A medical titanium-based metal functional coating and preparation method thereof

Abstract

The present invention discloses a medical titanium-based metal functional coating and a preparation method thereof. The preparation method comprises the following steps: subjecting a pretreated titanium-based metal substrate A to an alkali heat treatment, washing with water, and drying to obtain a hydroxylated substrate B; subjecting substrate B to ion exchange, and then washing with water and drying to obtain substrate C; dissolving magnesium nitrate and silver nitrate as metal salts and 2,5-dihydroxyterephthalic acid as an organic ligand in a solvent, mixing them uniformly to obtain a precursor solution, immersing substrate C in the precursor solution for a hydrothermal reaction, and cooling to obtain substrate D; replacing excess organic ligands in substrate D, and drying to obtain a medical titanium-based metal functional coating. The medical titanium-based metal functional coating prepared by the present invention has good antibacterial properties and corrosion resistance, and good biocompatibility.

Description

Technical Field

[0001] The present invention relates to the technical field of medical biomaterial preparation, and in particular to a medical titanium-based metal functional coating and a preparation method thereof. Background Art

[0002] Due to their excellent mechanical properties and machinability, metal materials are widely used as biomedical implants in fields such as orthopedics, dentistry, and cardiovascular therapy. Titanium and its alloys, with their low density, high specific strength, good bio- and mechanical compatibility, and easy processing and molding, have become a high-volume, widely used, mid-range, and high-end surgical implant material. Despite this, titanium and its alloys still face numerous challenges during long-term surgical implantation, with bacterial infection being a major concern. Implants are sensitive to bacterial adhesion; the presence of approximately 100 bacteria per gram of tissue can trigger an infection. These bacteria adhere to the implant surface and rapidly proliferate, forming a dense biofilm. If a biofilm forms on the implant surface, the bacteria can hinder osseointegration, accelerate corrosion, and significantly damage adjacent tissues, leading to implant loosening, dislodgement, and even dislocation. Furthermore, numerous studies have shown that infection can stimulate the human immune system and trigger an inflammatory response, significantly shortening the effective lifespan of implants. Therefore, surface modification technologies that simultaneously enhance antimicrobial properties, biocompatibility, and corrosion resistance are essential.

[0003] In order to avoid the above problems, the surface modification of titanium and titanium alloys has been widely studied. Among them, constructing an antibacterial functional interface on the surface of the base metal is one of the common methods, which is mainly divided into three categories: antibacterial coating, anti-adhesion coating and anti-fouling release coating. At present, many titanium implant devices on the market use antibacterial coating methods and have successfully loaded antibiotics or antimicrobial peptides on the surface for antibacterial applications. However, bacterial resistance or complex production processes limit their further application. In order to circumvent this problem, metal ion Ag + 、Cu 2+ and Zn 2+ Commonly used to modify titanium surfaces, the release of antimicrobial ions can effectively mitigate antibiotic resistance. However, due to the sustained release of metal ions, metal ion-loaded implants, while capable of achieving a sustained antimicrobial effect, exhibit weak antimicrobial activity in the early stages of implantation, making them less effective in combating bacterial infections in the postoperative period. Summary of the Invention

[0004] The purpose of the present invention is to provide a medical titanium-based metal functional coating and a preparation method thereof, wherein the medical titanium-based metal functional coating has good antibacterial and corrosion resistance properties, and has good biocompatibility, and the preparation method thereof is simple and easy to operate.

[0005] The present invention is achieved in that:

[0006] In a first aspect, the present invention provides a method for preparing a medical titanium-based metal functional coating, comprising the following steps:

[0007] The pretreated titanium-based metal substrate A is subjected to an alkali heat treatment, washed with water, and dried to obtain a hydroxylated substrate B;

[0008] Substrate B is subjected to ion exchange, and then washed and dried to obtain substrate C;

[0009] Magnesium nitrate and silver nitrate are used as metal salts, and 2,5-dihydroxyterephthalic acid is used as an organic ligand, which are dissolved in a solvent and mixed evenly to obtain a precursor solution. Substrate C is immersed in the precursor solution to undergo a hydrothermal reaction, and substrate D is obtained after cooling.

[0010] The excess organic ligands in the substrate D are replaced, and after drying, a medical titanium-based metal functional coating is obtained.

