Preparation method and application of porous calcium phosphate ceramic with controllable communicating holes

Abstract

The invention belongs to the technical field of biomedical materials, and discloses a preparation method and application of porous calcium phosphate ceramic with controllable communicating holes. Filling a mold with a pore-forming agent, then pouring the ceramic slurry into pores of the pore-forming agent, and carrying out drying treatment to obtain a ceramic green body; and further, treating the ceramic body by using an isostatic pressing technology, and finally, degreasing and sintering to obtain the porous calcium phosphate ceramic. The porous calcium phosphate ceramic prepared by the invention not only has good connectivity, but also has good bone repair performance, and has very important significance for promoting the clinical application of the porous calcium phosphate ceramic.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, and in particular to a preparation method and application of porous calcium phosphate ceramics with controllable interconnected pores. Background Art

[0002] Maxillofacial bone tissue defects caused by trauma, congenital malformations, infections, tumors, etc. often cause serious facial deformities and functional disorders, so the defect site needs to be treated. Calcium phosphate bioceramics, whose composition is close to the inorganic composition of human bone tissue, have good biocompatibility, osteoconduction, osteoinduction and osteogenic properties, and are widely used in the repair of bone defects. In order to achieve good bone repair effects, calcium phosphate ceramics are usually prepared into porous structures, which can facilitate tissue growth and the transmission of nutrients after implantation into the defect site. However, for porous calcium phosphate ceramics, their permeability is crucial to the repair of bone defects, so how to further improve the permeability of porous ceramics is of great significance.

[0003] The pore-forming agent method is a common method for preparing porous calcium phosphate ceramics. For example, Chinese patent CN101721740A discloses a method for preparing porous calcium phosphate ceramics using paraffin microspheres as pore-forming agents, and the permeability of porous ceramics is regulated by adding paraffin microspheres of different particle sizes. However, although the permeability is regulated by controlling the particle size distribution and the amount of addition of the microspheres, the size of the connected pores cannot be effectively regulated. Chinese patent CN110078493A discloses a method for preparing ceramic microspheres by a template method, in which organic microspheres are added to a mold, and an organic framework is made by physical heating, pressurization or chemical dissolution, and then the ceramic slurry is poured into the framework, and porous ceramics are prepared by degreasing and sintering. However, chemical dissolution of microspheres may produce chemical residues, affecting the biosafety of ceramics; direct physical heating and / or pressurization of the organic framework has temperature or stress gradients, and the size of the connected pores of porous ceramics cannot be accurately regulated. In order to control the connectivity of calcium phosphate ceramics, PMMA microspheres are used as pore-forming agents, and the surfaces of the accumulated PMMA microspheres are dissolved and connected by chemical methods, and porous calcium phosphate ceramics are prepared using this as a template (Journal of the European Ceramic Society, 2008, 28 (1): 149-157). However, this method has a complicated preparation process, and it is difficult to accurately control the size of the connected pores of porous ceramics by chemically dissolving PMMA microspheres.

[0004] For porous calcium phosphate ceramics, permeability is the key to affecting tissue ingrowth and nutrient transport. How to accurately control the permeability of porous calcium phosphate ceramics to meet the clinical requirements for bone defect regeneration and repair materials is a technical problem that calcium phosphate ceramics urgently need to solve. Summary of the invention

[0005] The technical problem solved by the present invention is to provide a method for accurately controlling the size of the interconnected pores of porous calcium phosphate ceramics by isostatic pressing technology, thereby controlling the connectivity thereof, and solving the problem that the connectivity of calcium phosphate ceramics in the prior art is difficult to accurately control.

[0006] The technical solution adopted by the present invention is as follows: A method for preparing a porous calcium phosphate ceramic with controllable interconnected pores, wherein the porous calcium phosphate ceramic green body is treated by an isostatic pressing method, and the isostatic pressing treatment conditions of the green body are changed: different pressures, temperatures and times are applied, so as to achieve control of the interconnectedness of the porous calcium phosphate ceramic, wherein the interconnected pores are connected between the macropores of the porous calcium phosphate ceramic, and the size of the connected pores is 10-600 μm.

