Implant, manufacturing method therefor, and use thereof

Abstract

Provided are an implant, a manufacturing method therefor, and the use thereof. The implant comprises a material body, a metal oxide layer and a mixed crystalline layer, the mixed crystalline layer being provided on a surface of the metal oxide layer. The metal oxide layer comprises a metal oxide nanorod array, the metal oxide being selected from zinc oxide, silver oxide or a combination thereof. The mixed crystalline layer comprises a CaP crystal and a metal oxide crystal. The implant uses the physical puncturing of the metal oxide nanorods and antibacterial metal ions generated by degradation of same for sterilization, and has good antibacterial effect on both gram-positive bacteria and gram-negative bacteria, thereby preventing infections; and the implant can relieve post-implantation inflammatory responses and reduce immune responses in the case of post-implantation infections, thereby shortening the time for wound healing. In addition, the coating effect of the mixed crystalline layer on the metal oxide layer enables sustained release of the antibacterial metal ions and enables the release time to be long, thus achieving long-lasting antibacterial performance.

Description

Implant and its preparation method and application Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to an implant and a preparation method and application thereof. Background Art

[0002] Superhydrophilic implants, defined as surfaces where a water droplet has a contact angle of less than 10°, are highly wettable. They are a rapidly developing new class of oral implants, based on titanium implants and characterized by a superhydrophilic surface achieved through various surface functionalization methods. Compared to traditional hydrophobic titanium implants, superhydrophilicity imparts faster blood adsorption, promoting the osteogenic differentiation of stem cells around the implant, shortening post-implant bone healing time, and enhancing implant osseointegration, making them particularly suitable for patients with poor bone quality.

[0003] Existing methods for preparing super-hydrophilic implants mainly include: ① Large-particle sandblasting and acid etching: Using corundum particles of about 0.25-0.5mm to impact the implant surface with a high-speed airflow under high pressure, forming holes equivalent to bone pits. The implant is then placed in a mixture of high-temperature hydrochloric acid and sulfuric acid for acid etching, etching the oxide film on the metal surface to increase hydrophilicity. The large-particle sandblasting and acid etching work together to produce a multi-dimensional structure suitable for the attachment of osteoblasts and fibrinogen. ② Anodic oxidation technology: The implant is placed in an electrolyte as the anode, and the thickness of the oxide layer on the implant surface is electrochemically increased from an average of 17-200nm to an average of 600-1000nm. At the same time, a microscopic multi-dimensional structure is formed, which jointly promotes the osteogenic properties of the implant surface. ③ Plasma spraying technology: This technology generally uses hydroxyapatite (HAP) or β-tricalcium phosphate (β-TCP) and other bone-like chemicals to be plasma-sprayed onto the surface of titanium implants. By leveraging the excellent biocompatibility, low immunogenicity, and corrosion resistance of HAP, the hydrophilicity and bone bonding ability of pure titanium implants can be improved. ④ UV activation: Pure titanium can form a TiO2 layer on its surface under air conditions, and ultraviolet irradiation can trigger a photocatalytic redox reaction on the TiO2 surface, forming active groups such as hydroxyl groups and oxygen free radicals with strong oxidizing ability, and decomposing surface organic matter to produce a super-hydrophilic surface. ⑤ Laser surface treatment technology: Femtosecond lasers can be used to prepare multi-level roughness on the surface of pure titanium implants that is conducive to cell attachment and growth, thereby improving the biocompatibility of the implant and promoting the adhesion and growth of osteoblasts on the implant surface. During the treatment process, the hydrophilicity of the titanium implant surface can be adjusted by controlling the laser energy density. However, the surface of super-hydrophilic implants produced using existing technologies is easily contaminated by carbon and nitrogen compounds in the air, causing them to quickly lose their super-hydrophilic properties. These implants must be stored in a special environment, such as immersion in a 0.9% sodium hydroxide solution. Alternatively, the implants must undergo chairside restoration (using sodium hydroxide solution or a specialized UV light device) before use to achieve super-hydrophilic activation. Furthermore, existing super-hydrophilic implants lack antibacterial properties, making post-implantation wounds susceptible to infection and hindering post-implantation oral care. Summary of the Invention

[0004] In order to overcome the problems existing in the prior art, one of the objectives of the present invention is to provide an implant.

[0005] A second object of the present invention is to provide a method for preparing the above-mentioned implant.

[0006] A third object of the present invention is to provide a dental implant.

[0007] A fourth object of the present invention is to provide an application of an implant in the preparation of medical implant materials.

[0008] In order to achieve the above object, the technical solution adopted by the present invention is:

[0009] The first aspect of the present invention provides an implant comprising a material body, a metal oxide layer, a mixed crystal layer and a CaP crystal layer arranged in sequence from the inside to the outside; the metal oxide layer comprises a metal oxide nanorod array; the metal oxide is selected from at least one of zinc oxide and silver oxide; the mixed crystal layer comprises CaP crystals and metal oxide crystals.

[0010] In the present invention, the metal oxide layer includes a metal oxide nanorod array structure. The metal oxide nanorods have a rough surface and a sharp shape, which can puncture or damage the cell membrane of the strain, thereby achieving physical sterilization. At the same time, the metal oxide nanorods will continuously release antibacterial metal ions during the hydrolysis process, thereby achieving chemical sterilization. The mixed crystal layer enhances the adhesion of the CaP crystal layer, thereby preventing the CaP crystal layer from falling off when the implant is in use. The CaP crystal layer can protect the metal oxide layer, thereby preventing the metal oxide layer from rapidly degrading during use, and can also give the implant a super hydrophilic surface.

[0011] Preferably, the implant is made of a superhydrophilic material. Further preferably, the water contact angle of the implant is ≤5°. Even more preferably, the implant is made of a superhydrophilic material with a water contact angle of 0° to 2°. The implant of the present invention has a water contact angle close to 0°, indicating excellent hydrophilicity.

[0012] Preferably, the water contact angle of the implant is less than 5° after being stored in air for 20 days.