[0011] Compared with the existing technology, the preparation method of the present invention is simple and easy to operate. The prepared medical titanium-based metal functional coating has good antibacterial and corrosion resistance, good biocompatibility when used as an implant, and wide applicability.

[0012] In an optional embodiment, the solvent is a mixture solvent consisting of N,N-dimethylformamide, anhydrous ethanol and deionized water.

[0013] In an optional embodiment, in the precursor solution, the mass volume ratio of the magnesium nitrate to the mixture solvent is (550-720) mg:(40-60) mL; the mass volume ratio of the silver nitrate to the mixture solvent is (5-15) mg:(40-60) mL; and the mass volume ratio of the 2,5-dihydroxyterephthalic acid to the mixture solvent is (140-180) mg:(30-60) mL.

[0014] In an optional embodiment, in the mixture solvent, the volume fraction ratio is N,N-dimethylformamide:anhydrous ethanol:deionized water=(30-45):(1-9):(1-6).

[0015] In an optional embodiment, the hydrothermal reaction temperature is 110-140° C., and the holding time is 18-36 hours.

[0016] In an optional embodiment, the precursor solution is uniformly mixed by ultrasonic stirring, the ultrasonic temperature is 25 to 35° C., and the time is 30 to 90 minutes.

[0017] In an optional embodiment, the alkali heat treatment is to immerse the pretreated titanium-based metal substrate A in a sodium hydroxide solution with a concentration of 3 to 8 mol / L, and perform alkali heat treatment at 60 to 90° C. for 18 to 36 hours.

[0018] In an optional embodiment, the ion exchange is performed by immersing the substrate B in a hydrochloric acid solution and a magnesium nitrate solution in sequence to perform ion exchange, thereby forming a magnesium titanate pre-coating on the surface of the substrate B.

[0019] In an optional embodiment, in the ion exchange step, the concentration of the hydrochloric acid solution is 0.05 to 0.1 mol / L; the concentration of the magnesium nitrate solution is 0.05 to 0.1 mol / L.

[0020] In an optional embodiment, in the ion exchange step, the soaking time in the hydrochloric acid solution is 30 to 60 minutes.

[0021] In an optional embodiment, in the ion exchange step, the soaking time in the magnesium nitrate solution is 30 to 60 minutes.

[0022] In an optional embodiment, in the ion exchange step, the water washing time is 5 to 10 minutes.

[0023] In an optional embodiment, in the ion exchange step, the drying temperature is 60-80° C. and the drying time is 1-3 hours.

[0024] In an optional embodiment, the method for replacing the excess organic ligands in the substrate D is: immersing the substrate D in N,N-dimethylformamide and methanol respectively.

[0025] In an optional embodiment, the substrate D is immersed in the N,N-dimethylformamide solution for 10 to 30 minutes; and immersed in the methanol solution for 1 to 3 hours.

[0026] In an optional embodiment, the drying method is vacuum drying, the vacuum drying temperature is 80-100° C., and the time is 2-4 hours.

[0027] In an optional embodiment, the pretreatment includes the following steps: polishing the titanium-based metal with sandpaper and then washing it with water, then ultrasonically cleaning it with acetone, anhydrous ethanol and deionized water in sequence, and drying it to obtain a pretreated titanium-based metal substrate A.

[0028] In an optional embodiment, in the pretreatment step, the sandpaper polishing is to polish the titanium-based metal using waterproof silicon carbide sandpaper with mesh sizes of 200, 600, 1000, 1500 and 2000 in sequence.

[0029] In an optional embodiment, the water washing in the pretreatment is rinsing with deionized water for 1 to 5 minutes.

[0030] In an optional embodiment, the acetone ultrasonic cleaning time is 10 to 20 minutes and the frequency is 20 to 50 kHz.

[0031] In an optional embodiment, the deionized water ultrasonic cleaning time is 10 to 20 minutes, and the frequency is 20 to 50 kHz.

[0032] In an optional embodiment, the drying temperature is 60-80° C., and the drying time is 1-3 hours.

[0033] In a second aspect, the present invention also provides a medical titanium-based metal functional coating prepared by any of the above-mentioned preparation methods.

