Calcium phosphate bone implant material with high stacking porosity and preparation method thereof

Abstract

The invention discloses a calcium phosphate bone implant material with high stacking porosity and a preparation method thereof, and relates to the field of biomedical new materials, the material comprises the following components by mass: 0.4-0.6 part of a self-curing slurry, and 0.6 part of steel balls; the mass ratio of the self-curing slurry to the steel balls is (1: 1)-(1: 1.5); the diameter of the steel ball is 0.5 to 1.5 mm; the self-curing slurry is bionic calcium phosphorus slurry; the invention accidentally finds that the bionic calcium-phosphorus artificial bone particles prepared from the bionic calcium-phosphorus slurry and the 1mm steel balls have a synergistic effect on improving the pore distribution of the particles; by improving the pore-forming formula and the preparation method of the artificial bone repair material, the porosity and pore size distribution of the granular artificial bone are remarkably improved, and the defects that a traditional artificial bone material needs additional additives and is sintered at high temperature are overcome.

Description

Technical Field

[0001] This invention relates to the field of new biomedical materials, and in particular to a calcium phosphate bone implant material with high packing porosity and its preparation method. Background Technology

[0002] Bone defect repair and regeneration have always been a research hotspot in clinical medicine and biomaterials. Calcium phosphate (CaP)-based artificial bone (such as hydroxyapatite and β-tricalcium phosphate) is widely used as a scaffold and filler material in bone tissue engineering due to its similar chemical composition to human bone tissue, excellent biocompatibility, osteoconductivity, and biodegradability. In the bone repair process, the pore structure of the implant material is crucial. Ideal bone implant materials should have a highly interconnected pore network: macropores (>100µm) facilitate osteoblast migration, infiltration, and angiogenesis; micropores (<10µm) aid in nutrient transport, protein adsorption, and enhance the material's bioactivity.

[0003] Currently, in order to introduce pores into artificial bone implant materials, researchers at home and abroad have developed a variety of pore-forming methods, mainly including the following: (1) Sacrificial Template Method: This method involves adding organic pore-forming agents (such as paraffin, naphthalene, polymer microspheres, salt particles, etc.) to calcium phosphate slurry, and after molding and drying, removing the organic matter by heating or solvent extraction, thereby leaving pores. (2) Foaming Method: This method involves introducing gas into the slurry (generated by physical stirring or chemical reaction), using surfactants to stabilize the bubbles, and then sintering to fix the pores. (3) 3D Printing Additive Manufacturing: Using computer-aided design (CAD) guidance, a scaffold with precise geometric pores is constructed by layer-by-layer accumulation. Most of the artificial bone implant materials prepared by the above three methods require toxic and harmful substances such as pore-forming agents and binders, and the final curing still requires high-temperature calcination. The market needs an artificial bone material that does not require additional additives and does not require high-temperature sintering. This invention solves this problem while significantly improving the porosity and pore size distribution of granular artificial bone. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a calcium phosphate bone implant material with high packing porosity and its preparation method. By improving the pore-forming formula and preparation method of artificial bone repair material, the porosity and pore size distribution of granular artificial bone are significantly improved, overcoming the defects of traditional artificial bone materials that require additional additives and high-temperature sintering.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A calcium phosphate bone implant material with high packing porosity comprises, by weight parts: 0.4-0.6 parts of self-curing slurry and 0.6 parts of steel balls; the diameter of the steel balls is 0.5-1.5 mm.

[0006] Furthermore, as an example, the self-curing slurry is a biomimetic calcium phosphate slurry. The biomimetic calcium phosphate slurry is obtained by adjusting the pH of a 1-5 times concentration supersaturated calcium phosphate solution to 5.5-6 using tromethorphan solution to form a milky white suspension, then continuing to add tromethorphan solution to bring the pH to 7.35-7.45, followed by a water bath shaking reaction, removal of the supernatant, washing, and solid-liquid separation.

[0007] In the aforementioned calcium phosphate bone implant material with high packing porosity, the supersaturated calcium phosphate solution at a 1:1 concentration is: Na + 140mM, Ca 2+ 4mM, Cl -1 84 mM and 2 mM phosphorus source; as one example, solutions with concentrations of 2, 3, 4, and 5 times are used, and so on.

