CN113151828B - Biological coating with osteogenic and antibacterial functions on titanium alloy surface and preparation method and application thereof - Google Patents

Biological coating with osteogenic and antibacterial functions on titanium alloy surface and preparation method and application thereof Download PDF

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CN113151828B
CN113151828B CN202110244119.3A CN202110244119A CN113151828B CN 113151828 B CN113151828 B CN 113151828B CN 202110244119 A CN202110244119 A CN 202110244119A CN 113151828 B CN113151828 B CN 113151828B
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titanium alloy
biological coating
coating
titanium
titanium dioxide
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CN113151828A (en
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孙冬柏
俞宏英
司云辉
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Sun Yat Sen University
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Sun Yat Sen University
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    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C28/00—Coating for obtaining at least two superposed coatings either by methods not provided for in a single one of groups C23C2/00 - C23C26/00 or by combinations of methods provided for in subclasses C23C and C25C or C25D
    • C23C28/04—Coating for obtaining at least two superposed coatings either by methods not provided for in a single one of groups C23C2/00 - C23C26/00 or by combinations of methods provided for in subclasses C23C and C25C or C25D only coatings of inorganic non-metallic material
    • C23C28/042—Coating for obtaining at least two superposed coatings either by methods not provided for in a single one of groups C23C2/00 - C23C26/00 or by combinations of methods provided for in subclasses C23C and C25C or C25D only coatings of inorganic non-metallic material including a refractory ceramic layer, e.g. refractory metal oxides, ZrO2, rare earth oxides
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C22/00—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
    • C23C22/05—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using aqueous solutions
    • C23C22/60—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using aqueous solutions using alkaline aqueous solutions with pH greater than 8
    • C23C22/64—Treatment of refractory metals or alloys based thereon
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C22/00—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
    • C23C22/78—Pretreatment of the material to be coated
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C8/00—Solid state diffusion of only non-metal elements into metallic material surfaces; Chemical surface treatment of metallic material by reaction of the surface with a reactive gas, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
    • C23C8/06—Solid state diffusion of only non-metal elements into metallic material surfaces; Chemical surface treatment of metallic material by reaction of the surface with a reactive gas, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using gases
    • C23C8/08—Solid state diffusion of only non-metal elements into metallic material surfaces; Chemical surface treatment of metallic material by reaction of the surface with a reactive gas, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using gases only one element being applied
    • C23C8/10—Oxidising
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/08—Coatings comprising two or more layers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Abstract

The invention discloses a biological coating with osteogenesis and antibacterial functions on the surface of a titanium alloy, and a preparation method and application thereof. The preparation method of the biological coating comprises the following steps: carrying out oxidation treatment on the titanium alloy to form a porous titanium dioxide layer on the surface of the titanium alloy to obtain a sample 1; the sample 1 is immersed in a solution containing strontium ions, and subjected to hydrothermal reaction to form a biological coating. The biological coating has the multiple effects of strong binding force with a base material, promotion of cell adhesion, proliferation and osteogenic differentiation and antibiosis.

Description

Biological coating with osteogenic and antibacterial functions on titanium alloy surface and preparation method and application thereof
Technical Field
The invention relates to the technical field of surface modification of titanium alloy medical instruments, in particular to a biological coating with osteogenesis and antibacterial functions on the surface of a titanium alloy, and a preparation method and application thereof.
Background
The titanium alloy has the advantages of good ductility, formability, high elastic modulus, strong weight ratio and the like, and is a material very suitable for bearing a biological implant. In recent years, an (α + β) type Ti-6Al-4V (TC4) alloy has been further used in the field of artificial joints because it has higher strength and wear resistance than CP-titanium or other biocompatible titanium alloys. The elastic modulus of the TC4 alloy is low, close to that of bone, and due to a surface spontaneous passivation layer (TiO) 2 ) Has high electrochemical corrosion resistance in human body environment. TC4 titanium alloy benefits fromThe excellent mechanical property and excellent biocompatibility of the artificial implant are widely applied to the field of artificial implants.