[0013] Preferably, the content of the CaP crystals decreases gradually from the surface layer of the mixed crystal layer to the inner layer of the mixed crystal layer.

[0014] Preferably, the content of the metal oxide crystals increases gradually from the surface layer of the mixed crystal layer to the inner layer of the mixed crystal layer.

[0015] Preferably, the molar ratio of calcium to phosphorus in the mixed crystal layer is 10:(4-8); further preferably, the molar ratio of calcium to phosphorus in the mixed crystal layer is 10:(5-7).

[0016] Preferably, the thickness of the mixed crystal layer is 0.1 to 10 nm; more preferably, the thickness of the mixed crystal layer is 1 to 8 nm; even more preferably, the thickness of the mixed crystal layer is 2 to 5 nm.

[0017] Preferably, the thickness of the metal oxide layer is 200 to 2000 nm; further preferably, the thickness of the metal oxide layer is 500 to 1000 nm.

[0018] Preferably, the thickness of the CaP crystal layer is 3 to 100 nm, more preferably, the thickness of the CaP crystal layer is 5 to 50 nm, and even more preferably, the thickness of the CaP crystal layer is 10 to 20 nm.

[0019] Preferably, the diameter of the metal oxide nanorods is 50 to 200 nm; further preferably, the diameter of the metal oxide nanorods is 80 to 150 nm; even further preferably, the diameter of the metal oxide nanorods is 80 to 120 nm.

[0020] Preferably, the material body is titanium; further preferably, the material body is pure titanium or a titanium alloy.

[0021] Preferably, the material of the material body is selected from at least one of TA3 titanium, TA4 titanium, TA5 titanium, titanium aluminum vanadium alloy, titanium aluminum zirconium alloy, titanium niobium alloy, and nickel titanium alloy.

[0022] The second aspect of the present invention provides a method for preparing the implant provided in the first aspect of the present invention, comprising the following steps:

[0023] S1: pre-treating the surface of the material body, then coating the mixed metal source and stabilizer on the surface of the pre-treated material body, and then annealing to obtain the treated material body;

[0024] S2: subjecting the treated material body, hexamethylenetetramine / triammonium citrate, and a metal source to a hydrothermal reaction, followed by heat treatment to obtain a metal oxide layer;

[0025] S3: coating a mixture of a calcium source and a phosphorus source on the surface of the metal oxide layer, and performing annealing treatment to obtain the implant.

[0026] Preferably, the annealing temperature in step S1 is 450°C to 550°C; further preferably, the annealing temperature in step S1 is 480°C to 540°C; still further preferably, the annealing temperature in step S1 is 480°C to 520°C; more preferably, the annealing temperature in step S1 is 490°C to 510°C.

[0027] Preferably, the annealing treatment time in step S1 is 20 to 40 minutes; more preferably, the annealing treatment time in step S1 is 25 to 35 minutes.

[0028] Preferably, step S1 is: grinding and polishing the surface of the material body, then washing it with a detergent, mixing the metal source and the stabilizer and coating them on the surface of the pretreated material body, then drying it, repeating the coating and drying steps 0 to 5 times, and then annealing to obtain the treated material body.

[0029] Preferably, the drying temperature is 100-140°C; more preferably, the drying temperature is 110-130°C.

[0030] Preferably, in step S1, the concentration of the metal source is 0.02-0.1 mol / L.

[0031] Preferably, in step S1, the mass ratio of the metal source to the stabilizer is 1:(5-8).

[0032] Preferably, the concentration of the metal source in step S2 is 0.01 to 0.05 mol / L.

[0033] The concentration of the metal source in step S1 and step S2 needs to be within the above range, so that an excellent mixed crystal layer and CaP crystal layer can be obtained during preparation.

[0034] Preferably, in step S2, the mass ratio of the metal source to hexamethylenetetramine is 1:(0.8-1.2); further preferably, in step S2, the mass ratio of the metal source to hexamethylenetetramine is 1:(0.9-1.1).

[0035] Preferably, in step S2, the mass ratio of the metal source to triammonium citrate is 1:(0.8-1.2); further preferably, in step S2, the mass ratio of the metal source to triammonium citrate is 1:(0.9-1.1).

[0036] Preferably, the surface pretreatment step of the material body is: grinding and polishing the surface of the material body, and then cleaning it; further preferably, the surface pretreatment step of the material body is: grinding and polishing the surface of the material body, and then washing it with a detergent; the detergent includes at least one of acetone, ethanol, and deionized water; further preferably, the surface pretreatment step of the material body is: grinding and polishing the surface of the material body to above 2000 mesh, and then washing it with acetone, ethanol, and deionized water in sequence.

[0037] Preferably, the hydrothermal reaction temperature in step S2 is 90°C to 100°C; further preferably, the hydrothermal reaction temperature in step S2 is 92°C to 98°C; even further preferably, the hydrothermal reaction temperature in step S2 is 94°C to 96°C.

[0038] Preferably, the hydrothermal reaction time in step S2 is 1 h to 10 h; further preferably, the hydrothermal reaction time in step S2 is 2 h to 8 h; even further preferably, the hydrothermal reaction time in step S2 is 3 h to 7 h.

[0039] Preferably, the heat treatment temperature in step S2 is 300° C. to 400° C.; more preferably, the heat treatment temperature in step S2 is 320° C. to 380° C.; even more preferably, the heat treatment temperature in step S2 is 340° C. to 360° C. The heat treatment step is used to remove organic contaminants remaining on the surface.

[0040] Preferably, the heat treatment time in step S2 is 1 to 3 hours; further preferably, the heat treatment time in step S2 is 1.5 to 2.5 hours.

[0041] Preferably, the annealing temperature in step S3 is 500°C to 700°C; further preferably, the annealing temperature in step S3 is 550°C to 650°C; even further preferably, the annealing temperature in step S3 is 580°C to 620°C.

