CN113248278B - Modified zirconia ceramic with surface compounded with bioactive substances and preparation method thereof - Google Patents

Abstract

The invention discloses a modified zirconia ceramic with a surface compounded with a bioactive substance and a preparation method thereof. The method comprises the following steps: preparing calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive sol; preparing a zirconium oxide suspension; preparing a zirconia ceramic having a porous surface layer; putting the zirconia ceramic with the porous surface layer into calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive sol by a negative pressure infiltration process, so that the bioactive sol is infiltrated into the porous surface layer, and carrying out heat treatment after drying to obtain the ceramic. According to the invention, calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances are loaded in the pore channels of the porous surface layer of the zirconia to endow the zirconia ceramic with high bioactivity, and the porous surface layer is combined with the zirconia ceramic and synchronously sintered, so that the problem of poor interface bonding strength of a surface active layer and a zirconia matrix material is solved; the bioactive substances only permeate into the porous surface layer, the internal matrix still keeps high density after sintering, and the mechanical property of the material is not obviously influenced.

Description

A kind of modified zirconia ceramic with surface composite bioactive substance and preparation method thereof

technical field

The invention relates to the field of dental restoration medical materials, in particular to a modified zirconia ceramic with surface composite biological active substances and a preparation method thereof.

Background technique

Titanium and titanium alloy implants in metal implants have been widely used in clinical treatment of tooth loss caused by dental caries, periodontitis and dental trauma. However, there are also problems such as blackening of titanium metal caused by gingival recession and allergy caused by the release of toxic ions. Zirconia ceramics have good biocompatibility and chemical stability, excellent mechanical properties and unique aesthetic effects and become a dental restoration material with good clinical application prospects. As an inert material, zirconia ceramics have no biological activity. When implanted in the body, the surrounding fibrous tissue will hinder the integration of the implant and the surrounding bone tissue, resulting in implant failure. Therefore, a biologically active zirconia dental restoration is developed. Materials are important.

In recent years, the surface modification of modified zirconia is generally carried out by the coating method, but the thermal expansion coefficient mismatch problem generally exists in the coating method, which leads to the existence of residual stress, which makes the interface between the substrate and the coating weak. Dissolving and falling off, not suitable for clinical application, and the current surface modification methods will lead to phase transition and seriously affect the mechanical strength of zirconia ceramics, and the amount of biologically active substances added and the types of active substances are limited, which can improve the biological performance. limited. CN112028626A discloses the preparation method of zirconia bioactive ceramics. Due to the mismatch between the thermal expansion coefficient of the coating and the substrate, the residual stress is present, which is manifested as poor bonding, which may cause the coating to fall off in long-term application. CN106904962B discloses a preparation method of a biologically active zirconia dental ceramic material, the active substances existing at the grain boundaries affect the mechanical properties of the zirconia, and the addition amount of the active substances is limited. CN109867520A discloses a zirconia-based strontium, silicon and fluorine micro-doped hydroxyapatite zirconia toughened composite coating and its preparation method and application. There is also the problem that the coating falls off due to insufficient bonding. CN110917394A discloses the application of ion-modified zirconia surface in the preparation of zirconia abutments or implants, but there is also the problem that the coating falls off due to insufficient bonding. Silver ion-modified zirconia improved the antibacterial properties, but did not promote cell proliferation and differentiation.

Calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances have a stimulating effect on the gene expression of osteoblasts, and can significantly promote bone regeneration in clinical applications. Calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances have good biological activity, biocompatibility, biodegradability and mechanical properties, release active ions such as calcium, magnesium, silicon, phosphorus, etc., which can induce the formation of apatite layer, Conducive to the combination of material and bone tissue. The deposition of wollastonite in porous alumina ceramics can significantly improve its biological activity and can mineralize apatite. Diopside scaffolds induce apatite production and support human osteoblast adhesion, growth, and alkaline phosphatase (ALP) expression. Therefore, it is of great significance to develop a zirconia dental ceramic with high biological activity, high strength, and high bonding strength between the surface modified layer and the substrate.

SUMMARY OF THE INVENTION

In order to overcome the shortcomings and deficiencies that the conventional biologically modified zirconia dental ceramics in the prior art cannot have both excellent biological activity and high mechanical strength, the object of the present invention is to provide a modified zirconia ceramic with surface composite biologically active substances and its preparation method. The zirconia ceramic material has good biological activity, high mechanical properties and simple preparation process.

The object of the present invention is achieved by at least one of the following technical solutions.

In the preparation method provided by the present invention, the calcium-magnesium-silicon or calcium-silicon-phosphorus biologically active sol is attached to the pores of the zirconia porous surface layer, and after high-temperature heat treatment, the generated calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances are embedded in the zirconia. In the surface pores, the zirconia ceramics are endowed with high biological activity. The porous surface layer is combined with the zirconia ceramic and fired simultaneously, which solves the problem of poor bonding strength between the surface active layer and the zirconia matrix material; while the biologically active material only penetrates into the porous surface layer, and the internal matrix remains high after sintering. The density and mechanical properties of the material are not significantly affected, which can solve the problem that conventional biologically modified zirconia dental ceramics cannot have good biological activity and high mechanical strength at the same time.