However, the TC4 titanium alloy has many defects, which limits the further application of the alloy in clinical operation. Firstly, titanium alloy itself is a biologically inert material, and does not promote cell and tissue adhesion and is not sufficient to bond with human bone. The titanium implant is unstable and loosened in vivo, the implant is loosened to lack bone conduction and bone induction effects, and further, the bone tissue is difficult to generate good combination with a material interface. Secondly, Al element and V element in TC4 titanium alloy have adverse effect on human body. There are more and more reports that release of harmful metal ions in titanium alloys in vivo causes many problems and diseases, such as alzheimer's disease and tissue inflammation. Finally, titanium alloys themselves have no antimicrobial activity. Despite the continuous improvement of the sterilization and surgical procedures of bio-metal implants, microbial contamination is inevitable, especially in open bone trauma where the risk of wound infection is high. Titanium alloy implants are prone to carry bacteria from the surrounding environment during the implantation procedure, leading to serious clinical outcomes such as peri-implant inflammation, implant detachment, and even osteomyelitis and meningitis sepsis.
In order to solve the problems of biocompatibility and antibacterial performance of titanium alloy implants, extensive research on surface modification of titanium and titanium alloy has been conducted so far, and the research is mainly based on construction of bioactive coatings and addition of various antibacterial agents, including metal ions, nanoparticles or antibiotics. The related technology reports that a Hydroxyapatite (HA) coating can be prepared on the surface of a titanium alloy scaffold by a method of depositing poly-dopamine-assisted hydroxyapatite, cell experiment tests show that the HA coating enhances the adhesion, proliferation and osteogenic differentiation of osteoblasts in vitro, and in vivo experiments also show that the coating can effectively promote osseointegration and osteogenesis. However, the HA ceramic HAs poor mechanical properties, large brittleness and low strength, and the application of the HA ceramic to load parts is limited. In addition, the manganese-containing hydroxyapatite/titanium dioxide bioceramic coating is prepared on the surface of the titanium alloy by the related technology, and the composite coating has good bonding strength and structural stability, and simultaneously shows good biocompatibility and osteogenesis performance. However, the release of manganese doped in the coating and the dose-dependent cytotoxicity have not been effectively verified, and the coating lacks antibacterial properties.
In the related technology, TiAg alloy target is used as a source electrode, TiAg films with different Ag contents can be prepared on the surface of titanium alloy by magnetron sputtering, and then TiO loaded with Ag can be obtained by thermal oxidation treatment 2 A film. Ag doped TiO 2 The film improves the corrosion resistance of the titanium alloy and solves the problem that the titanium alloy is easy to cause bacterial infection in vivo when being used as an implant material. However, the noble metal is expensive, the cost of the adopted preparation process is high, the preparation process is not beneficial to actual production and application, and no osteoinductive property exists. In addition, a drug-loaded microsphere is prepared by compounding a gentamicin or rifampicin bone infection local common drug and gelatin, and is combined with the modified medical titanium alloy implant surface microporous layer, so that the controllable release of antibiotics can be realized. However, with the rapid development of multidrug resistance in pathogenic bacteria, antibiotics are no longer an effective method for preventing biofilm formation.
Therefore, in the prior art, the bonding performance of the coating and the matrix is insufficient, or the potential hazard of general cytotoxicity exists, and the coating cannot have osteogenesis and antibacterial performance at the same time. Specifically, the bone-like ceramic osteogenesis performance coating has larger difference with the microstructure of a matrix titanium alloy, the difference of the thermal expansion coefficients is obvious, abnormal stress is easily generated in the preparation process of a material coating, so that the bonding strength is not high, and the early falling is easily caused. The bacteriostatic properties of antibiotics or metal ion bacteriostatic agents depend on the release dose, and the release dose generally decreases with time, and a higher addition amount is generally selected to ensure sufficient bacteriostatic properties in the initial stage, but also leads to increased cytotoxicity.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. Therefore, the invention provides a biological coating with osteogenesis and antibacterial functions on the surface of the titanium alloy, and the biological coating has good cell adhesion, proliferation and osteogenesis differentiation performances and has light-operated antibacterial performance.