[0042] Preferably, the annealing time in step S3 is 30 min to 120 min; further preferably, the annealing time in step S3 is 40 min to 100 min; even further preferably, the annealing time in step S3 is 40 min to 80 min.

[0043] Preferably, in step S1, the coating step is: coating by spin coating; the number of spin coating times is 1 to 20 times; further preferably, in step S1, the coating step is: coating by spin coating; the number of spin coating times is 2 to 15 times; even further preferably, in step S1, the coating step is: coating by spin coating; the number of spin coating times is 3 to 10 times.

[0044] Preferably, in step S3, the coating step is performed by spin coating, and the number of spin coatings is 1 to 20 times. Further preferably, in step S3, the coating step is performed by spin coating, and the number of spin coatings is 2 to 15 times. Even more preferably, in step S3, the coating step is performed by spin coating, and the number of spin coatings is 3 to 10 times. The present invention adopts a method of multiple spin coating of a mixture of a calcium source and a phosphorus source. The mixture of the calcium source and the phosphorus source is coated on the surface of the metal oxide layer and penetrates into the interior of the metal oxide layer, forming CaP crystals and metal oxide crystals during annealing, and the content of the CaP crystals decreases from the surface of the mixed crystal layer to the inner layer of the mixed crystal layer, while the content of the metal oxide crystals increases from the surface of the mixed crystal layer to the inner layer of the mixed crystal layer.

[0045] Preferably, the calcium source is selected from at least one of calcium nitrate, calcium chloride, calcium chlorate, and calcium gluconate.

[0046] Preferably, the phosphorus source is selected from at least one of phosphorus pentoxide and phosphorus trioxide.

[0047] Preferably, the metal source is selected from at least one of a zinc source and a silver source.

[0048] Preferably, the zinc source is selected from at least one of zinc chloride, zinc acetate and zinc nitrate.

[0049] Preferably, the silver source is selected from at least one of silver nitrate and silver acetate.

[0050] Preferably, the stabilizer is selected from at least one of ethanolamine, diethanolamine and triethanolamine.

[0051] The third aspect of the present invention provides a dental implant, comprising the implant provided by the first aspect of the present invention.

[0052] The dental implant of the present invention has all the features and effects of the implant provided by the first aspect of the present invention.

[0053] The fourth aspect of the present invention provides use of the implant provided in the first aspect of the present invention in preparing a medical implant material.

[0054] Preferably, the medical implant material comprises a medical implant material for human body or a medical implant material for animal.

[0055] The present invention has the following beneficial effects: the implant of the present invention uses chemical sterilization through the antibacterial metal ions produced by the degradation of metal oxide nanorods, while also performing physical sterilization by puncturing the cell membranes of bacterial strains due to the rough, sharp surface morphology of the metal oxide nanorods. This can achieve good antibacterial effects against both Gram-positive and Gram-negative bacteria, alleviate post-implantation inflammatory reactions, reduce immune responses in the event of post-implantation infection, prevent infection, and shorten wound healing time. Furthermore, due to the coating effect of the mixed crystal layer on the metal oxide layer, the antibacterial metal ions are slowly released over a long period of time, achieving long-lasting antibacterial effects while also reducing post-implantation inflammatory reactions. In addition, on the one hand, the mixed crystal layer can give the implant surface long-lasting super-hydrophilic properties, which can promote the adsorption and coagulation of blood on the implant surface. The mixed crystal layer can slowly release calcium ions and phosphorus ions, promote the osteogenic differentiation of stem cells around the implant, and shorten the recovery time after implantation; on the other hand, it can reduce the degradation rate of metal oxide nanorods and improve storage stability, so that the implant still has excellent antibacterial, long-lasting anti-inflammatory and osteopromoting effects after being stored in an air environment for 20 days. It is particularly suitable for patients with high risk of infection and poor osteogenesis after implantation. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] FIG1 is a flow chart of the preparation process of the titanium implant containing ZnO nanorods in Example 1.

[0057] 2a-2b are scanning electron microscope images of the Ti material body and Ti-ZnO in Example 1.

[0058] 3a-3c are scanning electron micrographs of the super-hydrophilic implants in Examples 1-3.

[0059] FIG4 is a surface contact angle test diagram of the super-hydrophilic implant in Example 3.

[0060] 5a-5d are transmission electron micrographs of the super-hydrophilic implant in Example 3.

[0061] 6a-6l are scanning electron micrographs of the degradation process of Ti-ZnO in Example 1 and Ti-ZnO@CaP5 in Example 3.

[0062] Figures 7a-7f are antibacterial performance test diagrams of the Ti material body and Ti-ZnO in Example 1 and Ti-ZnO@CaP5 in Example 3.

[0063] 8a-8l are graphs showing the anti-inflammatory performance of the Ti material body and Ti-ZnO in Example 1, and Ti-ZnO@CaP5 in Example 3.

[0064] 9a-9b are test diagrams of the osteogenic performance of the Ti material body and Ti-ZnO in Example 1, and Ti-ZnO@CaP5 in Example 3. DETAILED DESCRIPTION

[0065] The specific implementation of the present invention will be further described in detail below in conjunction with the accompanying drawings and examples, but the implementation and protection of the present invention are not limited thereto. It should be noted that if there are any processes that are not particularly described in detail below, they can be implemented or understood by those skilled in the art with reference to the prior art. The reagents or instruments used that do not indicate the manufacturer are all conventional products that can be purchased commercially.

[0066] In some embodiments of the present invention, the present invention provides an implant comprising a material body, a metal oxide layer, a mixed crystal layer and a CaP crystal layer arranged in sequence from the inside to the outside; the metal oxide layer comprises a metal oxide nanorod array; the metal oxide is selected from at least one of zinc oxide and silver oxide; the mixed crystal layer comprises CaP crystals and metal oxide crystals.

[0067] In some embodiments of the present invention, the implant is a superhydrophilic material. In some embodiments of the present invention, the water contact angle of the implant is ≤5°. In some embodiments of the present invention, the implant is a superhydrophilic material with a water contact angle of 0° to 2°. In some embodiments of the present invention, the water contact angle of the implant is close to 0°, indicating excellent hydrophilicity.