[0034] The present invention has the following beneficial effects:

[0035] (1) The present invention can give medical titanium-based metals good antibacterial properties. By constructing a bacterial acid-responsive Mg / Ag-MOF74 coating on the surface of the titanium-based metal, Ag with significant bactericidal effects can be released in the early postoperative period. + Kill pathogens, and the constructed MOFs layer is Mg 2+ It is mainly cytotoxic.

[0036] (2) The coating of the present invention also provides a physical barrier layer with good biocompatibility, thereby achieving the effect of preventing corrosion. As a physical barrier layer, the MOF coating has the characteristics of good crystal symbiosis, dense structure, and effective repulsion of corrosive ions, thereby enhancing the corrosion resistance of the implant.

[0037] (3) The preparation process of the medical titanium-based metal functional coating of the present invention is simple and easy to operate, and has good prospects for large-scale application. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0039] Figure 1 Surface scanning electron micrographs of the samples prepared in Examples 1 to 3;

[0040] Figure 2 1 is the EDS graph of the samples prepared in Examples 1 to 3;

[0041] Figure 3 X-ray diffraction patterns of samples before and after functional membrane modification in Examples 1 to 3;

[0042] Figure 4 Schematic diagram of the water contact angle of the samples before and after the functional membrane modification of Examples 1 to 3;

[0043] Figure 5 The potentiodynamic polarization curves of the samples before and after functional membrane modification in Examples 1, 4 to 6 in simulated body fluids are shown;

[0044] Figure 6 Schematic diagram of the results of the plate viable bacteria counting method of the samples before and after functional membrane modification in Examples 1 to 3. DETAILED DESCRIPTION

[0045] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0046] The following is a detailed description of the medical titanium-based metal functional coating and its preparation method provided in this application.

[0047] Metal-organic frameworks (MOFs) have attracted considerable attention due to their high surface area, high porosity, and easily functionalized pore walls. They are widely used in adsorption, separation, catalysis, and biomedicine. With the deepening of research, MOFs have been found to have applications in antibacterial, antifungal, antiviral, and antiparasitic applications. In terms of antibacterial properties, MOFs can serve as excellent metal ion reservoirs and releasers, achieving, to a certain extent, environmentally responsive release of metal ions through the combination of organic ligands and metal ions. Therefore, the development of medical titanium-based metal MOF antibacterial functional coating materials holds great promise in the biomedical field.

[0048] This application proposes a method for preparing a medical titanium-based metal functional coating, comprising the following steps:

[0049] The pretreated titanium-based metal substrate A is subjected to an alkali heat treatment, washed with water, and dried to obtain a hydroxylated substrate B;

[0050] Substrate B is subjected to ion exchange, and then washed and dried to obtain substrate C;

[0051] Magnesium nitrate and silver nitrate are used as metal salts, and 2,5-dihydroxyterephthalic acid is used as an organic ligand, which are dissolved in a solvent and mixed evenly to obtain a precursor solution. Substrate C is immersed in the precursor solution to undergo a hydrothermal reaction, and substrate D is obtained after cooling.

[0052] The excess organic ligands in the substrate D are replaced, and after drying, a medical titanium-based metal functional coating is obtained.

[0053] For reference, the precursor solution contains a mixture of N,N-dimethylformamide, anhydrous ethanol, and deionized water. N,N-dimethylformamide is a good solvent for 2,5-dihydroxyterephthalic acid, promoting rapid crystal growth. The addition of anhydrous ethanol helps reduce the pore size of the subsequently formed MOFs. Deionized water can induce crystal growth along specific directions and increase crystal size. The interaction of these three solvents not only transforms the resulting coating's stripe structure into a more compact spherical structure but also induces the growth of its layered structure in different directions.