The invention also provides a preparation method and application of the biological coating.
Specifically, the invention adopts the following technical scheme:
the biological coating is positioned on the surface of an external titanium alloy and comprises a porous titanium dioxide layer combined with the surface of the titanium alloy, and strontium titanate nano-particles grow in situ on the surface of the porous titanium dioxide layer.
The biological coating according to the first aspect of the invention has at least the following beneficial effects:
in the biological coating, the porous titanium dioxide layer is firmly combined with the titanium alloy, so that the binding force of the biological coating and the base material is improved, the toxic elements Al and V on the surface of the titanium alloy are reduced, and the porous rough structure is also favorable for the adhesion and proliferation of stem cells. The strontium titanate nanoparticles can effectively promote osteogenic differentiation performance of stem cells on the surface of the coating, and a nano heterojunction interface formed by the strontium titanate nanoparticles and the porous titanium dioxide layer can provide higher bacteria inhibition efficiency under ultraviolet light. Namely, the biological coating has multiple effects of strong bonding force with a base material, promotion of cell adhesion, proliferation and osteogenic differentiation and antibiosis.
In some embodiments of the present invention, the thickness of the porous titanium dioxide layer is 20 to 25 μm.
In some embodiments of the present invention, the porous titanium dioxide layer is composed of titanium dioxide particles having a particle size of 2 to 3 μm.
In some embodiments of the present invention, the strontium titanate nanoparticles have a particle size of 200 to 300 nm.
The second aspect of the present invention provides a method for preparing a biological coating, comprising the following steps:
(1) carrying out oxidation treatment on the titanium alloy to form a porous titanium dioxide layer on the surface of the titanium alloy to obtain a sample 1;
(2) the sample 1 is immersed in a solution containing strontium ions, and subjected to hydrothermal reaction to form a biological coating.
The preparation method of the biological coating according to the second aspect of the invention has at least the following beneficial effects:
according to the invention, the porous titanium dioxide layer can be formed on the surface of the titanium alloy through an oxidation treatment process, the porous titanium dioxide layer not only forms a firm structure with the titanium alloy substrate, but also can reduce toxic elements Al and V on the surface of the titanium alloy, and the porous rough structure is also beneficial to adhesion and proliferation of stem cells. In the hydrothermal reaction, the porous titanium dioxide layer can be used as a precursor material and reacts with strontium ions to form strontium titanate nanoparticles in situ, so that the crystallinity of the strontium titanate nanoparticles is enhanced. The strontium titanate nanoparticles can effectively promote osteogenic differentiation performance of stem cells on the surface of the coating, and a nano heterojunction interface formed by the strontium titanate nanoparticles and the porous titanium dioxide layer can provide higher bacteria inhibition efficiency under ultraviolet light.
In some embodiments of the invention, the titanium alloy comprises any one or more of TC4, TC6, TA2, TA15, preferably TC 4.
In some embodiments of the present invention, in step (1), the oxidation treatment method is thermal oxidation. Porous rutile phase titanium dioxide can be formed on the surface of the titanium alloy by a thermal oxidation method.
In some embodiments of the present invention, the temperature of the thermal oxidation is 700 to 1200 ℃.
In some embodiments of the present invention, the temperature of the thermal oxidation is 800 to 1000 ℃.
In some embodiments of the present invention, the thermal oxidation time is 5 to 20 hours.
In some embodiments of the present invention, the thermal oxidation time is 8 to 12 hours.