[0068] In some embodiments of the present invention, the water contact angle of the implant is less than 5° after being stored in air for 20 days.

[0069] In some embodiments of the present invention, the content of CaP crystals decreases from the surface of the mixed crystal layer to the inner layer of the mixed crystal layer, and the content of metal oxide crystals increases from the surface of the mixed crystal layer to the inner layer of the mixed crystal layer.

[0070] In some embodiments of the present invention, the molar ratio of calcium to phosphorus in the mixed crystal layer is 10:(4-8); in some embodiments of the present invention, the molar ratio of calcium to phosphorus in the mixed crystal layer is 10:(5-7).

[0071] In some embodiments of the present invention, the thickness of the mixed crystal layer is 0.1 to 10 nm; in some embodiments of the present invention, the thickness of the mixed crystal layer is 1 to 8 nm; in some embodiments of the present invention, the thickness of the mixed crystal layer is 2 to 5 nm.

[0072] In some embodiments of the present invention, the thickness of the CaP crystal layer is 3 to 100 nm. In some embodiments of the present invention, the thickness of the CaP crystal layer is 5 to 50 nm. In some embodiments of the present invention, the thickness of the CaP crystal layer is 10 to 20 nm.

[0073] In some embodiments of the present invention, the thickness of the metal oxide layer is 200-2000 nm; in some embodiments, the thickness of the metal oxide layer is 500-1000 nm.

[0074] In some embodiments of the present invention, the diameter of the metal oxide nanorods is 50 to 200 nm; in some embodiments, the diameter of the metal oxide nanorods is 80 to 150 nm; in some embodiments, the diameter of the metal oxide nanorods is 80 to 120 nm.

[0075] In some embodiments of the present invention, the material body is a titanium material body; in some embodiments of the present invention, the material body is pure titanium or a titanium alloy.

[0076] In some embodiments of the present invention, the material of the material body is selected from at least one of TA3 titanium, TA4 titanium, TA5 titanium, titanium aluminum vanadium alloy, titanium aluminum zirconium alloy, titanium niobium alloy, and nickel titanium alloy.

[0077] In some embodiments of the present invention, the present invention further provides a method for preparing the above-mentioned implant, comprising the following steps:

[0078] S1: pre-treating the surface of the material body, then coating the mixed metal source and stabilizer on the surface of the pre-treated material body, and then annealing to obtain the treated material body;

[0079] S2: subjecting the treated material body, hexamethylenetetramine / triammonium citrate, and the metal source to a hydrothermal reaction, followed by heat treatment to obtain a metal oxide layer;

[0080] S3: coating a mixture of a calcium source and a phosphorus source on the surface of the metal oxide layer, and performing annealing treatment to obtain the implant.

[0081] In some embodiments of the present invention, the temperature of the annealing treatment in step S1 is 450°C to 550°C; in some embodiments of the present invention, the temperature of the annealing treatment in step S1 is 480°C to 540°C; in some embodiments of the present invention, the temperature of the annealing treatment in step S1 is 480°C to 520°C; in some embodiments of the present invention, the temperature of the annealing treatment in step S1 is 490°C to 510°C.

[0082] In some embodiments of the present invention, the annealing treatment time in step S1 is 20 to 40 minutes; in some embodiments of the present invention, the annealing treatment time in step S1 is 25 to 35 minutes.

[0083] In some embodiments of the present invention, step S1 is: grinding and polishing the surface of the material body, then washing it with a detergent, mixing the metal source and the stabilizer and coating them on the surface of the pretreated material body, then drying it, repeating the coating and drying steps 0 to 5 times, and then annealing to obtain the treated material body.

[0084] In some embodiments of the present invention, the drying temperature is 100-140°C; in some embodiments of the present invention, the drying temperature is 110-130°C.

[0085] In some embodiments of the present invention, in step S1, the concentration of the metal source is 0.02-0.1 mol / L.

[0086] In some embodiments of the present invention, in step S1, the mass ratio of the metal source to the stabilizer is: 1:(5-8).

[0087] In some embodiments of the present invention, in step S2, the mass ratio of the metal source to hexamethylenetetramine is 1:(0.8-1.2); in some embodiments, in step S2, the mass ratio of the metal source to hexamethylenetetramine is 1:(0.9-1.1).

[0088] In some embodiments of the present invention, in step S2, the mass ratio of the metal source to triammine citrate is 1:(0.8-1.2); in some embodiments, in step S2, the mass ratio of the metal source to triammine citrate is 1:(0.9-1.1).

[0089] In some embodiments of the present invention, the concentration of the metal source in step S2 is 0.01-0.05 mol / L.

[0090] In some embodiments of the present invention, the surface pretreatment step of the material body is: grinding and polishing the surface of the material body, and then cleaning it; in some embodiments of the present invention, the surface pretreatment step of the material body is: grinding and polishing the surface of the material body, and then washing it with a detergent; the detergent includes at least one of acetone, ethanol, and deionized water; in some embodiments of the present invention, the surface pretreatment step of the material body is: grinding and polishing the surface of the material body to above 2000 mesh, and then washing it with acetone, ethanol, and deionized water in sequence.

[0091] In some embodiments of the present invention, the hydrothermal reaction temperature in step S2 is 90°C to 100°C; in some embodiments of the present invention, the hydrothermal reaction temperature in step S2 is 92°C to 98°C; in some embodiments of the present invention, the hydrothermal reaction temperature in step S2 is 94°C to 96°C.

[0092] In some embodiments of the present invention, the hydrothermal reaction time in step S2 is 1 h to 10 h; in some embodiments of the present invention, the hydrothermal reaction time in step S2 is 2 h to 8 h; in some embodiments of the present invention, the hydrothermal reaction time in step S2 is 3 h to 7 h.