[0008] The aforementioned calcium phosphate bone implant material with high packing porosity is washed by removing the supernatant after standing and resuspending. Specifically, after standing for more than 0.5 hours, 4 / 5 to 1 / 2 of the supernatant is removed, and an equal volume of deionized water is added. The mixture is stirred at 120 rpm for more than 10 minutes. The washing method and parameters are not limited, as long as it can achieve thorough cleaning.

[0009] The aforementioned calcium phosphate bone implant material with high packing porosity is separated into solid and liquid by centrifugation at a speed of 10,000 rpm or higher. The centrifugation method and parameters are not limited, and any method that can achieve solid-liquid separation is applicable to this invention.

[0010] The aforementioned calcium phosphate bone implant material with high packing porosity produces a biomimetic calcium phosphate slurry with a solid content of 70%.

[0011] Furthermore, as a preferred option, the diameter of the steel ball is 1 mm.

[0012] Furthermore, as one embodiment, the calcium phosphate bone implant material is a biomimetic calcium phosphate artificial bone particle, which is a 0.25-1mm particle made by grinding a self-curing slurry with steel balls.

[0013] The aforementioned calcium phosphate bone implant material with high packing porosity is obtained by combining 1 mm diameter steel balls with biomimetic calcium phosphate slurry at a mass ratio of 1:1.

[0014] A method for preparing a calcium phosphate bone implant material with high packing porosity includes the following steps: Step 1: Prepare the self-curing slurry. The self-curing slurry is a biomimetic calcium phosphate slurry. The specific preparation method of the biomimetic calcium phosphate slurry is as follows: The pH of a 1-5 times concentration supersaturated calcium-phosphorus solution was adjusted to 5.5-6 using tromethamine solution to form a milky white suspension. Tromethamine solution was then added to bring the pH to 7.35-7.45. After water bath shaking reaction, the supernatant was removed, and the mixture was washed and separated to obtain a biomimetic calcium-phosphorus slurry. The 1 times concentration supersaturated calcium-phosphorus solution included Na... + 130-150mM, Ca 2+ 3-5mM, Cl -1 The solution contains 80-88 mM calcium phosphate and 1-3 mM phosphorus source. The washing method involves resuspending the solution by standing for at least 0.5 hours, then removing 4 / 5 to 1 / 2 of the supernatant and adding an equal volume of deionized water. The solution is then stirred at 100-140 rpm for at least 10 minutes. Solid-liquid separation is achieved by centrifugation at a speed of at least 10,000 rpm. The prepared biomimetic calcium phosphate slurry has a solid content of 70%. Step two involves preparing the composite material of steel balls and self-curing slurry. Specific methods include: First, weigh the biomimetic calcium phosphate slurry prepared in step one; add steel balls with a diameter of 0.5-1.5 mm to the biomimetic calcium phosphate slurry, and control the mass ratio of the steel balls to the biomimetic calcium phosphate slurry to be 1:1-1.5:1 to obtain a composite block; Step 3 involves preparing biomimetic calcium-phosphate artificial bone particles of specific size and stacked pores. The specific steps include: first, extruding and mixing the composite block until the thickness of the mixed block is 0.5 to 1 cm; then drying, preferably using an air-drying process; placing the mixed block into a laminar flow drying space with an air velocity controlled at 0.3 m / s-0.6 m / s; separating the steel balls from the calcium phosphate solid; crushing the solidified calcium phosphate solid using a grinding device; initial sieving of the material using a sieve; and further confinement, separation, and shaping using a magnet or magnetic field to obtain biomimetic calcium-phosphate artificial bone particles, with a particle diameter preferably 0.25-1 mm.

[0015] The advantages of this invention are: The biomimetic calcium-phosphorus slurry and 1mm steel balls used in this invention have a synergistic effect in improving the porosity distribution of the particles. Compared with traditional grinding and cutting processes, it significantly changes the particle morphology and increases the porosity of bone repair materials; Compared to traditional pore-forming processes, no additional pore-forming agent is required; The process is simple and low-cost. The hole-making molds used in this method are reusable and suitable for large-scale production. This method is a physical shaping process that does not require the use of additional toxic or harmful reagents and has high biological safety. This method does not require high-temperature sintering or the addition of binders, resulting in low energy consumption and environmental friendliness.