[0054] For reference, in the precursor solution, the mass volume ratio of magnesium nitrate to the mixture solvent is (550-720) mg:(40-60) mL, and illustratively it can be 550 mg:40 mL, 600 mg:40 mL, 640 mg:40 mL, 680 mg:40 mL, 720 mg:40 mL, 550 mg:50 mL, 600 mg:50 mL, 640 mg:50 mL, 680 mg:50 mL, 720 mg:50 mL, 550 mg:60 mL, 600 mg:60 mL, 640 mg:60 mL, 680 mg:60 mL, 720 mg:60 mL, etc., and it can also be any other value within the range of (550-720) mg:(40-60) mL, preferably 640 mg:50 mL. The mass volume ratio of silver nitrate to the mixture solvent is (5-15) mg:(40-60) mL, and illustratively can be 5 mg:40 mL, 8 mg:40 mL, 10 mg:40 mL, 12 mg:40 mL, 15 mg:40 mL, 5 mg:50 mL, 8 mg:50 mL, 10 mg:50 mL, 12 mg:50 mL, 15 mg:50 mL, 5 mg:60 mL, 8 mg:60 mL, 10 mg:60 mL, 12 mg:60 mL, 15 mg:60 mL, etc., and can also be any other value within the range of (5-15) mg:(40-60) mL; preferably, it can be 8 mg:50 mL. The mass volume ratio of 2,5-dihydroxyterephthalic acid and the mixed solvent is (140-180) mg: (30-60) mL, and can be 140 mg: 30 mL, 150 mg: 30 mL, 160 mg: 30 mL, 170 mg: 30 mL, 180 mg: 30 mL, 140 mg: 40 mL, 150 mg: 40 mL, 160 mg: 40 mL, 170 mg: 40 mL, 180 mg: 40 mL L, 140mg:50mL, 150mg:50mL, 160mg:50mL, 170mg:50mL, 180mg:50mL, 140mg:60mL, 150mg:60mL, 160mg:60mL, 170mg:60mL, 180mg:60mL, etc., and can also be any other value within the range of (140-180)mg:(30-60)mL; preferably 160mg:50mL.

[0055] For reference, in the mixture solvent, the volume fraction ratio is N,N-dimethylformamide:anhydrous ethanol:deionized water = (30-45):(1-9):(1-6), which can be illustratively 30:1:1, 32:1:1, 34:1:1, 36:1:1, 38:1:1, 40:1:1, 45:1:1, 30:6:4, 32:6:2, 34:4:2, 30:9:6, 45:9:6, 45:9:2, etc., or any other value within the range of (30-45):(1-9):(1-6). Preferably, the volume fraction ratio is N,N-dimethylformamide:anhydrous ethanol:deionized water = 15:3:2.

[0056] For reference, the hydrothermal reaction temperature is 110-140°C, and the holding time is 18-36h. Preferably, the hydrothermal reaction is carried out in a high-pressure reactor. First, the precursor solution is poured into the lining of the high-pressure reactor, and then the substrate C coating surface is placed into the lining of the reactor, the reactor is tightened, and finally the reactor is placed at a set temperature for hydrothermal reaction. It can be placed in a constant temperature blast drying oven, or a reactor with a heating module can be used. After completion, the sample is taken out after cooling to obtain substrate D. The hydrothermal reaction temperature can be illustratively 110°C, 120°C, 125°C, 130°C, 140°C, etc., or any other value within the range of 110-140°C. The holding time of the hydrothermal reaction can be illustratively 18h, 20h, 24h, 30h, 36h, etc., or any other value within the range of 18-36h. Preferably, the hydrothermal reaction is kept at 125°C for 24h.

[0057] For reference, the precursor solution is uniformly mixed by ultrasonic stirring, and the ultrasonic temperature is 25-35°C and the time is 30-90 minutes. The ultrasonic temperature can be 25°C, 30°C, 35°C or any other value within the range of 25-35°C, and the ultrasonic stirring time can be 30 minutes, 45 minutes, 60 minutes, 80 minutes, 90 minutes or any other value within the range of 30-90 minutes. Preferably, ultrasonic stirring is performed at 25°C for 60 minutes.

[0058] For reference, the alkali heat treatment is to immerse the pretreated titanium-based metal substrate A in a sodium hydroxide solution with a concentration of 3 to 8 mol / L and perform the alkali heat treatment at 60 to 90°C for 18 to 36 hours. The concentration of the sodium hydroxide solution can be 3 mol / L, 5 mol / L, 8 mol / L, or any other value within the range of 3 to 8 mol / L; the alkali heat treatment temperature can be 60°C, 70°C, 80°C, 90°C, or any other value within the range of 60 to 90°C; and the alkali heat treatment time can be 18 hours, 24 hours, 36 hours, or any other value within the range of 18 to 36 hours. Preferably, the NaOH solution concentration is 5 mol / L, and the alkali heat treatment is performed at 60°C for 24 hours.