[0093] In some embodiments of the present invention, the heat treatment temperature in step S2 is 300° C. to 400° C.; in some embodiments of the present invention, the heat treatment temperature in step S2 is 320° C. to 380° C.; and in some embodiments of the present invention, the heat treatment temperature in step S2 is 340° C. to 360° C. The heat treatment step is used to remove organic contaminants remaining on the surface.

[0094] In some embodiments of the present invention, the heat treatment time in step S2 is 1 to 3 hours; in some embodiments of the present invention, the heat treatment time in step S2 is 1.5 to 2.5 hours.

[0095] In some embodiments of the present invention, the temperature of the annealing treatment in step S3 is 500-700°C; in some embodiments, the temperature of the annealing treatment in step S3 is 550-650°C; in some embodiments, the temperature of the annealing treatment in step S3 is 580-620°C.

[0096] In some embodiments of the present invention, the annealing treatment time in step S3 is 30 min to 120 min; in some embodiments of the present invention, the annealing treatment time in step S3 is 40 min to 100 min; in some embodiments of the present invention, the annealing treatment time in step S3 is 40 min to 80 min.

[0097] In some embodiments of the present invention, in step S1, the coating step is: coating by spin coating; the number of spin coating times is 1 to 20 times; in some embodiments, the number of spin coating times is 2 to 15 times; in some embodiments, the number of spin coating times is 3 to 10 times.

[0098] In some embodiments of the present invention, in step S3, the coating step is: coating by spin coating; the number of spin coating times is 1 to 20 times; in some embodiments, the number of spin coating times is 2 to 15 times; in some embodiments, the number of spin coating times is 3 to 10 times.

[0099] In some embodiments of the present invention, the calcium source is selected from at least one of calcium nitrate, calcium chloride, calcium chlorate, and calcium gluconate.

[0100] In some embodiments of the present invention, the phosphorus source is selected from at least one of phosphorus pentoxide and phosphorus trioxide.

[0101] In some embodiments of the present invention, the metal source is selected from at least one of a zinc source and a silver source. In some embodiments, the zinc source is selected from at least one of zinc acetate, zinc nitrate, and zinc chloride. In some embodiments, the silver source is selected from at least one of silver acetate and silver nitrate.

[0102] In some embodiments of the present invention, the stabilizer is selected from at least one of ethanolamine, diethanolamine, and triethanolamine.

[0103] In some embodiments of the present invention, the present invention further provides a dental implant, including the implant provided in the above embodiments.

[0104] In some embodiments of the present invention, the present invention further provides the use of the implant provided in the above embodiments in the preparation of medical implant materials for human body.

[0105] In some embodiments of the present invention, the present invention further provides the use of the implant provided in the above embodiments in preparing medical implant materials for animal bodies.

[0106] Example 1

[0107] The super-hydrophilic implant in this example is provided with a titanium implant body (i.e., a titanium material body), a zinc oxide layer, a mixed crystal layer, and a CaP crystal layer from the inside to the outside; the zinc oxide layer includes a zinc oxide nanorod array; the mixed crystal layer includes CaP crystals and metal oxide crystals.

[0108] Referring to the preparation flow chart in FIG1 , the super-hydrophilic implant in this example was prepared using the following preparation method, with the specific steps being:

[0109] (1) The titanium implant body was polished with 2000-grit sandpaper, and then ultrasonically cleaned with acetone, alcohol, and deionized water in sequence, and blown dry for later use. The cleaned sample was named Ti material body, denoted as Ti.

[0110] (2) Zinc acetate is used as a zinc source to prepare an ethanol solution with a zinc acetate concentration of 0.05 mol / L, and then the solution is fully stirred and mixed with a stabilizer ethanolamine at a mass ratio of 1:5 to obtain a mixed solution; the obtained mixed solution is spin-coated onto the surface of the pretreated Ti material body by a spin coating method (spin coating rate is 1000 rpm, spin coating time is 30 seconds), and then dried in a 120°C oven for 15 minutes, taken out, and then the above spin coating and drying steps are repeated in sequence, the number of repetitions is 2, and then annealed at 500°C for 30 minutes, as a seed layer for the generation of zinc oxide nanorods in the next step, recorded as the titanium material body containing the seed layer.

[0111] (3) preparing a mixed aqueous solution of zinc nitrate (at a concentration of 0.01 mol / L) and hexamethylenetetramine (denoted as a mixed aqueous solution, wherein the concentration ratio of zinc nitrate to hexamethylenetetramine is 1:1), placing the titanium material body containing the seed layer obtained in step (2) together with the mixed aqueous solution into a reactor and performing a hydrothermal reaction at 95° C. for 5 hours, wherein zinc oxide nanorods (ZnO nanorods) grow on the surface of the titanium material body containing the seed layer, and after ultrasonic cleaning, heat treatment at 350° C. for 2 hours to remove residual organic pollutants on the surface, thereby obtaining a titanium implant containing ZnO nanorods, denoted as Ti-ZnO;

[0112] (4) Calcium nitrate and phosphorus pentoxide were dissolved in ethanol to obtain a calcium nitrate original stock solution and a phosphorus pentoxide original stock solution with a concentration of 1 mol / L respectively; ethanol was then used as a diluent to adjust the calcium-phosphorus ratio to 10:6 to prepare a mixed reaction solution of calcium nitrate and phosphorus pentoxide as a calcium-phosphorus precursor solution; the prepared calcium-phosphorus precursor solution was spin-coated onto the titanium implant containing ZnO nanorods in Example 1, with the number of spin-coated layers being 1, and annealed at 600°C for 1 hour after the spin-coating to obtain the super-hydrophilic implant containing a calcium-phosphorus-zinc mixed crystal layer in this example, which was denoted as Ti-ZnO@CaP1. Wherein Ti-ZnO represents the inner layer, CaP1 represents the spin-coated layer or coating layer spin-coated on the Ti-ZnO surface, and @ represents spin-coating / coating.