The preparation method of modified zirconia ceramics with surface composite biologically active substances provided by the present invention comprises the following steps:

(1) Preparation of calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive sol: add hydrolyzable silicon-containing compound, water-soluble calcium salt, water-soluble magnesium salt or water-soluble phosphorus salt into deionized water, mix well, obtain a mixed solution, adjust The pH of the mixed solution is 6.0-8.0, and the hydrolysis and polycondensation reaction is carried out to obtain calcium magnesium silica sol or calcium silica phosphorus sol;

(2) pressing and molding the zirconia powder to prepare a green zirconia ceramic body, and heating up to perform a pre-sintering treatment to obtain a zirconia ceramic pre-sintered body;

(3) Preparation of zirconia suspension: adding pore-forming agent, stabilizer, dispersant and zirconia powder into the solvent, mixing uniformly to obtain suspension; Zirconium suspension) is dipped (dipping and pulling process) or sprayed on the surface of the zirconia ceramic pre-sintered body described in step (2) (the surface of the pre-sintered body is infiltrated with the adsorption suspension), dried to form a pore-forming surface layer, and the temperature is raised to carry out Sintering to obtain a zirconia ceramic with a porous surface layer;

(4) In the container, soak the zirconia ceramic with porous surface layer described in step (3) in the calcium magnesium silica sol or calcium silicon phosphorus sol prepared in step (1), and carry out negative pressure infiltration treatment (by negative pressure Infiltration treatment, infiltrating calcium magnesium silicon or calcium silicon phosphorus bioactive sol into the porous surface layer of zirconia ceramics), taking out, standing for aging, and drying to obtain zirconia ceramics with composite surface layers; The compounded zirconia ceramics are heated at a temperature to obtain the modified zirconia ceramics with the surface compounded with bioactive substances (zirconia dental ceramics with high bioactivity and high strength).

Further, the silicon-containing compound described in step (1) is at least one of ethyl orthosilicate, silicon acetate, and methyl silicate;

Further, the calcium salt described in step (1) is at least one of calcium nitrate, calcium chloride, calcium acetate, and calcium citrate;

Further, the magnesium salt described in step (1) is at least one of magnesium nitrate, magnesium chloride, magnesium acetate, and magnesium citrate;

Further, the phosphorus salt described in step (1) is at least one of sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, ammonium phosphate, ammonium hydrogen phosphate, and ammonium dihydrogen phosphate. kind.

Further, the mixed solution described in step (1), in parts by mass, comprises:

Further, the hydrolysis and polycondensation reaction time of step (1) is 24-48h.

Further, the pressure of the compression molding in step (2) is 100-220MPa, and the compression molding time is 2-30min;

Preferably, the pressing and forming in step (2) includes: filling the zirconia powder into a plastic mold, and then molding with an isostatic press after sealing.

Further, the temperature of the pre-sintering treatment in step (2) is 500-1000° C., the time of the pre-sintering treatment is 0.5-3 h, and the heating rate is 2-10° C./min.

Further, the pore-forming agent described in step (3) is polyethyl acrylate microspheres, polylactic acid-glycolic acid copolymer microspheres, polyacrylic acid microspheres and polystyrene microspheres, polymethyl methacrylate microspheres, At least one of the graphite microspheres, the particle size of the pore-forming agent is 1-20 μm;

Further, the stabilizer in step (3) is at least one of polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl butyral, and glycerin;

Further, the dispersant in step (3) is at least one of polyethylene glycol, polyacrylic acid, and polymethacrylate ammonia;

Further, the solvent in step (3) is at least one of water and absolute ethanol.

Further, the suspension described in step (3), in parts by mass, comprises:

Further, the drying temperature in step (3) is 60-100°C, and the drying time is 6-12h;

Further, the thickness of the pore-forming surface layer in step (3) is 10-80 μm;

Preferably, the thickness of the pore-forming surface layer in step (3) is 20-80 μm.

Preferably, the average pore size of the pore-forming surface layer in step (3) is 0.1-50 μm, and the porosity is 20%-70%.

Further, the temperature of the sintering treatment in step (3) is 1300-1600°C, the sintering treatment time is 2-4h, and the heating rate is 2-10°C/min.

Preferably, the dipping in step (3) includes: dipping the zirconia ceramic pre-sintered body in a zirconia suspension for a duration of 10s-2min, and quickly pulling it out from the suspension 1 after dipping.

Preferably, the spraying in step (3) comprises: spraying the suspension 1 on the zirconia ceramic pre-sintered body, the spraying pressure is 0.2MPa, and the spraying time is 0.5-4min.

