically strengthened whisker structure, thereby realizing personalized customized production of 3D printing while ensuring the biological activity and safety of calcium phosphate. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The microscopic morphology of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1, wherein Figure 1 -a is the macroscopic porous structure of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1; 1-b is the microscopic structure of the pure hydroxyapatite scaffold; 1-c is the microscopic structure of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1;

[0020] Figure 2 The physical structure of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1;

[0021] Figure 3 The mechanical strength curve of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1-3;

[0022] Figure 4 This is a microstructure diagram of the 3D printed calcium phosphate ceramic scaffold prepared in Example 4;

[0023] Figure 5 This is a degradation rate curve of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1-3;

[0024] Figure 6 This is a graph showing the active calcium ion release rate of the 3D printed calcium phosphate ceramic scaffold prepared in Example 1-3;

[0025] Figure 7 This is a microscopic morphology of the 3D printed calcium phosphate ceramic scaffold prepared in Example 5. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.

[0027] Example 1

[0028] 1. Prepare the photocurable ceramic 3D printing slurry

[0029] (1) Mix polyurethane acrylate, polyethylene glycol diacrylate and BYK-2155 in a mass ratio of 50:15:1. (2) Mix 60% of the total mass of hydroxyapatite (HAP) powder with the above-mentioned mixture and add it to a planetary ball mill, and mill it at a speed of 240r / min for 15h. (3) Add 30% of the mass of hydroxyapatite powder dihydrate (CaSO4·2H2O) and continue grinding for 2h. (4) Add 1% of the mass of organic phase TPO and continue ball milling for 2h. (5) Separate the slurry and grinding balls, and use a degasser to degas to obtain the printing slurry.

[0030] 2. Add 3D printing slurry into the printer, import the designed 3D model of the porous scaffold into the printer, and use light-curing 3D printing technology to print and prepare the porous scaffold.

[0031] 3. Debinding and sintering

[0032] (1) Clean the printed bracket with anhydrous ethanol and dry it naturally. (2) Place the bracket in a muffle furnace for degreasing and sintering. The basic heating curve is as follows: heat to 300℃ at 5℃ / min and keep it for 6h, then heat to 600℃ at 5℃ / min and keep it for 2h, then heat to 900℃ at 5℃ / min and keep it for 10h, then heat to 1150℃ at 5℃ / min and keep it for 2h. After cooling to room temperature, a mechanically enhanced 3D printed calcium phosphate ceramic bracket can be obtained.

[0033] The microscopic morphology of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment is shown in the attached Figure 1 As shown in the figure, 3D printing technology is used to ensure the personalized shape and macroscopic porous structure of the scaffold ( Figure 1 -a); Compared with the microstructure of pure hydroxyapatite scaffold (1-b), the calcium sulfate added in this embodiment can induce the directional growth of hydroxyapatite grains into prismatic whiskers during sintering ( Figure 1 -c), thereby achieving the effect of mechanical enhancement. The physical structure of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment is as follows Figure 2 As shown; the compressive strength comparison of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment is Figure 3 As shown in the 30SH curve, compared with the pure hydroxyapatite scaffold, the mechanical strength of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment is increased by 5 times. Figure 5 As shown in the 30% curve, the degradation rate of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment is significantly improved compared with pure HA ceramics. The release rate of active calcium ions of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment is also significantly improved compared with HA ceramics, such as Figure 6 The 30% curve is shown in the figure.

[0034] Example 2

[0035] The preparation method of this embodiment is consistent with that of embodiment 1, except that the whisker growth inducing component in this embodiment is calcium sulfate (CaSO4), and the mass ratio of hydroxyapatite (HAP) to calcium sulfate (CaSO4) is 9:1; a DLP printing device is used for printing and forming, and a mechanically reinforced 3D printed calcium phosphate ceramic scaffold is obtained after degreasing and sintering. Compared with embodiment 1, this embodiment reduces the content of calcium sulfate, and the whisker structure in the final ceramic matrix is ​​less, and the mechanical strength is improved by more than 4 times compared with the pure hydroxyapatite scaffold (such as Figure 3 However, compared with Example 1, the degradation rate of the composite ceramic scaffold prepared in this example is slower. Figure 5 As shown in the 10% curve, its degradation rate is close to that of pure HA ceramics. This material is suitable for preparing materials for bone defects that require a longer repair time.