[0113] The present invention adopts hydrothermal method to prepare zinc oxide nanorod array, and the specific reaction principle is: Zn(OH)2=Zn 2+ +2OH － (Dissolved) Zn 2+ +2OH － =ZnO+H2O(crystallization)

[0114] 1) In the first step of the reaction, ethanolamine does not directly participate in the reaction, but mainly plays the role of surfactant and stabilizer, helping and stabilizing the hydrolysis of zinc acetate and zinc acetate to generate Zn(OH)2, and the released Zn 2+ ZnO nuclei are generated on the surface of the titanium material. The presence of ZnO nuclei can guide the growth direction of subsequent nanorods and remove heavy metal ions that may interfere in the environment. The combined action of zinc source and ethanolamine is conducive to the subsequent growth of zinc oxide nanorods.

[0115] 2) In the second step of the reaction, zinc nitrate serves as the zinc source for the continued growth of nanorods, while cyclohexamethylenetetramine provides an alkaline environment and OH for the reaction. － source, and is beneficial to maintaining the growth of ZnO nanorods.

[0116] Example 2

[0117] The difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the number of spin-coated layers in step (4) of this example is 3 layers, denoted as Ti-ZnO@CaP3.

[0118] Example 3

[0119] The difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the number of spin-coated layers in step (4) of this example is 5, which is recorded as Ti-ZnO@CaP5.

[0120] Example 4

[0121] The difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the number of spin-coated layers in step (4) of this example is 10 layers, which is recorded as Ti-ZnO@CaP10.

[0122] Example 5

[0123] The preparation method of the super-hydrophilic implant in this example is different from that in Example 1 only in that triammonium citrate is used in this example instead of hexamethylenetetramine in Example 1.

[0124] Example 6

[0125] The only difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the hydrothermal temperature in step (3) in this example is 100° C. and the hydrothermal reaction time is 1 h.

[0126] Example 7

[0127] The only difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the hydrothermal temperature in step (3) in this example is 90° C. and the hydrothermal reaction time is 10 h.

[0128] Example 8

[0129] The difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the annealing time in step (4) of this example is 30 minutes.

[0130] Example 9

[0131] The difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that the annealing time in step (4) of this example is 2 hours.

[0132] The various properties of the super-hydrophilic implants prepared in Examples 5 to 9 are consistent with those of the super-hydrophilic implant in Example 1.

[0133] Example 10

[0134] The difference between the preparation method of the super-hydrophilic implant in this example and that in Example 1 is that silver nitrate is used instead of zinc acetate in step (2) and silver nitrate is used instead of zinc nitrate in step (3).

[0135] Performance testing:

[0136] (1) Surface morphology test

[0137] Scanning electron microscopy was used to examine the surface morphology of the Ti implant and the Ti-ZnO in Example 1. The specific test results are shown in Figure 2, where Figures 2a and 2b are SEM images of the Ti implant and the Ti-ZnO, respectively. Figure 2b shows that zinc oxide nanorod arrays with diameters of 50 to 70 nm were successfully formed on the surface of the Ti implant.

[0138] Scanning electron microscopy was used to test the surface morphology of the super-hydrophilic implants in Examples 1 to 3. The specific test results are shown in Figure 3, where Figures 3a, 3b, and 3c are SEM images of Ti-ZnO@CaP1 in Example 1, Ti-ZnO@CaP3 in Example 2, and Ti-ZnO@CaP5 in Example 3, respectively. Comparison of Figures 2b, 3a, 3b, and 3c shows that a calcium-phosphorus-zinc bone crystal layer is deposited on the surface of the zinc oxide nanorod arrays. The thickness of the calcium-phosphorus-zinc bone crystal layer deposited on the surface of the zinc oxide nanorod arrays increases with the number of spin-coated layers.

[0139] (2) Hydrophilicity test

[0140] The water contact angles of the super-hydrophilic implant surfaces of Examples 1 to 9 were measured using a contact angle tester. The specific testing method was as follows: 4 μL of ultrapure water was added to the sample surface via a syringe, and the static water contact angle (i.e., the initial contact angle) was measured. The initial contact angle test results for the super-hydrophilic implants of Examples 3 to 9 are shown in Table 1, and the surface contact angle test results for the Ti-ZnO@CaP5 of Example 3 are shown in Figure 4. As can be seen from Figure 4, the surface contact angle of the Ti-ZnO@CaP5 of Example 3 is close to 0°. The surface contact angles of the super-hydrophilic implants of Examples 1 to 9 of the present invention were all <10°, further demonstrating that the super-hydrophilic implants of the present invention have super-hydrophilic surfaces.

[0141] The super-hydrophilic implants in Examples 3 to 9 were placed in an air environment for 20 days, and then the water contact angles of the samples were tested according to the above test method. The test results are then recorded in Table 1 below.

[0142] Table 1. Contact angles of super-hydrophilic implants of Examples 3 to 9 of the present invention

[0143] The test results in Table 1 show that the super-hydrophilic implants in Examples 3-9 all had initial contact angles close to 0° at 0 days, and less than 5° after 20 days. This further demonstrates that the super-hydrophilic implants of the present invention can maintain super-hydrophilic properties (water contact angle less than 5°) in an air environment for a prolonged period (greater than 20 days). The super-hydrophilic implants in Examples 1-2 exhibit comparable hydrophilic properties to those in Examples 3-9.

[0144] (3) Transmission electron microscopy test

[0145] The super-hydrophilic Ti-ZnO@CaP5 in Example 3 was subjected to TEM detection, and the specific test results are shown in Figures 5a-5d, where Figure 5a is a TEM image of Ti-ZnO@CaP5, Figure 5b is a locally enlarged TEM image in the box of Figure 5a, Figure 5c is a test image of Figure 5b further enlarged to observe the mutual dissolution of the lattices in the mixed crystal layer, and Figure 5d is a SAED detection image of Ti-ZnO@CaP5. As shown in Figure 5a, the diameter of the ZnO nanorods containing the calcium-phosphorus-zinc mixed crystal layer in Ti-ZnO@CaP5 is about 100 nm, of which the thickness of the calcium-phosphorus-zinc mixed crystal layer is about 3 nm (see Figure 5b and Figure 5c for details), and gradually transitions from CaP to ZnO from the outside to the inside; the outermost layer of crystals is mainly hydroxyapatite crystals with typical (211) crystal planes and a crystal plane spacing of 0.27 nm; inside the interface, there is a typical ZnO crystal structure with a gradient interplanar spacing of 0.232 to 0.24 nm (see Figure 5c for details); the lattice compression near the interface is due to the defects introduced when calcium-phosphorus atoms diffuse into the ZnO lattice, and this conclusion is also confirmed by SAED detection (see Figure 5d for details).