Preferably, the zirconia powder in steps (2) and (3) is a partially stabilized tetragonal zirconia powder using any one or more of Y2O3, MgO, CaO, La2O3 as a stabilizer.

Further preferably, the zirconia powder in steps (2) and (3) is yttria-stabilized zirconia powder.

Further, the osmotic pressure of the negative pressure osmotic treatment in step (4) is 0～-0.2MPa, and the time of the negative pressure osmotic treatment is 10s-80min;

Further, the time for standing and aging in step (4) is 6-48h; the drying temperature in step (4) is 60-180°C, and the drying time is 12-72h;

Preferably, the drying temperature in step (4) is 60-100°C.

Further, the temperature of the heat treatment in step (4) is 600-1300°C, the heat treatment time is 0.5-4h, and the heating rate is 2-10°C/min.

The present invention provides a modified zirconia ceramic prepared by the above-mentioned preparation method, the surface of which is composited with biologically active substances.

In the present invention, calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive sol is infiltrated into the inside of zirconia pores with a porous surface layer structure, the sol is converted into gel after drying at low temperature, and then heat-treated at high temperature to generate calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances , Partial liquid phase or solid phase diffusion occurs during the high temperature sintering process to ensure that there is a certain bonding strength between the calcium magnesium silicon or calcium silicon phosphorus bioactive substances and zirconia and are embedded in the interior of the non-straight pores, ensuring the bioactive substances. It will not fall off from the pores, giving zirconia high biological activity.

In the preparation method provided by the invention, calcium magnesium silicon or calcium silicon phosphorus bioactive substances are generated after the low temperature drying and high temperature heat treatment of the sol. One or more of calcium-magnesium-silicon bioactive crystalline substances such as tobermorite and tobermorite or calcium-silicon-phosphorus bioactive glass substances, the presence of bioactive substances endows zirconia with high bioactivity. The porous surface layer structure and zirconia ceramics are fired simultaneously, and the materials are consistent, which solves the problem of poor bonding strength between the surface active layer and the zirconia matrix material interface, and can control the porosity, pore size and thickness of the porous surface layer structure. The porous surface layer structure can penetrate various active substances and is not limited by the types of active substances. It has certain social and economic value for improving the restoration effect of dental ceramics and promoting its wider clinical application.

Compared with the prior art, the present invention has the following advantages and beneficial effects:

(1) The preparation method provided by the present invention is the first time to construct a porous zirconia layer on the surface of a zirconia ceramic with a dense structure. The thickness, pore size and porosity of the porous zirconia layer can be adjusted arbitrarily, while the inner dense structure of the zirconia ceramic guarantees In order to ensure that the dental ceramics have excellent mechanical strength, the pores of the porous zirconia surface layer are loaded with calcium magnesium silicon or calcium silicon phosphorus biologically active substances. Calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances have a stimulating effect on the gene expression of osteoblasts, can significantly promote bone regeneration in clinical applications, stimulate the gene expression of osteoblasts, and can significantly promote bone regeneration in clinical applications. regeneration. Calcium-magnesium-silicon or calcium-silicon-phosphorus bioactive substances have good biological activity, biocompatibility, biodegradability, and mechanical properties, and release active ions such as calcium, magnesium, silicon, and phosphorus, which can induce the formation of apatite layers, which is beneficial to Binding of material to bone tissue.

(2) The modified zirconia dental ceramics prepared by the present invention with surface composite bioactive substances can be immersed in simulated body fluid for a period of time, and weakly crystalline hydroxyapatite can be mineralized on the surface, which is an inorganic substance in bone tissue. , so the biological activity is significantly improved;

(3) The porous zirconia surface layer prepared by the present invention can penetrate various active sols, and is not limited by components, and is not limited to certain or certain types of biologically active sols. By adjusting the thickness, pore size and porosity of the zirconia porous surface layer, the penetration amount of the bioactive sol can be adjusted, which can significantly improve the bioactivity of dental ceramics;

(4) In the preparation method provided by the present invention, the involved zirconia ceramic surface modification treatment method is implemented on the pre-sintered body after the zirconia ceramic is formed and processed, so as to avoid the high hardness, The high density makes it difficult to process, and no special equipment is required, the production method is simple, the yield is high, and the cost is low;

(5) The bioactive coating prepared on the surface of the zirconia ceramic dense sintered body in the prior art has problems such as poor interfacial bonding and easy peeling and dissolution in a complex oral environment. Compared with the porous surface prepared by the present invention The porous surface layer of the zirconia ceramic layer and the inner matrix are the same material, so the prepared bioactive surface layer and the zirconia ceramic are an integrated material, and there is no residual stress problem caused by the mismatch of thermal expansion coefficients. The combination of bone tissue is more stable and firm, and it can maintain long-term stable biological activity, and the clinical long-term treatment effect is better.