[0016] Proper nouns: Self-setting putty is a type of material system that can transform from a fluid putty into a solid hardened body at room temperature through chemical reactions between its components without the need for external heating, light, or other special activating conditions. It is commonly used in the biomedical field (such as calcium phosphate bone cement products). Examples include biomimetic calcium phosphate putty, calcium sulfate, and polymethyl methacrylate (PMMA). This invention preferably uses biomimetic calcium phosphate putty, but other options are not limited; any technology belonging to the same inventive concept as this invention is within the scope of protection of this invention.

[0017] Calcium phosphate artificial bone: refers to artificial bone made of calcium phosphate granules formed by biomimetic calcium phosphate slurry and steel balls, and then shaped by the biomimetic calcium phosphate artificial bone slurry. The biomimetic calcium phosphate slurry can be hydroxyapatite, tricalcium phosphate, amorphous calcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, etc. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the results of Experiment 3 of the present invention; wherein, (A) is a macroscopic observation diagram of the particles obtained in the embodiment, (B) is a scanning electron microscope observation diagram of the particles obtained in the embodiment, (C) is a macroscopic observation diagram of the particles obtained in the comparative embodiment, and (D) is a scanning electron microscope observation diagram of the particles obtained in the comparative embodiment. Figure 2 These are the results of microCT scanning in Experiment 4 of this invention; among them, (A) representative images of the long axis and cross-section of MicroCT; (B) 3D reconstruction of the two particulate materials after stacking; (C) macroscopic porosity measured by MicroCT; (D) surface area / volume ratio of the two materials; Figure 3 Experiment 5 of this invention uses a mercury porosimeter to detect the porosity distribution. Detailed Implementation

[0019] The present invention will be described in detail below with reference to specific embodiments.

[0020] Example: Preparation of biomimetic calcium phosphate slurry. The specific preparation method of biomimetic calcium phosphate slurry is as follows: The pH of a 1:1 supersaturated calcium phosphate solution was adjusted to 5.5-6 using tromethamine solution until a milky white suspension was formed. Tromethamine solution was then added to bring the pH to 7.35-7.45. After a water bath shaking reaction, the supernatant was removed, and the mixture was washed and separated to obtain a biomimetic calcium phosphate slurry. The 1:1 supersaturated calcium phosphate solution included Na... + 140mM, Ca 2+ 4mM, Cl - 1 The supernatant was removed after standing and resuspending for more than 0.5 hours. 4 / 5 to 1 / 2 of the supernatant was removed, and an equal volume of deionized water was added. The mixture was stirred at 120 rpm for more than 10 minutes. Solid-liquid separation was performed by centrifugation at a speed of 10,000 rpm or higher. The prepared biomimetic calcium-phosphorus slurry had a solid content of 70%.

[0021] Experiment 1: Screening for suitable steel ball sizes: Bionic calcium phosphate slurry was mixed with steel balls of different sizes at a ratio of 1:1, dried, ground, and sieved to prepare bone filler particles of 0.25-1 mm. The particles were loaded into a tapped density meter, and the bulk density of the powder was measured using a powder tapped density meter. The results are shown in Table 1 below. Table 1 Steel ball size (mm) Volume per unit weight (ml / g) No steel balls used 1.29 0.5 1.55 0.7 1.58 1 1.62 1.5 1.43 1.8 1.21 2 1.26 Experiment 2: Ratio of self-curing slurry to steel balls: Bone filler particles of 0.25-1 mm were prepared by mixing biomimetic calcium phosphate slurry with 1 mm steel balls in different weight ratios, drying, grinding, and sieving. The particles were loaded into a tapped density meter, and the bulk density of the powder was measured. The difficulty of the operation was also assessed. The results are shown in Table 2 below. Table 2 Slurry: steel balls Volume per unit weight (ml / g) particle mixing degree Wet plasticity Mixed state 1:0.5 1.45 + ++ Uneven mixing of particles makes it difficult to shape into blocks. 1:1 1.66 +++ +++ Particles are mixed evenly 1:1.25 1.65 ++++ ++++ The particles are mixed relatively evenly, and the wet particles are compact after compounding. 1:1.5 1.68 +++++ ++++ The particles are mixed most evenly, and the wet particles are compact after compounding. 1:2 1.61 +++ ++ Granular and wet materials are relatively loose and prone to cracking. The results in Table 2 show that the slurry to steel ball mass ratio of 1:1 to 1:1.5 results in relatively uniform particle mixing.