[0146] (4) Degradation performance test

[0147] The degradation performance of Ti-ZnO in Example 1, Ti-ZnO@CaP1 in Example 1, Ti-ZnO@CaP3 in Example 2, and Ti-ZnO@CaP5 in Example 3 were tested respectively with the Ti implant body as a control. The specific test method was as follows: the test sample was immersed in a physiological buffered saline PBS solution, and then an electron microscope was used to observe whether the ZnO nanorods or ZnO nanorods containing a calcium phosphorus zinc mixed crystal layer on the surface of the super-hydrophilic implant collapsed after immersion for 1 day, 3 days, and 7 days. The results obtained using this test method are shown in Figures 6a-6l. Figures 6a, 6b, and 6c show SEM images of Ti-ZnO after immersion for 1, 3, and 7 days, respectively; Figures 6d, 6e, and 6f show SEM images of Ti-ZnO@CaP1 after immersion for 1, 3, and 7 days, respectively; Figures 6g, 6h, and 6i show SEM images of Ti-ZnO@CaP3 after immersion for 1, 3, and 7 days, respectively; and Figures 6j, 6k, and 6l show SEM images of Ti-ZnO@CaP5 after immersion for 1, 3, and 7 days, respectively. Figure 6a shows that CaP is not deposited on the surface of the ZnO nanorods in the Ti-ZnO. Degradation begins rapidly after 1 day of immersion, and by 3 days, most of the nanorod structures have collapsed (Figure 6c). Conversely, the degradation of ZnO nanorods after CaP deposition was delayed and the degradation rate was also slowed. Furthermore, the thicker the CaP layer, the later the degradation onset and the slower the degradation rate. After five CaP layers were deposited on the Ti-ZnO@CaP5 surface, the degradation time of ZnO nanorods containing a calcium-phosphorus-zinc mixed crystal layer was delayed compared to that of ZnO nanorods in Ti-ZnO, and the degradation rate was significantly lower, with the nanorod structure still retained on day 7.

[0148] (5) Antibacterial performance test

[0149] Taking the Ti material as a control, the antibacterial properties of Ti-ZnO in Example 1 and Ti-ZnO@CaP5 in Example 3 were tested respectively. The specific testing method was as follows: bacterial suspensions containing Escherichia coli (E.Coli) and Staphylococcus aureus (S.aureus) were co-incubated on the surfaces of different samples, and then the antibacterial efficiency was obtained by agar plate cloning experiment. The specific test results are shown in Figures 7a-7f, wherein Figures 7a, 7b and 7c are the antibacterial test diagrams of the Ti material body, Ti-ZnO and Ti-ZnO@CaP5 against Staphylococcus aureus, respectively; Figures 7d, 7e and 7f are the antibacterial test diagrams of the Ti material body, Ti-ZnO and Ti-ZnO@CaP5 against Escherichia coli, respectively. Figures 7a-7f show that compared to Ti-ZnO@CaP5, the Ti-ZnO sample has the highest surface antibacterial rate, with antibacterial rates exceeding 99% against both E. coli and S. aureus. Because the ZnO nanorods are coated with a calcium-phosphorus-zinc mixed crystal layer, which affects the release of zinc, the antibacterial rate of Ti-ZnO@CaP5 decreases. Furthermore, as the calcium-phosphorus-zinc mixed crystal layer thickens, the antibacterial rate of the super-hydrophilic implants gradually decreases. Overall, however, the super-hydrophilic implants of the present invention all exhibit antibacterial properties, with an antibacterial rate of at least 90%.

[0150] (6) Anti-inflammatory effect test

[0151] The anti-inflammatory effects of Ti-ZnO in Example 1 and Ti-ZnO@CaP5 in Example 3 were tested respectively, with the Ti implant as a control. The specific testing method was as follows: bacteria were first coated on the surface of the test sample, and then implanted into SD rats, with the Ti material as the control group. Tissue samples were taken 7 days and 14 days after implantation, and their in vivo antibacterial effects and the degree of inflammatory stress response were evaluated by Giemsa staining. The specific test results are shown in Figures 8a-8l, where Figures 8a, 8b, and 8c are anti-inflammatory effect test diagrams of the Ti material body, Ti-ZnO, and Ti-ZnO@CaP5 after 7 days of implantation, respectively; Figures 8d, 8e, and 8f are partial enlarged views of the inner parts of the boxes in Figures 8a, 8b, and 8c, respectively; Figures 8g, 8h, and 8i are anti-inflammatory effect test diagrams of the Ti material body, Ti-ZnO, and Ti-ZnO@CaP5 after 14 days of implantation, respectively; and Figures 8j, 8k, and 8l are partial enlarged views of the inner parts of the boxes in Figures 8g, 8h, and 8i, respectively. As shown in Figure 8, after the Ti material was implanted, the surrounding tissue showed severe inflammation after bacterial infection, which did not subside 14 days after implantation; while the surfaces of the Ti-ZnO and Ti-ZnO@CaP5 samples did not show strong acute or bacterial infection inflammation.