Description of drawings

FIG. 1 is a cross-sectional microstructure result diagram of the modified zirconia ceramics with surface composite bioactive substances prepared in Examples 1-4.

2 is a graph showing the results of the surface microstructure of the modified zirconia ceramics whose surface is compounded with biologically active substances of Example 1.

3 is a graph showing the results of the microstructure of the modified zirconia ceramic with the surface composite bioactive material of Example 1 after 7 days of SBF simulated body fluid mineralization.

4 is a graph showing the results of the microstructure of the modified zirconia ceramic with the surface-composite bioactive material of Example 2 after 7 days of SBF simulated body fluid mineralization.

5 is a graph showing the results of the microstructure of the modified zirconia ceramics with surface-composite biologically active substances of Example 3 after 7 days of mineralization in SBF simulated body fluid.

Figure 6 is a graph showing the results of cell proliferation for 1 day and 3 days of co-culture of modified zirconia ceramics with surface-complexed bioactive substances and zirconia ceramics without any modification treatment with mouse bone marrow mesenchymal stem cells for 1 to 3 days .

Figure 7 shows the results of ALP quantification in the co-culture of the modified zirconia ceramics with bioactive substances on the surface of the implementations 1 to 3 and the zirconia ceramics without any modification treatment and mouse bone marrow mesenchymal stem cells for 7 days and 14 days .

Detailed ways

The specific implementation of the present invention will be further described below with reference to examples, but the implementation and protection of the present invention are not limited thereto. It should be pointed out that, if there are any processes that are not described in detail below, those skilled in the art can realize or understand them with reference to the prior art. If the reagents or instruments used do not indicate the manufacturer, they are regarded as conventional products that can be purchased in the market.

Example 1

(1) Preparation of calcium-magnesium-silicon biologically active sol: add 10g of ethyl orthosilicate, 20g of calcium nitrate, and 30g of magnesium nitrate in 50g of deionized water, mix well to obtain a mixed solution, adjust the pH of the mixed solution to 8.0, and make it happen Hydrolysis and polycondensation reaction (reaction time is 12h) to form calcium magnesium silica sol;

(2) The yttria-stabilized zirconia powder is press-molded, the pressure of the press-molding is 220MPa, and the press-molding time is 2min to prepare a green zirconia ceramic body, and the pre-sintering treatment is carried out under the condition that the temperature is raised to 500°C, The pre-sintering treatment time is 2h, and the heating rate is 10°C/min to obtain a zirconia ceramic pre-sintered body;

(3) Preparation of zirconia suspension: polyethyl acrylate microspheres, polyvinyl alcohol, polyacrylic acid, deionized water and zirconia powder are mixed according to the mass ratio of 10:10:2:53:25, and the mixture is uniformly stirred. Preparation of suspension 1 (high stability and high dispersity zirconia suspension);

(4) Immerse the suspension 1 prepared in step (3) on the surface of the zirconia ceramic pre-sintered body prepared in step (2) by dipping and pulling process, and the dipping time is 10s. After the porous surface layer infiltrates and adsorbs the zirconia suspension , dried at 60°C for 12h to form a pore-forming surface layer (thickness of 10um), and then heated to 1350°C for sintering for 2h at a rate of 5°C/min to obtain a zirconia ceramic with a porous surface layer;

(5) Through the negative pressure infiltration process, the osmotic pressure is 0.1 MPa, and the infiltration time is 10 s, and the zirconia ceramics with porous surface layer prepared in step (4) is dipped in the calcium-magnesium-silicon bioactive sol prepared in step (1). Infiltration, the calcium-magnesium-silicon bioactive sol suspension infiltrated into the porous surface layer of zirconia ceramics, taken out, left to stand for 6 hours, and dried at a temperature of 60 °C for 12 hours to obtain a porous surface layer composite calcium-magnesium-silicon biological Active sol zirconia ceramics;

(6) Heat the zirconia ceramics prepared in step (5) to 1300°C for heat treatment at 1300°C for 10°C/min, to obtain the modified surface composite bioactive material. Zirconia ceramics (high-strength zirconia dental ceramics with high bioactivity).

Part a of Fig. 1 is the cross-sectional microstructure result of the modified zirconia ceramic with the surface composite bioactive material prepared in Example 1; it can be seen from Fig. 1 that the porous surface layer is closely combined with the zirconia matrix, and the thickness of the porous surface layer is about is 10 μm.

2 is a graph showing the results of the surface microstructure of the modified zirconia ceramics whose surface is compounded with biologically active substances of Example 1. It can be seen from Figure 2 that the pore size distribution of the porous surface layer is relatively uniform and the porosity is relatively high.

The modified zirconia ceramics prepared in this example with surface composite bioactive substances have high biological activity. As shown in FIG. 3 , the modified zirconia ceramics are soaked in 1.0 times of simulated body fluid (Simulated Body Fluid, SBF). After 8 days, abundant cluster-like crystals appeared on the surface of the samples after the surface layer was infiltrated with the calcium-magnesium-silicon bioactive sol, indicating that the bioactivity of the modified zirconia ceramics was significantly improved.