[0059] For reference, the alkali heat treatment has a water washing time of 5 to 10 minutes, preferably 5 minutes, a drying temperature of 60 to 80° C., and a drying time of 1 to 3 hours, preferably 2 hours at 60° C.

[0060] For reference, the ion exchange step involves sequentially immersing substrate B in a hydrochloric acid solution and a magnesium nitrate solution to perform ion exchange, thereby forming a magnesium titanate pre-coating on the surface of substrate B. The ion exchange step aims to exchange sodium ions with magnesium ions, thereby forming a magnesium titanate pre-coating on the substrate surface, which facilitates the subsequent bonding of the MOFs coating to the substrate surface. In other embodiments, the hydrochloric acid solution can be replaced with a sulfuric acid solution, a nitric acid solution, or the like, to achieve the desired pickling effect.

[0061] For reference, in the ion exchange step, the concentration of the hydrochloric acid solution is 0.05-0.1 mol / L, and the immersion time is 30-60 min; the concentration of the magnesium nitrate solution is 0.05-0.1 mol / L, and the immersion time is 30-60 min. Preferably, the concentration of the HCl solution is 0.1 mol / L, and the immersion time is 60 min; the concentration of the Mg(NO3)2·6H2O solution is 0.1 mol / L, and the immersion time is 60 min.

[0062] For reference, in the ion exchange step, the water washing time is 5 to 10 minutes, preferably 5 minutes.

[0063] For reference, in the ion exchange step, the drying temperature is 60-80° C. and the drying time is 1-3 hours. Preferably, the drying is performed at 60° C. for 2 hours.

[0064] For reference, excess organic ligands in substrate D can be displaced by immersing the substrate in both an N,N-dimethylformamide solution and a methanol solution. Soaking substrate D in the N,N-dimethylformamide solution dissolves excess ligands without doping with impurities, ensuring sample purity and making the resulting coating more uniform. Soaking in methanol, on the other hand, displaces the N,N-dimethylformamide in the coating pores. Furthermore, methanol does not participate in the coordination reaction and enter the MOF lattice. It can be subsequently removed by drying, without adversely affecting the sample or the resulting coating.

[0065] For reference, the substrate D can be immersed in the N,N-dimethylformamide solution for 10 to 30 minutes, and immersed in the methanol solution for 1 to 3 hours. The immersion time of the substrate D in the N,N-dimethylformamide solution can be, for example, 10 minutes, 20 minutes, 30 minutes, or any other value within this range; preferably, 20 minutes. The immersion time of the substrate D in the methanol solution can be 1 hour, 2 hours, 3 hours, or any other value within this range; preferably, 2 hours.

[0066] For reference, the drying method is preferably vacuum drying, with a drying temperature of 80-100°C and a drying time of 2-4 hours. The vacuum drying temperature can illustratively be 80°C, 90°C, 100°C, or any other value within the range of 80-100°C; the drying time can be 2 hours, 3 hours, 4 hours, or any other value within the range of 2-4 hours. Preferably, vacuum drying is performed at 100°C for 3 hours.

[0067] For reference, the pretreatment includes the following steps: polishing the titanium-based metal with sandpaper and then washing it with water, then ultrasonically cleaning it with acetone, anhydrous ethanol and deionized water in sequence, and obtaining the pretreated titanium-based metal substrate A after drying.

[0068] Preferably, in the pretreatment step, the sandpaper polishing is to polish the titanium-based metal using waterproof silicon carbide sandpaper with mesh sizes of 200, 600, 1000, 1500 and 2000 in sequence.

[0069] For reference, in the pretreatment, the water washing is performed using deionized water for 1 to 5 minutes, preferably 5 minutes.

[0070] For reference, in the pretreatment, the time of acetone ultrasonic cleaning is 10 to 20 minutes, and the frequency is 20 to 50 kHz. Preferably, the time of acetone ultrasonic cleaning is 15 minutes, and the frequency is 30 to 40 kHz.

[0071] For reference, in the pretreatment, the ultrasonic cleaning time of deionized water is 10 to 20 minutes, and the frequency is 20 to 50 kHz. Preferably, the ultrasonic cleaning time of deionized water is 15 minutes, and the frequency is 30 to 40 kHz.