[0022] Experiment 3, Visual Verification: Example: Following the preparation method of this invention, a preferred 1mm steel ball is composited with the above-obtained biomimetic calcium phosphate slurry in a 1:1 ratio to prepare biomimetic calcium phosphate artificial bone particles of specific size and stacked pores. Specific steps include: first, extruding and mixing the composite block until the thickness of the mixed block is approximately 0.5 to 1 cm; then drying, preferably using an air-drying process; placing the mixed block into a laminar flow drying space with an air velocity controlled at 0.3 m / s to 0.6 m / s; separating the steel ball from the artificial bone of suitable size; crushing the solidified calcium phosphate using a grinding device; initial sieving of the material using a sieve; and obtaining biomimetic calcium phosphate artificial bone particles after one-step constraint separation and shaping using a magnet or magnetic field, grinding them into particles with a size of 0.25-1 mm. The particles are then observed macroscopically and under a scanning electron microscope as shown below. Figure 1 A- Figure 1 B in the middle.

[0023] Comparative Example: The biomimetic calcium phosphate slurry prepared above was extruded and mixed evenly, and the thickness of the mixed block was approximately 0.5 to 1 cm; then it was dried using an air-drying process; the mixed block was placed in a laminar flow drying space, with the air velocity controlled at 0.3 m / s to 0.6 m / s; the solidified calcium phosphate was crushed using a grinding device; the material was initially sieved using a sieve to obtain biomimetic calcium phosphate artificial bone particles, which were then ground into particles with a particle size of 0.25-1 mm without the addition of steel balls. The particles were observed macroscopically and under a scanning electron microscope. Figure 1 C- Figure 1 As shown in D in the diagram.

[0024] Depend on Figure 1 It can be seen that the particles obtained in the example have high packing and good porosity.

[0025] Experiment 4: Verification of particle packing porosity in MicroCT: The particles prepared in the above examples (Test group) and the particles obtained without steel balls in the comparative example (Control group) were loaded into a 1ml syringe and subjected to microCT scanning to analyze the pore structure distribution of the two types of particles. The results are as follows: (A) Representative images of the long axis and cross-section of the microCT; (B) 3D reconstruction of the two particle materials after stacking; (C) Macroscopic porosity measured by microCT; (D) Surface area / volume ratio of the two materials, such as... Figure 2 As shown.

[0026] Experiment 5: Mercury intrusion porosimetry to test the pore distribution of two types of particles: The porosity distribution of the particles prepared in the above examples (test group, same sample measured three times) and the particles obtained without steel balls in the comparative example (control group, same sample measured three times) were analyzed using a mercury porosimeter. The pore structure distribution of the two types of particles was analyzed in detail. The results are as follows: Figure 3 As shown: (A) Porosity, pore surface area, and pore volume; (B) Pore distribution of the two types of particles; As can be seen from the figure: Although the porosity (73.8±0.51% vs 70.8±0.46%), pore surface area (approximately 127.2±4.9 m² / g vs 70.5±10.6 m² / g), and pore volume of the particles prepared in the example showed an increasing trend, they did not reach a statistically significant level (P = 0.0558). Pore size distribution analysis showed that both groups of particles exhibited a bimodal distribution in the nanopore (10–100 nm) and micropore (100,000–1,000,000 nm) scales, while the bimodal distribution of the particle curve prepared in the example shifted to both sides, indicating that the macropores formed by its particles were larger and the nanopores were smaller.