[0007] Further, the following steps are included: Step 1. The pore-forming agent is formed into a template with a certain shape and pore structure through a molding technology; Step 2. preparing a ceramic slurry, and pouring the slurry into the pores of the template formed by the pore-forming agent, and drying to obtain a ceramic body; Step 3. Place the dried green body into an isostatic press for processing; Step 4. Place the green body after isostatic pressing into a muffle furnace for degreasing and sintering to finally obtain the porous calcium phosphate ceramic.

[0008] Furthermore, the pore-forming agent is composed of one or more of polymethyl methacrylate, stearic acid, polycaprolactone, polylactic acid, paraffin, polyvinyl alcohol or polyacrylic resin; the molding method of the pore-forming agent to form a template is to fill the pore-forming agent particles into a hollow mold for stacking molding or to prepare the pore-forming agent into a porous structure by 3D printing.

[0009] Furthermore, the ceramic slurry has a solid content of 10% to 90%. The ceramic slurry is prepared by using water, ceramic powder, dispersant, and binder as raw materials and mixing them by mechanical stirring or ball milling.

[0010] Furthermore, the ceramic powder is composed of one or two of a single phase or multiple phases of hydroxyapatite or tricalcium phosphate.

[0011] Furthermore, the isostatic pressing method is to wrap the ceramic body in a flexible sheath, evacuate the sheath, and place it in an isostatic press; the isostatic pressing is one or a combination of cold isostatic pressing and hot isostatic pressing; the isostatic pressing treatment conditions are a treatment pressure of 10MPa~500MPa, a treatment temperature of 25~500℃, and a treatment time of 1min~6h.

[0012] Furthermore, the degreasing and sintering refers to: degreasing in a muffle furnace under an air atmosphere, the degreasing temperature is 80~600°C, and after degreasing, the temperature can be continued to be raised in the muffle furnace for sintering to obtain the porous calcium phosphate ceramic; or after degreasing, it is cooled to room temperature and then transferred to a vacuum sintering furnace or a microwave sintering furnace and raised to 700~1200°C for sintering; the sintering insulation time is 5min~6h.

[0013] Furthermore, the porosity of the porous calcium phosphate ceramic is 20% to 90%, the macropore morphology is preferably spherical pores, square pores or irregular pores, and the macropore size is 50 to 1500 μm.

[0014] The invention provides a porous calcium phosphate ceramic with controllable interconnected pores, which is prepared by the above method.

[0015] The present invention also provides an application of porous calcium phosphate ceramics with controllable interconnected pores in bone defect regeneration and repair materials.

[0016] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention is scientifically designed and simple in method. The porous ceramic body is treated by isostatic pressing, and the size of the interconnected pores of the porous ceramic is adjusted by changing the isostatic pressing treatment conditions. The material has good permeability, which is beneficial to the transmission of nutrients and has a certain promoting effect on the bone repair performance of the material.

[0017] (2) The method of the present invention uses physical methods instead of chemical reagent dissolution to control the interconnected pores, thus avoiding the residue of chemical reagents, having good biosafety and simple operation. Finally, the green body subjected to isostatic pressing is subjected to uniform force, and the final density of the ceramic is higher, which is beneficial to improving the mechanical strength of porous calcium phosphate ceramics.

[0018] (3) The preparation method of the present invention has good permeability and mechanical strength, which is conducive to improving its bone repair performance and meeting the requirements for material performance in clinical medicine. It has a good promoting effect on the clinical application of calcium phosphate ceramics and generates great social and economic value. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a morphology picture of the porous calcium phosphate ceramic with controllable interconnected pores prepared in Example 1 of the present invention; Figure 1 (A) is the low magnification SEM morphology of ceramics. Figure 1 (B) High-magnification SEM microstructure of the ceramic.

[0020] Figure 2 This is a morphology picture of the porous calcium phosphate ceramic with controllable interconnected pores prepared in Example 2 of the present invention; Figure 2 (A) is the low magnification SEM morphology of ceramics. Figure 2(B) High-magnification SEM microstructure of the ceramic. DETAILED DESCRIPTION

[0021] The above contents of the present invention are further described in detail below by means of specific implementation methods in the form of examples, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. Example 1