The mechanical properties test (refer to the national standard GB/T 6569-86) shows that the flexural strength of the modified zirconia ceramics with bioactive substances on the surface is 1100MPa, and the thickness of the surface porous layer is 10μm. Under the premise of ensuring the excellent mechanical properties of the product, the biological activity of the preparation method provided in the embodiment of the present invention is improved to a certain extent.

Example 2

(1) Preparation of calcium magnesium silicon bioactive sol: add 10g ethyl orthosilicate, 20g calcium nitrate, 30g magnesium citrate in 50g deionized water, mix well to obtain a mixed solution, adjust the pH of the mixed solution to 8.0, and make it happen Hydrolysis and polycondensation reaction (reaction time is 24h) to form calcium magnesium silica sol;

(2) The yttria-stabilized zirconia powder is press-molded, the pressure of press-molding is 100MPa, and the time of press-molding is 30min, to prepare a green zirconia ceramic body, and pre-sintering is carried out under the condition that the temperature is raised to 500°C, The pre-sintering treatment time is 2h, and the heating rate is 2°C/min to obtain a zirconia ceramic pre-sintered body;

(3) Preparation of zirconia suspension: polyethyl acrylate microspheres, polyvinyl alcohol, polyacrylic acid, deionized water and zirconia powder are mixed according to the mass ratio of 10:10:2:53:25, and the mixture is uniformly stirred. Preparation of suspension 1 (high stability and high dispersity zirconia suspension);

(4) Immerse the suspension 1 prepared in step (3) on the surface of the zirconia ceramic pre-sintered body prepared in step (2) by dipping and pulling process, and the dipping time is 20s. After the porous surface layer infiltrates and adsorbs the zirconia suspension , dried at 60 °C for 12 h to form a pore-forming surface layer (thickness of 10 μm), and then heated to 1350 °C for sintering for 2 h at a rate of 5 °C/min to obtain a zirconia ceramic with a porous surface layer;

(5) Through the negative pressure infiltration process, the osmotic pressure is 0.1 MPa, and the infiltration time is 10 s, and the zirconia ceramics with porous surface layer prepared in step (4) is dipped in the calcium-magnesium-silicon bioactive sol prepared in step (1). Infiltration, the calcium-magnesium-silicon bioactive sol penetrated into the porous surface layer of zirconia ceramics, taken out, left to age for 6 hours, and dried at a temperature of 60 °C for 12 hours to obtain a porous surface layer composite calcium-magnesium-silicon bioactive material zirconia ceramics;

(7) heating the zirconia ceramic prepared in step (6) to 1300°C for heat treatment at 1300°C for 10°C/min to obtain the surface composite calcium-magnesium-silicon bioactive sol. Substances of modified zirconia ceramics (high-strength zirconia dental ceramics with high bioactivity).

Part b of Fig. 1 is the cross-sectional microstructure result of the modified zirconia ceramic with surface composite bioactive material prepared in Example 2; it can be seen from Fig. 1 that the porous surface layer is closely combined with the zirconia matrix, and the thickness of the porous surface layer is about is 15 μm.

The modified zirconia ceramics prepared in this example with surface composite bioactive substances have high biological activity. As shown in FIG. 4 , the modified zirconia ceramics are soaked in 1.0 times of simulated body fluid (Simulated Body Fluid, SBF). After 8 days, abundant cluster-like crystals appeared on the surface of the samples after the surface layer was infiltrated with the calcium-magnesium-silicon bioactive sol, indicating that the bioactivity of the modified zirconia ceramics was significantly improved.

After the mechanical property test (refer to the national standard GB/T 6569-86), it is concluded that the flexural strength of the modified zirconia ceramics with bioactive substances on the surface is 1050MPa, and the thickness of the surface porous layer is 15μm. Under the premise of ensuring the excellent mechanical properties of the product, the biological activity of the preparation method provided in the embodiment of the present invention is improved to a certain extent.

Example 3

(1) Preparation of calcium-silicon-phosphorus bioactive sol: add 31g of ethyl orthosilicate, 29g of calcium nitrate, and 20g of sodium phosphate in 20g of deionized water, mix well to obtain a mixed solution, adjust the pH of the mixed solution to 8.0, and make it hydrolyzed Polycondensation reaction (reaction time is 24h) to form calcium-silicon-phosphorus sol;

(2) The yttria-stabilized zirconia powder is press-molded, the pressure of press-molding is 180MPa, and the time of press-molding is 10min, to prepare a zirconia ceramic green body, and pre-sintering is carried out under the condition that the temperature is raised to 500°C, The pre-sintering treatment time is 2h, and the heating rate is 5°C/min to obtain a zirconia ceramic pre-sintered body;

