Endogenous whisker reinforced porous calcium phosphate ceramic as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biomedical materials, and discloses endogenous whisker reinforced porous calcium phosphate ceramic as well as a preparation method and application thereof. The preparation method comprises the following steps: firstly, preparing porous calcium phosphate ceramic, and then immersing the ceramic in an organic solution for treatment to obtain the porous calcium phosphate ceramic with the surface encapsulated with the coating. And further, treating the porous calcium phosphate ceramic to expose reaction sites, putting the porous calcium phosphate ceramic into a hydrothermal reaction kettle of an aqueous solution medium, carrying out hydrothermal treatment, then carrying out heat treatment on the obtained ceramic, and finally obtaining the porous calcium phosphate ceramic with the endogenous whiskers. The porous calcium phosphate ceramic prepared by the invention not only has higher mechanical strength, but also has good bone repair performance, and has very important significance in promoting 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 an endogenous whisker-reinforced porous calcium phosphate ceramic and a preparation method and application thereof. Background Art

[0002] Porous calcium phosphate bioceramics, whose composition is close to the inorganic composition of human bone tissue, have good biocompatibility, osteoconduction, osteoinduction and osteogenic properties, etc., and are widely used in the field of biomedical materials, especially in bone defect repair and bone replacement materials. Good repair effects have been achieved. However, although calcium phosphate ceramics have excellent biological properties, their mechanical strength is insufficient due to their high porosity. At the same time, the inherent brittleness of the ceramics makes it difficult to apply them to load-bearing parts. Therefore, how to improve the mechanical properties of porous calcium phosphate ceramics is extremely important for their clinical application.

[0003] In order to improve the mechanical properties of porous calcium phosphate ceramics, fiber reinforcement, particle reinforcement and composite material design are often used. For example, Chinese patent CN113880568A discloses a method of enhancing calcium phosphate composite ceramics by in-situ doping with graphene; Chinese patent CN116606130A discloses a method of improving the mechanical strength of porous calcium phosphate ceramics by adding metal salts such as calcium sulfate and sintering to form a mechanically reinforced whisker structure. These methods usually need to be mixed into the matrix before the ceramic is sintered, which leads to poor interface bonding between the reinforcement and the matrix, thereby affecting the mechanical properties of the overall material; on the other hand, the chemical composition of calcium phosphate ceramics is changed, which may bring certain safety risks to later bone implant repair. Therefore, in order to achieve the purpose of not changing the chemical composition of calcium phosphate ceramics and improving the mechanical strength of porous calcium phosphate ceramics at the same time. Chinese patent CN103585677B discloses a method of adding hydroxyapatite whiskers to calcium phosphate ceramics to enhance the mechanical strength of the material. Chinese invention patent CN105343935A discloses a calcium phosphate whisker skeleton, which is compounded with ceramic slurry to obtain porous calcium phosphate ceramics with mechanical enhancement. Although the mechanical enhancement effect can be achieved, the mechanical enhancement effect on the ceramic is limited due to the disorder of the ceramic whisker structure and the weak bonding between the existing whiskers and the ceramic.

[0004] For porous calcium phosphate ceramics, how to improve their mechanical strength and biological activity without changing the chemical composition of the material, so as 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 solve the problem of insufficient mechanical strength and biological activity of calcium phosphate ceramics in the prior art by a method of constructing a whisker reinforcement structure inside the pore wall of porous calcium phosphate ceramics.

[0006] The technical solution adopted by the present invention is as follows: A porous calcium phosphate ceramic reinforced with endogenous whiskers has a whisker reinforcement structure constructed inside the pore wall of the porous calcium phosphate ceramic; the whiskers are composed of a single phase or two phases of hydroxyapatite or beta-tricalcium phosphate; the whisker reinforcement structure is distributed inside the pore wall, and the growth direction has a certain orientation.

[0007] Furthermore, the porous calcium phosphate ceramic has a porosity of 30% to 90% and a macropore size of 200 μm to 1000 μm.