[0072] For reference, during the pretreatment, the drying temperature is 60-80°C for 1-3 hours, preferably 60°C for 2 hours.

[0073] Correspondingly, the present invention also provides a medical titanium-based metal functional coating prepared by the preparation method of any of the above embodiments.

[0074] The features and performance of the present invention are further described in detail below with reference to the embodiments.

[0075] Example 1

[0076] Vacuum-melted cast Ti17Nb2Fe was selected as the substrate, which was prepared by arc melting through the following steps:

[0077] (1) Weigh the pure metal particles required for alloy smelting. The mass of each alloy is controlled to be 30 ± 1 g. Specifically, the raw materials for each alloy include 20.891 g of Ti particles, 8.507 g of Nb particles, and 0.602 g of Fe particles. The purity of Ti, Nb, and Fe in the raw materials is 99.95%.

[0078] (2) Use a high vacuum arc melting furnace for melting. Before melting, introduce inert gas argon to repeatedly clean the vacuum melting furnace. Then, vacuum the melting furnace to 5×10 -3 Pa to ensure that there is no excess impurity gas in the furnace, and it is filled with argon as a protective gas.

[0079] (3) During the melting process, the electromagnetic stirrer was turned on to melt the sample into a round ingot. Each round ingot was turned over and remelted 6 times to ensure its uniformity. After cooling, it was taken out of the furnace.

[0080] The process of preparing the antibacterial and anti-corrosion functional coating on the metal surface is as follows:

[0081] (1) Pretreatment: After polishing Ti17Nb2Fe with waterproof silicon carbide sandpaper of 200, 600, 1000, 1500 and 2000 mesh, the surface residue attached to Ti17Nb2Fe was removed by deionized water washing for 5 min, and then ultrasonically cleaned with acetone, anhydrous ethanol and deionized water for 15 min (frequency of 40 kHz) respectively. Finally, it was placed in a vacuum drying oven at 60 °C and dried for 1 h before use.

[0082] (2) Alkali heat treatment: The Ti17Nb2Fe obtained in step (1) was immersed in a 5 mol / L NaOH solution, placed in a vacuum drying oven at 60°C for 24 h, taken out and rinsed with deionized water for 5 min, and finally placed in a vacuum drying oven at 60°C for 2 h for use.

[0083] (3) Ion Exchange: The Ti17Nb2Fe obtained in step (2) was immersed in a 0.1 mol / L HCl solution for 60 min, and then immersed in a 0.1 mol / L Mg(NO3)2·6H2O solution for 60 min. After removal, it was rinsed with deionized water for 5 min and finally dried in a 60°C vacuum drying oven for 2 h before use. After the ion exchange step, a magnesium titanate pre-coating was formed on the surface of the substrate.

[0084] (4) Hydrothermal treatment: The Ti17Nb2Fe obtained in step (3) was placed in the lining of the reactor, 160 mg of 2,5-dihydroxyterephthalic acid was weighed and dissolved in 50 mL of a mixed solvent, wherein the mixed solvent components and volume fraction ratio were N,N-dimethylformamide: anhydrous ethanol: deionized water = 15:3:2, and then 640 mg of magnesium nitrate and 8 mg of silver nitrate were added respectively. The mixture was ultrasonically stirred at 25°C for 60 min, and after stirring evenly, the mixture was poured into the lining of the reactor, and the reactor was tightened. Finally, the reactor was placed in a constant temperature forced air drying oven, kept warm at 125°C for 24 h, and taken out after cooling for standby use.

[0085] (5) The Ti17Nb2Fe obtained in step (4) was immersed in N,N-dimethylformamide solution for 20 minutes to dissolve the excess ligand, and then immersed in methanol solution for 2 hours to replace the N,N-dimethylformamide in the coating pores. Finally, it was placed in a vacuum drying oven at 100°C and dried for 3 hours to obtain the Mg / Ag-MOF74 antibacterial and anti-corrosion functional coating. The sample was labeled AHT-MgAg1.