In some embodiments of the present invention, the thermal oxidation process is: raising the temperature to 700-1200 ℃ at the speed of 3-10 ℃/min, then preserving the heat for 5-20 h, and then reducing the temperature at the speed of 3-10 ℃/min.
In some embodiments of the present invention, before the oxidizing treatment, the method further comprises the steps of polishing and cleaning the titanium alloy. The polishing method is only required to be capable of cleaning the surface of the titanium alloy, and the cleaning method is only required to be capable of removing impurities on the surface of the titanium alloy, and is not limited. By way of example, the steps of grinding and cleaning can be that the titanium alloy is ground to 2000# final surface finish step by using 240#, 400#, 600#, 800#, 1000#, 1500# and 2000# SiC sand papers respectively, and then ultrasonic cleaning is carried out in acetone, absolute ethyl alcohol and deionized water for 10-30 min in sequence.
In some embodiments of the present invention, in the step (2), the concentration of strontium ions in the solution containing strontium ions is 0.05-1 mol/L.
In some embodiments of the present invention, the concentration of strontium ions in the solution containing strontium ions is 0.05 to 0.15 mol/L.
In some embodiments of the present invention, the solution containing strontium ions is neutral and has a pH of 7.0 to 7.2.
In some embodiments of the invention, the strontium ion-containing solution comprises a strontium salt and a pH adjusting agent.
In some embodiments of the invention, the strontium salt comprises SrCl 2 、SrBr 2 、SrI 2 、SrCl 2 、Sr(NO 2 ) 2 、Sr(NO 3 ) 2 And hydrates thereof.
In some embodiments of the invention, the pH adjusting agent comprises any one or more of sodium hydroxide, potassium hydroxide, sodium citrate, ammonia.
In some embodiments of the present invention, the pH regulator is sodium hydroxide and/or an oxidizing agent, and the concentration of the pH regulator is 0.1 to 1 mol/L.
In some embodiments of the present invention, in the step (2), the temperature of the hydrothermal reaction is 150 to 300 ℃.
In some embodiments of the present invention, in the step (2), the temperature of the hydrothermal reaction is 4 to 10 hours.
In some embodiments of the present invention, after the hydrothermal reaction, a water soaking and washing step is further included. Specifically, after the hydrothermal reaction is finished, taking out a sample, soaking the sample in water for 10-36 hours, and changing water for multiple times in the soaking process; and after soaking, carrying out ultrasonic cleaning in water for 10-30 min, and then drying.
A third aspect of the present invention is to provide a titanium-based material comprising a titanium alloy having the above-described biological coating on the surface thereof.
The fourth aspect of the invention provides the use of the titanium-based material described above for the preparation of an orthopedic implant.
Compared with the prior art, the invention has the following beneficial effects:
the rutile phase porous titanium dioxide coating is grown on the surface of the titanium alloy in situ by a simple thermal oxidation process, forms firm combination with the substrate titanium alloy and reduces the content of Al and V elements on the surface of the titanium alloy; the porous rough surface is also beneficial to the adhesion and proliferation of stem cells. Meanwhile, the porous titanium dioxide coating can be used as a precursor material for preparing the strontium titanate nano particles, so that the crystallinity of the strontium titanate nano particles is enhanced. The strontium titanate nanoparticles grown in situ on the surface of the porous titanium dioxide coating by the hydrothermal method can effectively promote osteogenic differentiation performance of stem cells on the surface of the coating, and a nano heterojunction interface formed by the strontium titanate nanoparticles and the porous titanium dioxide layer can provide higher bacteria inhibition efficiency under ultraviolet light.
The preparation method provided by the invention is simple, short in period, low in cost and good in repeatability, and the coating material has good biocompatibility, is beneficial to enhancing osteoinduction and osseointegration of the titanium alloy artificial implant in clinical operation, and has light-operated antibacterial performance.
Drawings
FIG. 1 is an SEM image of the bio-coating of example 2;
FIG. 2 is an XRD spectrum of the bio-coating of example 2;
fig. 3 shows alizarin red S staining results for the bio-coatings of example 2(a) and comparative examples 1(b), 2(c), and 3 (d).