[0036] Example 3

[0037] The preparation method of this embodiment is consistent with that of embodiment 1, except that the raw material of calcium phosphate ceramic in this embodiment is biphasic calcium phosphate (BCP); the whisker growth inducing component is calcium sulfate (CaSO4), and the mass ratio of biphasic calcium phosphate (BCP) to calcium sulfate (CaSO4) is 8:2; a DLP printing device is used for printing and forming, and a mechanically reinforced 3D printed calcium phosphate ceramic bracket is obtained after degreasing and sintering. The mechanical strength of the 3D printed calcium phosphate ceramic bracket prepared in this embodiment is shown in FIG. Figure 3 As shown in the curve of 20SH, the degradation rate is Figure 5 As shown in the curve of 20%, the release rate of active calcium ions is Figure 6 As shown in the 20% curve, the mechanical strength, degradation rate and active calcium ion release rate of the 3D printed calcium phosphate ceramic scaffold prepared in this embodiment are between Example 1 and Example 2. Since the calcium phosphate ceramic raw material used in this embodiment is biphasic calcium phosphate, biphasic calcium phosphate has better biological activity and degradation rate than hydroxyapatite. In addition, the whisker structure induced by calcium sulfate can greatly improve the mechanical strength of biphasic calcium phosphate ceramics and broaden its application range. In summary, the obtained ceramic scaffold has a faster degradation rate and better biological activity and mechanical support, and is suitable for the preparation of bone defect repair materials that require a faster degradation rate.

[0038] Example 4

[0039] The preparation method of this embodiment is consistent with that of embodiment 1, except that, in this embodiment, the whisker growth inducing component is sodium chloride (NaCl), and the mass ratio of hydroxyapatite (HAP) to sodium chloride (NaCl) is 8:2; a DLP printing device is used for printing and forming, and after degreasing and sintering to generate whiskers, the ceramic bracket is fully washed with Up water to remove the sodium chloride in the matrix, and a mechanically strengthened 3D printed calcium phosphate ceramic bracket is obtained, and its microstructure is as follows: Figure 4 Compared with Examples 1-3, the whisker inducing component used in this embodiment is sodium chloride. In this embodiment, sodium chloride only plays a role in inducing whisker growth and does not participate in subsequent bone repair. Therefore, it does not significantly increase the calcium ion release and degradation rate of hydroxyapatite ceramics. After implantation in the body, the physical and chemical properties are more stable.

[0040] Example 5

[0041] The preparation method of this embodiment is consistent with that of embodiment 4, except that, in this embodiment, the whisker growth inducing component is strontium sulfate, and the mass ratio of hydroxyapatite to strontium sulfate is 7:3; a DLP printing device is used for printing and forming, and after degreasing and sintering to generate whiskers, a mechanically reinforced 3D printed calcium phosphate ceramic scaffold is obtained, and its microscopic morphology is as follows Figure 7 The strontium sulfate in this embodiment not only plays a role in inducing whisker growth, but also provides active strontium ions to promote osteogenesis and accelerate the process of bone repair, ultimately achieving dual optimization of material biological activity and mechanical strength.

[0042] The specification and drawings of the present invention are considered to be illustrative rather than restrictive. On the basis of the present invention, those skilled in the art can make some substitutions and modifications to some of the technical features according to the disclosed technical content without creative labor, all of which are within the protection scope of the present invention.

Claims

1. A method for preparing a mechanically reinforced 3D printed calcium phosphate ceramic scaffold, characterized in that: The following steps are involved: S1. After fully mixing polyurethane acrylate, polyethylene glycol diacrylate and BYK-2155, add hydroxyapatite accounting for 60% of the total mass of the slurry and continue ball milling for 15 hours; then add whisker growth inducing component and continue ball milling for 2 hours; add TPO accounting for 1% of the mass of the organic phase and continue ball milling for 2 hours, and obtain 3D printing slurry after degassing; the whisker growth inducing component is strontium sulfate; the addition amount of the whisker growth inducing component is 10%-30% of the mass of hydroxyapatite; S2, adding 3D printing slurry into the printer, and at the same time importing the 3D model of the porous scaffold into the printer, and preparing the porous scaffold by using light-curing 3D printing technology; S3. Clean the porous scaffold with anhydrous ethanol and dry it naturally before degreasing and sintering. The heating curve is as follows: heat to 300 °C at 5 °C / min and keep it warm for 6 h; continue to heat to 600 °C at 5 °C / min and keep it warm for 2 h; then heat to 900 °C at 5 °C / min and keep it warm for 5-20 h; continue to heat to 1150 °C at 5 °C / min and keep it warm for 2 h. After the end, naturally cool to room temperature to obtain a mechanically reinforced 3D printed calcium phosphate ceramic scaffold.

2. The preparation method according to claim 1, characterized in that: The polyurethane acrylate, polyethylene glycol diacrylate and BYK-2155 are mixed in a mass ratio of 50:15:

1.

3. A mechanically reinforced 3D printed calcium phosphate ceramic scaffold prepared by the method according to claim 1 or 2.

4. Use of the mechanically reinforced 3D printed calcium phosphate ceramic scaffold as described in claim 3 in the preparation of bone defect repair materials.

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