[0152] (7) Osteogenesis test

[0153] Using the Ti material as a control, the osteogenic effects of Ti-ZnO in Example 1 and Ti-ZnO@CaP5 in Example 3 were tested. The specific testing method was as follows: bone marrow mesenchymal stem cells (BMSCs) were seeded on the surface of each group of super-hydrophilic implants. The expression of alkaline phosphatase (ALP), a key factor in osteogenic differentiation, and the relative content of extracellular matrix mineralization were then measured after 3 and 7 days to evaluate the osteogenic performance of the different implants. The specific test results are shown in Figures 9a-9b, where Figure 9a shows the activity test of alkaline phosphatase and Figure 9b shows the relative quantitative results of extracellular matrix osteogenic mineralization. As shown in Figures 9a-9b, the osteogenic activity of Ti-ZnO is significantly lower than that of Ti-ZnO@CaP5 due to the degradation of ZnO nanorods and the release and accumulation of zinc ions on the surface. However, the protection of the CaP layer on the surface of Ti-ZnO@CaP5 reduces the degradation of ZnO nanorods and the release of Zn ions, which has a positive effect on promoting the osteogenic differentiation of BMSCs.

[0154] In summary, the implant of the present invention is sterilized by the antibacterial metal ions produced by the degradation of metal oxide nanorods, and has a good antibacterial effect on both Gram-positive and Gram-negative bacteria, can alleviate the inflammatory reaction after implantation, reduce the immune response in the case of infection after implantation, prevent infection, and shorten the wound healing time. In addition, due to the coating effect of the mixed crystal layer on the metal oxide layer, the antibacterial metal ions are slowly released, and the release time is long, which can achieve long-lasting antibacterial. In addition, the mixed crystal layer can give the implant surface a long-lasting super-hydrophilic property, which can promote the adsorption and coagulation of blood on the implant surface. The mixed crystal layer can slowly release calcium ions and phosphorus ions, promote the osteogenic differentiation of stem cells around the implant, and shorten the recovery time after the implant is implanted; on the other hand, the degradation rate of the metal oxide nanorods can be reduced, and the storage stability is high, so that the implant still has excellent antibacterial, long-lasting anti-inflammatory and osteopromoting effects after being stored in an air environment for 20 days, and is suitable for patients with high risk of infection and poor osteogenesis after implantation.

[0155] While the embodiments of the present invention have been described in detail above, the present invention is not limited to the embodiments described above. Various modifications may be made within the scope of knowledge possessed by a person skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof may be combined with one another unless there is a conflict.

Claims

1. An implant, characterized in that: It comprises a material body, a metal oxide layer, a mixed crystal layer and a CaP crystal layer arranged in sequence from the inside to the outside; the metal oxide layer comprises a metal oxide nanorod array; the metal oxide is selected from zinc oxide, silver oxide or a combination thereof; The mixed crystal layer includes CaP crystals and metal oxide crystals.

2. The implant according to claim 1, characterized in that: The implant is made of super hydrophilic material.

3. The implant according to claim 1, characterized in that: After the implant was stored in air for 20 days, the water contact angle was less than 5°.

4. The implant according to claim 1, characterized in that: The content of the CaP crystals decreases from the surface layer of the mixed crystal layer to the inner layer of the mixed crystal layer; the content of the metal oxide crystals increases from the surface layer of the mixed crystal layer to the inner layer of the mixed crystal layer.

5. The implant according to claim 1, characterized in that: The molar ratio of calcium to phosphorus in the mixed crystal layer is 10:(4-8).

6. The implant according to claim 1, characterized in that: The thickness of the mixed crystal layer is 0.1-10 nm.

7. The implant according to claim 1, characterized in that: The thickness of the metal oxide layer is 200-2000 nm.

8. The implant according to claim 1, characterized in that: The diameter of the metal oxide nanorods is 50-200 nm.

9. The implant according to claim 1, characterized in that: The material body is titanium.

10. The implant according to claim 9, characterized in that: The material body is selected from at least one of TA3 titanium, TA4 titanium, TA5 titanium, titanium aluminum vanadium alloy, titanium aluminum zirconium alloy, titanium niobium alloy, and nickel titanium alloy.

11. The method for preparing an implant according to any one of claims 1 to 10, characterized in that: The following steps are involved: S1: pre-treating the surface of the material body, then coating the mixed metal source and stabilizer on the surface of the pre-treated material body, and then annealing to obtain the treated material body; S2: subjecting the treated material body, hexamethylenetetramine / triammine citrate, and the metal source to a hydrothermal reaction, and then to a heat treatment to obtain a metal oxide layer; S3: coating a mixture of a calcium source and a phosphorus source on the surface of the metal oxide layer, and performing annealing treatment to obtain the implant.

12. The method for preparing an implant according to claim 11, characterized in that: The temperature of the annealing treatment in step S1 is 450° C. to 550° C., and the time of the annealing treatment is 20 to 40 minutes.

13. The method for preparing an implant according to claim 11, characterized in that: The material body surface pretreatment step is: grinding and polishing the material body surface, and then cleaning it.

14. The method for preparing an implant according to claim 11, characterized in that: The hydrothermal reaction temperature in step S2 is 90° C. to 100° C., and the hydrothermal reaction time is 1 h to 10 h.

15. The method for preparing an implant according to claim 11, characterized in that: The annealing temperature in step S3 is 500-700° C., and the annealing time is 30 min-120 min.

16. The method for preparing an implant according to claim 11, characterized in that: In the step S1 / S3, the coating step is: coating is performed by spin coating; the number of spin coating is 1 to 20 times.

17. The method for preparing an implant according to claim 11, characterized in that: The calcium source is selected from at least one of calcium nitrate, calcium chloride, calcium chlorate and calcium gluconate; And / or, the phosphorus source is selected from at least one of phosphorus pentoxide and phosphorus trioxide.

18. The method for preparing an implant according to claim 11, characterized in that: The metal source is selected from at least one of a zinc source and a silver source; And / or, the stabilizer is selected from at least one of ethanolamine, diethanolamine and triethanolamine.

19. A dental implant, characterized in that: The implant comprises the implant according to any one of claims 1 to 10.

20. Use of the implant according to any one of claims 1 to 10 in the preparation of medical implant materials.

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