Detailed Description
The concept and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and those skilled in the art can obtain other embodiments without inventive effort based on the embodiments of the present invention, and all embodiments are within the protection scope of the present invention.
Example 1
The method for preparing the biological coating with osteogenesis and antibacterial functions on the surface of the TC4 titanium alloy comprises the following specific steps:
(1) pretreatment
A medical TC4 titanium alloy wafer (phi 16 multiplied by 2mm) is sequentially and gradually ground to 2000# final surface finish by using 240#, 400#, 600#, 800#, 1000#, 1500# and 2000# SiC sandpaper. And then ultrasonically cleaning the mixture in acetone, absolute ethyl alcohol and deionized water for 20min in sequence, taking out the mixture, and naturally drying the mixture in a fume hood.
(2) Thermal oxidation treatment
And (3) placing the polished and ultrasonically cleaned TC4 titanium alloy sample in the middle position in a tubular furnace in an air atmosphere, and performing high-temperature thermal oxidation treatment to obtain a porous titanium dioxide coating on the surface of the TC4 titanium alloy. The thermal oxidation treatment process comprises the following steps: the heating rate is 5 ℃/min, the heat preservation temperature is 900 ℃, the heat preservation time is 10h, and the cooling rate is 5 ℃/min.
(3) Preparation of hydrothermal reaction solution
Strontium salt SrCl 2 ·6H 2 Dissolving O and NaOH in deionized water, stirring uniformly for 3h, standing for clarification, and taking supernatant for later use. Wherein the SrCl in the mixed solution 2 ·6H 2 The concentration of O is 0.1mol/L, the concentration of NaOH is 0.5mol/L, and the solution is neutral. The reagents used in the experiment are all of analytical grade and do not need further purification.
4) Hydrothermal reaction
And (3) placing the TC4 titanium alloy sample with the porous titanium dioxide coating formed in the step (2) into a polytetrafluoroethylene inner container of a hydrothermal reaction kettle, adding the solution prepared in the step (3), immersing the TC4 titanium alloy, and sealing the hydrothermal reaction kettle. And (3) placing the hydrothermal reaction kettle in the middle position in an electrothermal blowing drying box, heating to 200 ℃ from room temperature, and keeping the temperature for 4 hours. After the reaction is finished, the hydrothermal reaction kettle is cooled to room temperature along with the furnace.
(5) Sample cleaning
And (5) soaking the sample obtained in the step (4) in deionized water for 24 hours, and replacing the deionized water for 3 times in the middle. Then ultrasonically cleaning in deionized water for 20min, and naturally drying in a fume hood to obtain the final sample.
Example 2
The present example is different from example 1 in that the hydrothermal reaction time of the present example is 6 hours. The other operations were the same as in example 1.
The surface SEM and XRD patterns of the final product obtained in this example are shown in fig. 1 and 2, respectively. As can be seen from FIG. 1, after the TC4 titanium alloy is subjected to thermal oxidation treatment and a strontium titanate coating is grown in situ, the surface is rough and is formed by irregular TiO with the size of 2-3 μm 2 The particles constitute the porous layer. In addition, in TiO 2 Strontium titanate nano-particle clusters are uniformly grown on the surfaces of the particles, the particle size of the strontium titanate nano-particles is 200-300 nm, and the strontium titanate nano-particles are unfolded in a petal shape, which shows that strontium titanate is successfully prepared on the surfaces of the oxide layers. In addition, TiO can be observed by SEM of the cross section of the product 2 The porous layer has a thickness of 20 to 25 μm.
FIG. 2 shows that TC4 titanium alloy is subjected to thermal oxidation treatment, and the phase of the titanium alloy is mainly rutile structure TiO 2 . SrTiO prepared on the basis of oxide layers 3 The crystallinity is better, and obvious SrTiO is detected at peak positions of 32.4 degrees, 39.8 degrees and the like 3 Diffraction peaks.