[0008] The present invention provides a method for preparing the above-mentioned porous calcium phosphate ceramic reinforced with endogenous whiskers, comprising the following steps: Step 1. Prepare a calcium phosphate ceramic slurry, and then prepare a porous calcium phosphate ceramic through molding, degreasing and sintering steps; Step 2. preparing an organic solution, placing the porous calcium phosphate ceramic prepared in step 1 in the organic solution, and then vacuumizing to infuse the organic solution into the pores of the porous calcium phosphate ceramic, and drying to obtain a porous ceramic with a surface encapsulation coating; Step 3. Treat the porous ceramic with the surface encapsulation coating to expose the reaction sites, then perform hydrothermal treatment, take out and dry after the reaction is completed, and place it in a muffle furnace for heat treatment to finally obtain the porous calcium phosphate ceramic reinforced with endogenous whiskers.

[0009] Furthermore, the solid content of the ceramic slurry is 15% to 85%; the ceramic slurry is made of water, ceramic powder, dispersant, binder, photosensitive resin, two or more materials of PLA or PCL as raw materials, and is mixed by mechanical stirring or ball milling; the composition of the ceramic powder is a single phase or two-phase composition of hydroxyapatite or β-tricalcium phosphate.

[0010] Furthermore, the molding method in step 1 refers to an organic foam impregnation method, a pore-forming agent method green body, a hydrogen peroxide foaming method, or an additive manufacturing method; the degreasing and sintering refers to transferring the ceramic green body to a muffle furnace, degreasing in an air atmosphere, the degreasing temperature is 200~600℃, the insulation time is 1h~5h, and finally cooling with the furnace to obtain a porous calcium phosphate ceramic.

[0011] Furthermore, in step 2: the organic solution component is composed of one or more of graphene oxide, polyvinyl alcohol, polydopamine or chitosan, and the pH of the solution is 1-10; the drying method is air drying, oven drying or freeze drying.

[0012] Furthermore, the hydrothermal treatment described in step 3 refers to the pH of the aqueous solution medium being 2-9, the hydrothermal temperature being 100-250°C, and the treatment time being preferably 1-24h; the heat treatment after the hydrothermal treatment is performed at a temperature of 500-1000°C and a time of 1h-4h.

[0013] The present invention also provides application of the above-mentioned porous calcium phosphate ceramics reinforced with endogenous whiskers in bone defect regeneration and repair materials.

[0014] Compared with the prior art, the present invention has the following beneficial effects: The invention has a scientific design and a simple method. Without changing the chemical composition of the porous calcium phosphate ceramic, a whisker reinforcement structure with certain oriented growth is constructed inside the pore wall of the porous calcium phosphate ceramic, which not only retains the good biological properties of the material, but also helps to improve the mechanical strength of the porous calcium phosphate ceramic. This has a good promoting effect on the application of calcium phosphate ceramics in bone repair and has great social and economic value. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 is a morphology diagram of the porous calcium phosphate ceramic prepared in Example 1 of the present invention; Figure 1 (A) is the SEM morphology of the pore wall cross section of porous calcium phosphate ceramics; Figure 1 (B) SEM microstructure of the whisker structure inside the pore wall.

[0016] Figure 2 It is the compressive strength of the ceramic tested in Example 2 of the present invention. DETAILED DESCRIPTION

[0017] 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

[0018] (1) Using biphasic calcium phosphate ceramic powder (mass ratio of hydroxyapatite: β-tricalcium phosphate = 4:6) and acrylic photosensitive resin as raw materials, 3D printing ink with a solid content of 50% was obtained by ball milling for 4 hours. Then, a porous biphasic calcium phosphate ceramic body was printed using a DLP 3D printing mechanism. The body was further transferred to a muffle furnace and heated from room temperature to 600°C at a heating rate of 2°C / min, and kept warm for 2 hours. After the insulation was completed, the temperature was further increased to 1100°C, and kept warm for 2 hours. Finally, the porous calcium phosphate initial ceramic was obtained by cooling with the furnace. (2) Prepare an organic solution, prepare a graphene oxide solution by ultrasonic treatment, the solution concentration is 0.3 mg / mL, then place the porous calcium phosphate ceramic in the graphene oxide solution, and use vacuum infusion to allow the graphene oxide solution to enter the pores of the porous ceramic. Then take out the ceramic and transfer it to a 60°C oven for drying to obtain a porous calcium phosphate ceramic with a surface encapsulated graphene oxide coating; (3) The porous ceramic with the surface encapsulation coating is treated to expose the reaction site and transferred to a stainless steel reactor. The reaction solution medium is an aqueous solution with a pH of about 4, and then a hydrothermal treatment is performed at a temperature of 120°C for 6 hours. After the reaction is completed, the ceramic is taken out and placed in a 60°C oven for drying, and then placed in a muffle furnace and heated to 800°C at a heating rate of 5°C / min, kept warm for 2 hours, and finally cooled with the furnace to obtain a porous calcium phosphate ceramic with endogenous whiskers. The SEM morphology of the pore wall section of the porous calcium phosphate ceramic prepared in this embodiment is shown in the attached figure. Figure 1 As shown in (A), the pore wall consists of two layers, the outer layer is a grain structure and the inner layer is a whisker structure. The SEM microstructure of the whisker structure inside the pore wall is shown in the attached figure. Figure 1 As shown in (B), a large number of long whisker interlaced structures can be observed, showing obvious directional growth characteristics. Example 2