[0022] (1) Stearic acid is used as a pore-forming agent, and the particle size is screened to be 800-1000 μm. The pore-forming agent is then filled into a hollow mold and vibrated evenly; (2) Weigh 60g of hydroxyapatite powder, 40g of deionized polyvinyl alcohol solution (PVA: deionized water = 3:47), and 2g of dispersant, put all the raw materials into a ball mill, and ball mill for 2h to obtain a ceramic slurry. Then pour the prepared ceramic slurry into the gaps of the stearic acid template, and obtain a ceramic body by drying and demolding; (3) Wrap the ceramic body with a flexible sleeve and evacuate and seal it. Place the sleeve in a cold isostatic press and then seal the entire system. Set the parameters of the cold isostatic press to a time of 10 minutes and a pressure of 100 MPa. After the time is up, release the pressure and take out the material to obtain the ceramic body. (4) Place the ceramic body in a muffle furnace. In an air atmosphere, heat the furnace from room temperature to 150°C at a heating rate of 1°C / min and keep it at that temperature for 1 hour. Then heat it to 500°C at a heating rate of 1°C / min and keep it at that temperature for 2 hours. Further, heat it to 1150°C at a heating rate of 3°C / min and keep it at that temperature for 2 hours. Finally, cool it down with the furnace to obtain porous calcium phosphate ceramics. The low-magnification SEM morphology of the ceramic prepared in this embodiment is shown in the attached figure. Figure 1 As shown in (A), it can be observed that the prepared porous ceramics have good connectivity, and the average size of the interconnected pores between the macropores is about 245 μm; the high-magnification SEM micromorphology of the ceramics is shown in the attached Figure 1 As shown in (B), due to the higher molding pressure of isostatic pressing, the grains of porous ceramics are denser and have fewer micropores. Example 2

[0023] (1) Stearic acid is used as a pore-forming agent, and the particle size is screened to be 300-600 μm. The pore-forming agent is then filled into a hollow mold and vibrated evenly; (2) Weigh 50g of porous biphasic calcium phosphate ceramic powder (mass ratio HA: β-TCP = 3:7), 50g of deionized polyvinyl alcohol solution (PVA: deionized water = 3:47), and 1.5g of dispersant, put all the raw materials into a beaker, and stir mechanically for 30 minutes to prepare a ceramic slurry. Then pour the prepared ceramic slurry into the gaps of the stearic acid template, and prepare a ceramic body by drying and demolding; (3) Wrap the ceramic body with a flexible sleeve and evacuate and seal it. Place the sleeve in a cold isostatic press and then seal the entire system. Set the parameters of the cold isostatic press to 5 minutes and a pressure of 50 MPa. After the time is up, release the pressure and take out the material to obtain the ceramic body. (4) Place the ceramic body in a muffle furnace. In an air atmosphere, heat the furnace from room temperature to 200°C at a heating rate of 0.5°C / min and keep it at that temperature for 2 hours. Then heat it to 600°C at a heating rate of 1°C / min and keep it at that temperature for 2 hours. Further, heat it to 1100°C at a heating rate of 5°C / min and keep it at that temperature for 2 hours. Finally, cool it down with the furnace to obtain porous calcium phosphate ceramics. The low-magnification SEM morphology of the ceramic prepared in this embodiment is shown in the attached figure. Figure 2 As shown in (A), it can be observed that the porous ceramics prepared under this condition have good connectivity, with smaller interconnected pores between the macropores, and the average size of the interconnected pores is about 91 μm; the high-magnification SEM microstructure of the ceramics is shown in the attached Figure 2 (B) As shown, there are abundant micropore structures between the grains of porous ceramics. Example 3

[0024] (1) Use paraffin microspheres as pore-forming agent with a particle size of about 500-600 μm, then fill the pore-forming agent into a hollow mold and vibrate it evenly; (2) Weigh 35g of β-tricalcium phosphate powder, 65g of deionized polyvinyl alcohol solution (PVA: deionized water = 3:47), and 1g of dispersant, put all the raw materials into a ball mill, and ball mill for 2h to obtain a ceramic slurry. Then pour the prepared ceramic slurry into the voids of the paraffin microsphere template, and obtain a ceramic body by drying and demolding; (3) Wrap the ceramic body with a bag and evacuate and seal it. Place the bag in a cold isostatic press and seal it. Set the parameters of the isostatic press to 10 minutes and a pressure of 200 MPa. After the time is up, release the pressure and take out the material to obtain the ceramic body. (4) The ceramic body is placed in a muffle furnace. In an air atmosphere, the furnace is heated from room temperature to 100°C at a heating rate of 1°C / min and kept at this temperature for 1 hour. Then, the temperature is raised to 200°C at a heating rate of 1°C / min and kept at this temperature for 2 hours. Then, the temperature is raised to 600°C at a heating rate of 2°C / min and kept at this temperature for 2 hours. Further, the temperature is raised to 1050°C at a heating rate of 5°C / min and kept at this temperature for 2 hours. After the procedure is completed, the temperature is lowered along with the furnace, and finally a porous calcium phosphate ceramic with a composition of tricalcium phosphate, good permeability, a connected pore size of about 110 μm, and a relatively dense pore wall is obtained. Example 4