Example 3
The present example is different from example 1 in that the hydrothermal reaction time of the present example is 8 hours. The other operations were the same as in example 1.
Comparative example 1
A medical TC4 titanium alloy wafer (phi 16 multiplied by 2mm) is sequentially and gradually ground to 2000# final surface finish by using 240#, 400#, 600#, 800#, 1000#, 1500# and 2000# SiC sandpaper. And then ultrasonically cleaning the mixture in acetone, absolute ethyl alcohol and deionized water for 20min in sequence, taking out the mixture, and naturally drying the mixture in a fume hood.
Comparative example 2
This comparative example differs from example 2 in that no thermal oxidation treatment step was performed. That is, in this comparative example, the sample was pretreated and then directly subjected to hydrothermal reaction, and the specific pretreatment and hydrothermal reaction procedures were the same as in example 2.
Comparative example 3
This comparative example differs from example 1 in that no hydrothermal reaction step was carried out. The other operations were the same as in example 1.
And (3) performance detection:
the samples obtained in examples 1-3 and comparative examples 1-3 are used for carrying out cell proliferation experiments, osteogenic differentiation experiments and light-operated antibacterial experiments to test the biological properties, and the biological properties are as follows:
(1) cell proliferation assay
After autoclaving, samples of titanium alloy with a biocoating formed on the surface (Φ 16 × 2mm) were transferred to 24-well plates and three independent experiments were performed per set of examples (or comparative examples) to ensure accuracy. Will contain a density of 1X 10 4 1mL of MC3T3-E1 cell suspension per square centimeter was added to each pre-matrix-mounted well for 1, 3, and 5 days. At each time point, the matrix was transferred to a new plate well and washed slightly 3 times with PBS. After 1mL of fresh medium containing 5% (v/v) CCK-8 was added to each well, the cells were further cultured for 4 h. The Optical Density (OD) of 100. mu.L of suspension per well was measured using a microplate reader at a wavelength of 450 nm.
(2) Light-operated antibacterial experiment
After autoclaving, samples of titanium alloy with a biocoating formed on the surface (Φ 16 × 2mm) were transferred to 24-well plates and three independent experiments were performed per set of examples (or comparative examples) to ensure accuracy.
Escherichia coli (Escherichia coli) was used as the bacterium used for the test. Coli was added to 5mL of the nutrient broth, and cultured overnight at 37 ℃ to give a bacterial suspension, and the bacterial suspension concentration was adjusted to OD600 ═ 0.1. 1mL of E.coli suspension was added to each well of a 24-well plate and incubated overnight in a shaking incubator equipped with an ultraviolet lamp at a constant temperature (37 ℃). For each example (or comparative example), a dark light group was additionally set as a control. Specifically, the cells were completely wrapped with tinfoil and cultured overnight under the same conditions.
Immediately after the completion of the culture, OD values of the bacterial suspensions co-cultured with the samples of examples were measured at 600nm using a microplate reader, and then quantified.
The cell proliferation and photoactivated antibacterial activity test structures of the samples obtained in examples 1 to 3 and comparative examples 1 to 3 are shown in table 1 below.
TABLE 1 cell proliferation and Photocontrolled antibacterial Activity
Figure BDA0002963438610000081
The change rate of OD values of each example and comparative example compared to the TC4 titanium alloy without any treatment (comparative example 1) is shown in table 2 below:
TABLE 2 Rate of change of OD value for cell proliferation and photoactivated antibacterial activity (compare with comparative example 1)
Figure BDA0002963438610000082
The test result reflects that after the TC4 titanium alloy forms the biological coating, the proliferation activity of the diaphyseal cells on the surface of the TC4 titanium alloy can be effectively improved, and the optical-control antibacterial activity is obvious, and the antibacterial activity is also certain under the dark light condition. And the single coating of the dioxide layer (comparative example 3) and the single coating of the strontium titanate (comparative example 2) can not simultaneously obtain the double functions of osteogenesis and light-operated antibiosis.