[0019] (1) β-tricalcium phosphate powder and acrylic photosensitive resin were used as raw materials to obtain 3D printing ink by ball milling for 6 hours, with a solid content of 40%. Then, a porous tricalcium phosphate ceramic body was printed by DLP 3D printing mechanism. The body was further transferred to a muffle furnace and heated from room temperature to 200°C at a heating rate of 2°C / min, and kept at this temperature for 1 hour. Then, the temperature was continued to be increased to 600°C at a heating rate of 2°C / min, and kept at this temperature for 2 hours. Then, the temperature was continued to be increased to 1050°C, and kept at this temperature for 2 hours. Finally, the porous calcium phosphate initial ceramic was obtained by cooling with the furnace. (2) Prepare an organic solution, prepare a graphene oxide solution by ultrasonic treatment, the solution concentration is 0.2 mg / mL, then place the porous calcium phosphate ceramic in the graphene oxide solution, and allow the graphene oxide solution to enter the pores of the porous ceramic by vacuum infusion. Then take out the ceramic and transfer it to a 60°C oven for drying to obtain a porous calcium phosphate ceramic with a surface encapsulated graphene oxide coating; (3) The porous ceramic with surface encapsulation coating is treated to expose the reaction site and transferred to a stainless steel reactor. The reaction solution medium is an aqueous solution with a pH of about 5, and then hydrothermally treated at a temperature of 150°C for 6 hours. After the reaction is completed, it is taken out and placed in a 60°C oven for drying, and then placed in a muffle furnace and heated to 600°C at a heating rate of 3°C / min, kept warm for 2 hours, and finally cooled with the furnace to obtain a porous calcium phosphate ceramic with endogenous whiskers. The mechanical strength of the ceramic prepared in this embodiment is as follows: Figure 2 As shown, the compressive strength of the ceramics tested by a universal testing machine is 2.43±0.20 MPa for the initial ceramics in this embodiment. Compared with the initial ceramics, the compressive strength of the endogenous whisker ceramics is significantly enhanced to 4.50±0.26 MPa. Example 3

[0020] (1) Using porous biphasic calcium phosphate ceramic powder (mass ratio of hydroxyapatite: β-tricalcium phosphate = 2:8) and acrylic photosensitive resin as raw materials, a 3D printing ink with a solid content of 55% was obtained by mechanical stirring for 30 minutes. Then, a porous biphasic calcium phosphate ceramic green body was printed using a DLP 3D printing mechanism. The green body was further transferred to a muffle furnace and heated from room temperature to 600°C at a heating rate of 1°C / min and kept warm for 4 hours; then the temperature was continued to be raised to 1150°C and kept warm for 2 hours. Finally, the porous calcium phosphate initial ceramic was obtained by cooling with the furnace. (2) Prepare an organic solution, prepare a polydopamine solution by ultrasonic treatment, the solution concentration is 0.2 mg / mL, then place the porous calcium phosphate ceramic in the graphene solution, and allow the graphene solution to enter the pores of the porous ceramic by vacuum infusion. Then take out the ceramic and transfer it to a 60°C oven for drying to obtain a porous calcium phosphate ceramic with a polydopamine coating encapsulated on the surface; (3) The porous ceramics with surface encapsulation coating were treated to expose the reaction sites and transferred to a stainless steel reactor. The reaction solution medium was an aqueous solution with a pH of about 5, and then hydrothermally treated at a temperature of 150°C for 8 hours. After the reaction was completed, the ceramics were taken out and placed in a 60°C oven for drying, and then placed in a muffle furnace and heated to 700°C at a heating rate of 3°C / min, kept warm for 2 hours, and finally cooled with the furnace to obtain porous calcium phosphate ceramics with endogenous whiskers. That is, the pore wall of the ceramic is composed of an internal whisker structure and an outer layer of grains, and the whiskers are long strips of staggered whiskers, showing a directional growth characteristic. Example 4