(3) Preparation of zirconia suspension: polyethyl acrylate microspheres, polyvinyl alcohol, polyacrylic acid, deionized water and zirconia powder are mixed according to the mass ratio of 10:10:2:53:25, and the mixture is uniformly stirred. Preparation of suspension 1 (high stability and high dispersity zirconia suspension);

(4) Immerse the suspension 1 prepared in step (3) on the surface of the zirconia ceramic pre-sintered body prepared in step (2) by dipping and pulling process, and the dipping time is 20s. After the porous surface layer infiltrates and adsorbs the zirconia suspension , dried at 60°C for 12h to form a pore-forming surface layer (thickness of 10um), and then heated to 1350°C for sintering for 2h at a rate of 5°C/min to obtain a zirconia ceramic with a porous surface layer;

(5) Through the negative pressure infiltration process, the osmotic pressure is 0.1MPa, and the infiltration time is 10s, and the zirconia ceramics with porous surface layer prepared in step (4) is dipped in the calcium-silicon-phosphorus bioactive sol prepared in step (1). Infiltration, the calcium-magnesium-silicon bioactive sol penetrated into the porous surface layer of zirconia ceramics, taken out, left to age for 6 hours, and dried at a temperature of 60 °C for 12 hours to obtain a porous surface layer composite calcium-magnesium-silicon bioactive material zirconia ceramics;

(6) heating the zirconia ceramics prepared in step (5) to 800°C for 0.5 h, and the heating rate is 10°C/min, to obtain the surface composite calcium-phosphorus-silicon bioactive sol. Substances of modified zirconia ceramics (high-strength zirconia dental ceramics with high bioactivity).

Part c of Fig. 1 is the cross-sectional microstructure result of the modified zirconia ceramic with surface composite bioactive material prepared in Example 3; it can be seen from Fig. 1 that the porous surface layer is closely combined with the zirconia matrix, and the thickness of the porous surface layer is about is 25 μm.

The modified zirconia ceramics with the surface composite biologically active substances prepared in this example have high biological activity. As shown in FIG. 5 , the modified zirconia ceramics were soaked in 1.0 times of simulated body fluid (Simulated Body Fluid, SBF). After 8 days, abundant cluster-like crystals appeared on the surface of the samples after the surface layer was infiltrated with the calcium-magnesium-silicon bioactive sol, indicating that the bioactivity of the modified zirconia ceramics was significantly improved.

The mechanical properties test (refer to the national standard GB/T 6569-86) shows that the flexural strength of the modified zirconia ceramics with bioactive substances on the surface is 1120MPa, and the thickness of the surface porous layer is 25μm. Under the premise of ensuring the excellent mechanical properties of the product, the biological activity of the preparation method provided in the embodiment of the present invention is improved to a certain extent.

Example 4

(1) Preparation of calcium-silicon-phosphorus bioactive sol: add 31g of ethyl orthosilicate, 34g of calcium nitrate and 15g of sodium phosphate in 20g of deionized water, mix well to obtain a mixed solution, adjust the pH of the mixed solution to 8.0, and make it hydrolyzed Polycondensation reaction (reaction time is 24h) to form calcium-silicon-phosphorus sol;

(2) The yttria-stabilized zirconia powder is press-molded, the pressure of press-molding is 200MPa, and the time of press-molding is 10min, to prepare a green zirconia ceramic body, and pre-sintering is carried out under the condition that the temperature is raised to 500°C, The pre-sintering treatment time is 2h, and the heating rate is 5°C/min to obtain a zirconia ceramic pre-sintered body;

(3) Preparation of zirconia suspension: polyethyl acrylate microspheres, polyvinyl alcohol, polyacrylic acid, deionized water and zirconia powder are mixed according to the mass ratio of 10:5:2:53:30, and the mixture is uniformly stirred. Preparation of suspension 1 (high stability and high dispersity zirconia suspension);

(4) Immerse the suspension 1 prepared in step (3) on the surface of the zirconia ceramic pre-sintered body prepared in step (2) by dipping and pulling process, and the dipping time is 20s. After the porous surface layer infiltrates and adsorbs the zirconia suspension , dried at 60°C for 12h to form a pore-forming surface layer (thickness of 10um), and then heated to 1350°C for sintering for 2h at a rate of 5°C/min to obtain a zirconia ceramic with a porous surface layer;

(5) through the negative pressure infiltration process, the osmotic pressure is 0.1MPa, and the infiltration time is 10s, the zirconia ceramics with porous surface layer prepared in step (4) is immersed in the calcium-phosphorus-silicon bioactive sol prepared in step (1) Infiltration, the calcium-phosphorus-silicon bioactive sol penetrated into the porous surface layer of the zirconia ceramics, taken out, left to age for 6 hours, and dried at a temperature of 60 °C for 12 hours to obtain a porous surface layer composite calcium-magnesium-silicon bioactive material zirconia ceramics;

(6) Heat the zirconia ceramics prepared in step (5) to 900°C for 0.5 h, and the heating rate is 10°C/min, to obtain the surface composite calcium-phosphorus-silicon bioactive sol. Substances of modified zirconia ceramics (high-strength zirconia dental ceramics with high bioactivity).