[0027] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the above embodiments do not limit the present invention in any way, and all technical solutions obtained by equivalent substitution or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A calcium phosphate bone implant material with high packing porosity, characterized in that, The composition by weight includes: 0.4-0.6 parts of self-curing slurry and 0.6 parts of steel balls; the diameter of the steel balls is 0.5-1.5 mm; the self-curing slurry is a biomimetic calcium-phosphorus slurry, which is obtained by adjusting the pH of a 1-5 times concentration supersaturated calcium-phosphorus solution to 5.5-6 using tromethamine solution to form a milky white suspension, then continuing to add tromethamine solution to bring the pH to 7.35-7.45, followed by a water bath shaking reaction, removal of the supernatant, washing, and solid-liquid separation.

2. The calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, in, A supersaturated calcium-phosphorus solution with a concentration of 1: Na + 140mM, Ca 2+ 4mM, Cl -1 84mM and phosphorus source 2mM.

3. The calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, The washing method involves removing the supernatant after standing and resuspending. Specifically, after standing for more than 0.5 hours, remove 4 / 5 to 1 / 2 of the supernatant and add an equal volume of deionized water. Stir at 120 rpm for more than 10 minutes.

4. The calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, The solid-liquid separation method is centrifugation, and the centrifugation rate is above 10,000 rpm.

5. The calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, The prepared biomimetic calcium phosphate slurry has a solid content of 70%.

6. The calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, The diameter of the steel ball is 1 mm.

7. The calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, The calcium phosphate bone implant material is a biomimetic calcium phosphate artificial bone particle, which is a 0.25-1mm particle made by grinding a self-curing slurry with steel balls.

8. A calcium phosphate bone implant material with high packing porosity according to claim 1, characterized in that, The calcium phosphate bone implant material is obtained by combining steel balls with a diameter of 1 mm and biomimetic calcium phosphate slurry at a mass ratio of 1:

1.

9. A method for preparing a calcium phosphate bone implant material with high packing porosity, characterized in that, Includes the following steps: Step 1: Prepare a self-curing slurry, which is a biomimetic calcium phosphate slurry. The specific preparation method is as follows: The pH of a 1-5 times concentration supersaturated calcium phosphate solution was adjusted to 5.5-6 using tromethamine solution until a milky white suspension was formed. Tromethamine solution was then added to bring the pH to 7.35-7.

45. After a water bath shaking reaction, the supernatant was removed, and the mixture was washed and separated to obtain a biomimetic calcium phosphate slurry. The 1 times concentration supersaturated calcium phosphate solution contained Na... + 130-150mM, Ca 2+ 3-5mM, Cl -1 The mixture contains 80-88 mM calcium phosphate and 1-3 mM phosphorus source. The washing method involves resuspending the mixture and removing the supernatant. The method is as follows: after standing for at least 0.5 hours, remove 4 / 5 to 1 / 2 of the supernatant and add an equal volume of deionized water. Stir at 100-140 rpm for at least 10 minutes. The solid-liquid separation method is centrifugation at a speed of at least 10,000 rpm. The prepared biomimetic calcium phosphate slurry has a solid content of 70%. Step two involves preparing the composite material of steel balls and self-curing slurry. Specific methods include: First, weigh the biomimetic calcium phosphate slurry prepared in step one; add steel balls with a diameter of 0.5-1.5 mm to the biomimetic calcium phosphate slurry, and control the mass ratio of the steel balls to the biomimetic calcium phosphate slurry to be 1:1-1.5:1 to obtain a composite block; Step 3 involves preparing biomimetic calcium-phosphate artificial bone particles of specific size and stacked pores. The specific steps include: first, extruding and mixing the composite block until the thickness of the mixed block is 0.5 to 1 cm; then drying, preferably using an air-drying process; placing the mixed block into a laminar flow drying space with an air velocity controlled at 0.3 m / s-0.6 m / s; separating the steel balls from the calcium phosphate solid; crushing the solidified calcium phosphate solid using a grinding device; initial sieving of the material using a sieve; and further confinement, separation, and shaping using a magnet or magnetic field to obtain biomimetic calcium-phosphate artificial bone particles, with a particle diameter preferably 0.25-1 mm.

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