[0021] Compared with Example 1, the ceramic original powder in the configured slurry in this embodiment is biphasic calcium phosphate powder (mass ratio of hydroxyapatite: β-tricalcium phosphate = 3:7), the solid content of the slurry is 60wt.%, the 3D printing method is SLA light-curing 3D printing, and the organic solution is a graphene oxide / dopamine mixed solution. The conditions are the same, and a porous calcium phosphate ceramic with a whisker structure inside the pore wall and a grain structure outside is prepared.

Claims

1. A porous calcium phosphate ceramic reinforced with endogenous whiskers, characterized in that: A whisker reinforcement structure is constructed inside the pore wall of the porous calcium phosphate ceramic; the whisker is composed of a single phase or two phases of hydroxyapatite or beta-tricalcium phosphate; the whisker reinforcement structure is distributed inside the pore wall, and the growth direction has a certain orientation.

2. The porous calcium phosphate ceramic reinforced with endogenous whiskers according to claim 1, characterized in that: The porous calcium phosphate ceramic has a porosity of 30% to 90% and a macropore size of 200 μm to 1000 μm.

3. The method for preparing a porous calcium phosphate ceramic reinforced with endogenous whiskers according to claim 2, characterized in that: The following steps are involved: Step 1. Prepare a calcium phosphate ceramic slurry, and then prepare a porous calcium phosphate ceramic through molding, degreasing and sintering steps; Step 2. preparing an organic solution, placing the porous calcium phosphate ceramic prepared in step 1 in the organic solution, and then vacuumizing to infuse the organic solution into the pores of the porous calcium phosphate ceramic, and drying to obtain a porous ceramic with a surface encapsulation coating; Step 3. Treat the porous ceramic with the surface encapsulation coating to expose the reaction sites, then perform hydrothermal treatment, take out and dry after the reaction is completed, and place it in a muffle furnace for heat treatment to finally obtain the porous calcium phosphate ceramic reinforced with endogenous whiskers.

4. The method for preparing a porous calcium phosphate ceramic reinforced with endogenous whiskers according to claim 3, characterized in that: The solid content of the ceramic slurry is 15% to 85%; the ceramic slurry is made of water, ceramic powder, dispersant, binder, photosensitive resin, two or more materials of PLA or PCL as raw materials, and is mixed by mechanical stirring or ball milling; the composition of the ceramic powder is a single phase or two-phase composition of hydroxyapatite or β-tricalcium phosphate.

5. The method for preparing a porous calcium phosphate ceramic reinforced with endogenous whiskers according to claim 3, characterized in that: The molding method in step 1 refers to an organic foam impregnation method, a pore-forming agent method body, a hydrogen peroxide foaming method, or an additive manufacturing method; the degreasing and sintering refers to transferring the ceramic body to a muffle furnace, degreasing in an air atmosphere, the degreasing temperature is 200~600℃, the insulation time is 1h~5h, and finally cooling with the furnace to obtain a porous calcium phosphate ceramic.

6. The method for preparing a porous calcium phosphate ceramic reinforced with endogenous whiskers according to claim 3, characterized in that: In the step 2, the organic solution component is one or more of graphene oxide, polyvinyl alcohol, polydopamine or chitosan, and the pH of the solution is 1-10; the drying method is air drying, oven drying or freeze drying.

7. The method for preparing a porous calcium phosphate ceramic reinforced with endogenous whiskers according to claim 3, characterized in that: The hydrothermal treatment described in step 3 refers to the pH of the aqueous solution medium being 2-9, the hydrothermal temperature being 100-250°C, and the treatment time being preferably 1-24h; the heat treatment after the hydrothermal treatment is performed at a temperature of 500-1000°C and a time of 1h-4h.

8. Use of the endogenous whisker reinforced porous calcium phosphate ceramic according to claim 1 or 2 in bone defect regeneration and repair materials.

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