(3) Osteogenic differentiation experiment
And (3) assessing mineralization of the extracellular matrix through alizarin red staining, and further evaluating osteogenic differentiation performance of cells on the surface of the titanium alloy sample containing the biological coating.
Specifically, after autoclaving, samples of titanium alloy (Φ 16 × 2mm) with a biocoating formed on the surface were transferred into 24-well plates. Osteogenic induction media containing 1mM dexamethasone, 50. mu.g/mL ascorbic acid, and 1M sodium β -glycerophosphate was prepared with α -MEM. To each well of a 24-well plate, 1mL of MC3T3-E1 cell suspension was added at a concentration of 2X 10 4 Individual cells/well. Osteogenic medium was changed 24 hours after induction. Osteogenic inductionAfter 14, 21d incubation, fixation with 4% paraformaldehyde for 30min at room temperature followed by 2 washes with PBS. Mu.l of 0.2% alizarin red S solution (pH 8.3) was added to each well. The staining was kept at room temperature for 30 min. After washing with water for 2 times, the surface of the sample was observed under an optical microscope for staining, and the results are shown in FIG. 3.
Fig. 3(a) is the result of alizarin red S staining of example 2, and it can be observed that there is uniform generation of red mineralized calcium nodules on the whole coating, which demonstrates that osteoblasts have good osteogenic differentiation performance on the composite coating. In contrast, in fig. 3 (b-d), no large area red calcium deposit was observed in the dyeing results of comparative examples 1-3, and partial calcium deposit was observed at the edge in comparative example 2, indicating that the osteogenic performance of the single coating was weaker than that of the composite coating.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such modifications are intended to be included in the scope of the present invention.

Claims (7)

1. A biological coating, characterized by: the biological coating is positioned on the surface of an external titanium alloy and comprises a porous titanium dioxide layer combined with the surface of the external titanium alloy, and strontium titanate nano-particles grow in situ on the surface of the porous titanium dioxide layer;
the porous titanium dioxide layer is composed of titanium dioxide particles, and the particle size of the titanium dioxide particles is 2-3 mu m;
the preparation method of the biological coating comprises the following steps:
(1) carrying out oxidation treatment on the titanium alloy to form a porous titanium dioxide layer on the surface of the titanium alloy to obtain a sample 1;
(2) dipping the sample 1 in a solution containing strontium ions, and carrying out hydrothermal reaction to form a biological coating;
in the step (1), the oxidation treatment method is thermal oxidation; the temperature of the thermal oxidation is 700-1200 ℃; the thermal oxidation time is 5-20 h.
2. The biological coating of claim 1, wherein: the thickness of the porous titanium dioxide layer is 20-25 mu m.
3. The biological coating according to claim 1 or 2, characterized in that: the particle size of the strontium titanate nanoparticles is 200-300 nm.
4. A method for preparing a bio-coating according to any one of claims 1 to 3, characterized in that: the method comprises the following steps:
(1) carrying out oxidation treatment on the titanium alloy to form a porous titanium dioxide layer on the surface of the titanium alloy to obtain a sample 1;
(2) dipping the sample 1 in a solution containing strontium ions, and carrying out hydrothermal reaction to form a biological coating;
in the step (1), the oxidation treatment method is thermal oxidation; the temperature of the thermal oxidation is 700-1200 ℃; the thermal oxidation time is 5-20 h.
5. The method according to claim 4, wherein: in the step (2), the temperature of the hydrothermal reaction is 150-300 ℃.
6. A titanium-based material characterized by: the titanium-based material comprises a titanium alloy, and the surface of the titanium alloy is provided with the biological coating of any one of claims 1-3.
7. Use of the titanium-based material according to claim 6 for the preparation of an orthopedic implant.
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