[0025] Compared with Example 2, the ceramic original powder in the configured slurry in this embodiment is biphasic calcium phosphate powder (hydroxyapatite: β-tricalcium phosphate = 4:6), the solid content of the slurry is 55wt.%, the pore-forming agent is PMMA, and the conditions are the same. The prepared porous calcium phosphate ceramic has good permeability and a relatively large number of microporous structures.

Claims

1. A method for preparing a porous calcium phosphate ceramic with controllable interconnected pores, characterized in that: The porous calcium phosphate ceramic body is treated by isostatic pressing. By changing the isostatic pressing conditions of the body: applying different pressures, temperatures and times, the connectivity of the porous calcium phosphate ceramic can be regulated. The connectivity refers to the presence of connected pores between the macropores of the porous calcium phosphate ceramic, and the size of the connected pores is 10-600 μm.

2. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 1, characterized in that: The following steps are involved: Step 1. The pore-forming agent is formed into a template with a certain shape and pore structure through a molding technology; Step 2. preparing a ceramic slurry, and pouring the slurry into the pores of the template formed by the pore-forming agent, and drying to obtain a ceramic body; Step 3. Place the dried green body into an isostatic press for processing; Step 4. Place the green body after isostatic pressing into a muffle furnace for degreasing and sintering to finally obtain the porous calcium phosphate ceramic.

3. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 2, characterized in that: The pore-forming agent is composed of one or more of polymethyl methacrylate, stearic acid, polycaprolactone, polylactic acid, paraffin, polyvinyl alcohol or polyacrylic resin; the molding method of the pore-forming agent to form a template is to fill the pore-forming agent particles into a hollow mold for stacking molding or to prepare the pore-forming agent into a porous structure by 3D printing.

4. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 3, characterized in that: The solid content of the ceramic slurry is 10% to 90%. The preparation method of the ceramic slurry is to use water, ceramic powder, dispersant and binder as raw materials and mix them by mechanical stirring or ball milling.

5. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 4, characterized in that: The ceramic powder is composed of one or two phases of hydroxyapatite or tricalcium phosphate.

6. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 5, characterized in that: The isostatic pressing method comprises the following steps: wrapping the ceramic body in a flexible package, evacuating the package, and placing the package in an isostatic press; the isostatic pressing is one of cold isostatic pressing and hot isostatic pressing, or a combination of the two; the isostatic pressing treatment conditions are a treatment pressure of 10MPa to 500MPa, a treatment temperature of 25 to 500°C, and a treatment time of 1min to 6h.

7. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 2, characterized in that: The degreasing and sintering refers to: degreasing in a muffle furnace under air atmosphere, the degreasing temperature is 80~600℃, and after degreasing, the temperature can be continued to be raised in the muffle furnace for sintering to obtain the porous calcium phosphate ceramic; or after degreasing, it is cooled to room temperature and then transferred to a vacuum sintering furnace or a microwave sintering furnace and raised to 700~1200℃ for sintering; the sintering insulation time is 5min~6h.

8. The method for preparing a porous calcium phosphate ceramic with controllable interconnected pores according to claim 7, characterized in that: The porous calcium phosphate ceramic has a porosity of 40% to 90%, a macropore morphology of spherical pores, square pores or irregular pores, and a macropore size of 100 to 1000 μm.

9. A porous calcium phosphate ceramic with controllable interconnected pores, characterized in that: Prepared according to any one of claims 1 to 8.

10. Use of the porous calcium phosphate ceramic with controllable interconnected pores according to claim 9 in bone defect regeneration and repair materials.

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