Part d of Fig. 1 is the cross-sectional microstructure result of the modified zirconia ceramic with surface composite bioactive material prepared in Example 4; it can be seen from Fig. 1 that the surface porous layer is closely combined with the zirconia matrix, and the thickness of the porous layer is about 35μm.

The modified zirconia ceramics prepared in this example with surface-composite biologically active substances have higher biological activity. After the modified zirconia ceramics were soaked in 1.0 times of simulated body fluid (Simulated Body Fluid, SBF) for 8 days, the surface layer infiltrated Abundant cluster-like crystals appeared on the surface of the samples after the calcium magnesium silicon bioactive sol, indicating that the bioactivity of the modified zirconia ceramics has been significantly improved, as shown in Figure 3-Figure 5.

After the mechanical property test (refer to the national standard GB/T 6569-86), it is concluded that the flexural strength of the modified zirconia ceramic with the surface composite bioactive material is 1150MPa, and the thickness of the surface porous layer is 35um. Under the premise of ensuring the excellent mechanical properties of the product, the biological activity of the preparation method provided in the embodiment of the present invention is improved to a certain extent.

cell experiment

Determination of cell proliferation: Under sterile conditions, the modified zirconia ceramics prepared in Examples 1-3 with calcium-phosphorus-silicon bioactive substances on the surface and the zirconia ceramics without any modification treatment were first subjected to high temperature and high pressure sterilization. The bacteria were then dried to obtain zirconia ceramic samples (respectively marked as Example 1 sample, Example 2 sample, Example 3 sample, and blank group sample). Then each zirconia ceramic sample was put into a 48-well plate, soaked in complete medium for 6 hours, and then the complete medium was aspirated. The number of cells per well was 10,000, and the culture process was changed to complete medium every other day. When the cells were cultured for 1 d and 3 d, the activity expression of alkaline phosphatase in osteogenic differentiation was determined.

Determination of the expression of alkaline phosphatase: Under sterile conditions, the modified zirconia ceramics prepared in Examples 1-3 with calcium-phosphorus-silicon bioactive substances on the surface and the zirconia ceramics without any modification treatment were first subjected to high temperature Autoclave and then dry to obtain zirconia ceramic samples (respectively marked as Example 1 sample, Example 2 sample, Example 3 sample, and blank group sample). Then each zirconia ceramic sample was put into a 48-well plate, soaked in complete medium for 6 hours, and then the complete medium was aspirated. The number of cells in each well was 20,000, and the osteoinductive solution was replaced every other day during the culture. When the cells were cultured for 7d and 14d, the activity expression of alkaline phosphatase in osteogenic differentiation was determined.

The preparation of the above-mentioned zirconia ceramics without any modification treatment includes: zirconia ceramics pre-sintered body and calcination treatment. Wherein, the zirconia ceramic pre-sintered body can be carried out by referring to step (2) of Example 1 to obtain a zirconia ceramic pre-sintered body, and then the zirconia ceramic pre-sintered body is subjected to a calcination treatment, and the calcination treatment is: raising the temperature to 1300° C. The heat treatment was carried out for 0.5 h under the conditions, and the heating rate was 10 °C/min.

Figure 6 is a graph showing the results of cell proliferation for 1 day and 3 days of co-culture of modified zirconia ceramics with surface-complexed bioactive substances and zirconia ceramics without any modification treatment with mouse bone marrow mesenchymal stem cells for 1 to 3 days .

It can be seen from Figure 6 that the modified zirconia ceramics prepared in the example with the surface composite bioactive substances co-cultured with mouse bone marrow mesenchymal stem cells for 1 day and 3 days have a better cell proliferation effect than the zirconia ceramics without any modification treatment. Even better, cell proliferation has been significantly improved.

After 7 days and 14 days of co-culture, the mouse bone marrow mesenchymal stem cells in each sample group were collected and detected using the ALP quantitative kit. Figure 7 shows the results of ALP quantification in the co-culture of the modified zirconia ceramics with bioactive substances on the surface of the implementations 1 to 3 and the zirconia ceramics without any modification treatment and mouse bone marrow mesenchymal stem cells for 7 days and 14 days .

It can be seen from Figure 7 that the osteogenic differentiation effect of the modified zirconia ceramics with the surface composite bioactive substances and the mouse bone marrow mesenchymal stem cells co-cultured for 7 days and 14 days is better than that of the zirconia ceramics without any modification treatment. The effect is better, and the osteogenic differentiation of cells has been significantly improved. The blank group in Figures 6 and 7 represents the zirconia ceramics without any modification treatment, and 1, 2, and 3 represent the samples of Example 1, Example 2, and Example 3, respectively.

The above examples are only preferred embodiments of the present invention, and are only used to explain the present invention, but not to limit the present invention. Changes, substitutions, modifications, etc. made by those skilled in the art without departing from the spirit of the present invention shall belong to the present invention. the scope of protection of the invention.

Claims (9)

1. a preparation method of the modified zirconia ceramics of surface composite biological active material, is characterized in that, comprises the steps: (1) Add silicon-containing compound, calcium salt, magnesium salt or phosphorus salt into water, mix evenly to obtain a mixed solution, adjust the pH of the mixed solution to 6.0-8.0, and carry out hydrolysis and polycondensation reaction to obtain calcium-magnesium-silica sol or calcium-silicon-phosphorus sol; (2) Pressing the zirconia powder into a shape, heating up and performing pre-sintering treatment to obtain a zirconia ceramic pre-sintered body; (3) Add pore-forming agent, stabilizer, dispersing agent and zirconia powder into the solvent, and mix them evenly to obtain a suspension; dipping or spraying the suspension on the zirconia ceramic pre-sintered body in step (2) On the surface of the product, dry to form a pore-forming surface layer, and heat up to perform sintering treatment to obtain a zirconia ceramic with a porous surface layer; (4) Immerse the zirconia ceramic with a porous surface layer described in step (3) in the calcium magnesium silica sol or calcium silicon phosphorus sol prepared in step (1), carry out negative pressure infiltration treatment, take out, stand for aging, drying to obtain a composite zirconia ceramic on the surface layer; heating the composite zirconia ceramic on the surface layer to perform heat treatment to obtain the modified zirconia ceramic with the surface composite biologically active material. 2 . The method for preparing modified zirconia ceramics with surface composite biologically active substances according to claim 1 , wherein the silicon-containing compound in step (1) is ethyl orthosilicate, silicon acetate, methyl silicate at least one of esters; the calcium salt in step (1) is at least one of calcium nitrate, calcium chloride, calcium acetate, and calcium citrate; the magnesium salt in step (1) is magnesium nitrate, magnesium chloride, magnesium acetate, At least one of magnesium citrate; the phosphorus salt in step (1) is sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, ammonium phosphate, ammonium hydrogen phosphate, dibasic phosphate At least one of ammonium hydrogen. 3 . The preparation method of modified zirconia ceramics with surface composite bioactive substances according to claim 1 , wherein the hydrolysis and polycondensation reaction time in step (1) is 24-48 h. 4 . 4 . The method for preparing modified zirconia ceramics with surface composite biologically active substances according to claim 1 , wherein the pressing pressure in step (2) is 100-220 MPa, and the pressing time is 2 MPa. 5 . -30min; the temperature of the pre-sintering treatment is 500-1000°C, the time of the pre-sintering treatment is 0.5-3h; the heating rate is 2-10°C/min. 5 . The preparation method of modified zirconia ceramics with surface composite bioactive substances according to claim 1 , wherein the pore-forming agent in step (3) is polyethyl acrylate microspheres, polylactic acid-glycolic acid At least one of copolymer microspheres, polyacrylic acid microspheres, polystyrene microspheres, polymethyl methacrylate microspheres, and graphite microspheres, wherein the particle size of the pore-forming agent is 1-20 μm; step (3) ) the stabilizer is at least one of polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl butyral, and glycerin; the dispersant in step (3) is at least one of polyethylene glycol and polyacrylic acid; In step (3), the solvent is at least one of water and absolute ethanol. 6 . The method for preparing modified zirconia ceramics with surface composite biologically active substances according to claim 1 , wherein the suspension in step (3), in parts by mass, comprises: 7 . Pore-forming agent 0.5-10 copies; Stabilizer 5-40 copies; 0.1-2 parts of dispersant; 15-40 parts of zirconia powder; Solvent 20-50 parts. 7 . The method for preparing modified zirconia ceramics with surface composite biologically active substances according to claim 1 , wherein the drying temperature in step (3) is 60-100° C., and the drying time is 6-12 . h; the thickness of the pore-forming surface layer in step (3) is 20-80 μm; the temperature of the sintering treatment in step (3) is 1300-1600 ° C, the sintering treatment time is 2-4 h, and the heating rate is 2-10 °C/min. 8 . The method for preparing modified zirconia ceramics with surface composite biologically active substances according to claim 1 , wherein the osmotic pressure of the negative pressure osmotic treatment in step (4) is 0-0.2 MPa, and the negative pressure The time of infiltration treatment is 10s-80min; the time for standing and aging in step (4) is 6-48h; the drying temperature in step (4) is 60-180°C, and the drying time is 12-72h; step (4) The heat treatment temperature is 600-1300°C, the heat treatment time is 0.5-4h, and the heating rate is 2-10°C/min. 9 . A modified zirconia ceramic with a surface composite biologically active material prepared by the preparation method according to any one of claims 1 to 8 . 10 .

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