[0086] The antibacterial and anti-corrosion functional coating prepared in this example was observed ( Figure 1 ), it can be found that uniform granules are generated on the surface of Ti17Nb2Fe, indicating that a uniform coating is constructed on the metal surface. At the same time, the EDS results ( Figure 2 ) It can be seen that Mg and Ag elements are detected, and the X-ray diffraction test ( Figure 3 ) detected the spectral peaks of Mg / Ag-MOF74 (such as 6.8° and 11.9°), indicating that the Mg / Ag-MOF74 coating was successfully constructed on the Ti17Nb2Fe surface.

[0087] The hydrophilic properties of Ti17Nb2Fe before and after coating preparation were obtained by water contact angle test ( Figure 4 Due to the characteristics of the porous structure of MOFs, it can be seen that the material modified with MgAg-MOF74 exhibits superhydrophilicity (6.5±0.3°), which has a positive effect on improving the activity of bone tissue in contact with the implant.

[0088] The corrosion resistance of Ti17Nb2Fe in simulated body fluids was obtained by potentiodynamic polarization curve test before and after coating preparation. Figure 5 ) It can be seen that the corrosion rate of Ti17Nb2Fe is significantly reduced (about 1 order of magnitude) after modification with MgAg-MOF74. At the same time, the coating has good uniformity. As a physical barrier layer, it makes the modified Ti17Nb2Fe have higher corrosion resistance.

[0089] Staphylococcus aureus (S. aureus) was selected as the microbial model and S. aureus was cultured in broth medium at 37°C on a shaker at 220 rpm overnight. The bacterial culture was diluted with fresh broth medium to an OD of 600 =0.10, after 3 hours of incubation, 100 μL of bacterial solution was evenly added to the Ti17Nb2Fe and AHT-MgAg1 surfaces of the 24-well plate, and the bacterial solution on the sample surface was collected after co-incubation at 37°C for 6 hours. The collected bacterial solution on the sample surface was diluted with PBS buffer, and the bacterial solution on the Ti17Nb2Fe surface was diluted 10 6 times, the bacterial solution on the AHT-MgAg1 surface was diluted 10 4 times, and finally, 100 μL was taken from 1 mL of bacterial solution and evenly spread on agar plates for overnight culture. The antibacterial ability of the samples was evaluated by calculating the number of viable bacteria (cfu) per unit volume (with Ti17Nb2Fe as the control group). The antibacterial rate was calculated as follows: The results showed that AHT-MgAg1 had a strong antibacterial effect on Staphylococcus aureus ( Figure 6 ), the antibacterial rate exceeds 99%, which shows that the material prepared in this embodiment has excellent antibacterial properties. + The effective antibacterial ability is also due to the certain antibacterial properties of the organic ligand DHTA. The two together ensure that the implant has a better antibacterial effect in the early stage of infection (within 4 to 6 hours).

[0090] Example 2

[0091] In this embodiment, commercially available cast CP-Ti is used as the substrate. The process for preparing the antibacterial and anti-corrosion functional coating on the metal surface is as follows:

[0092] (1) Pretreatment: After polishing CP-Ti with waterproof silicon carbide sandpaper of 200, 600, 1000, 1500 and 2000 mesh, the surface residue attached to CP-Ti was removed by deionized water rinse for 5 minutes, and then ultrasonically cleaned with acetone, anhydrous ethanol and deionized water for 10 minutes (frequency of 40kHz) respectively. Finally, it was placed in a vacuum drying oven at 80℃ and dried for 1 hour before use.

[0093] (2) Alkali heat treatment: The CP-Ti obtained in step (1) was immersed in a 3 mol / L NaOH solution, placed in a vacuum drying oven at 60°C for 36 h, taken out and rinsed with deionized water for 5 min, and finally placed in a vacuum drying oven at 80°C for 1 h for use.

[0094] (3) Ion Exchange: The CP-Ti obtained in step (2) was immersed in a 0.05 mol / L HCl solution for 60 min, then immersed in a 0.05 mol / L Mg(NO₃)₂·6H₂O solution for 60 min. After removal, the CP-Ti was rinsed with deionized water for 5 min and finally dried in a vacuum drying oven at 80°C for 1 h before use. After the ion exchange step, a magnesium titanate pre-coating was formed on the substrate surface.

[0095] (4) Hydrothermal treatment: The CP-Ti obtained in step (3) was placed in the lining of the reactor, 140 mg of 2,5-dihydroxyterephthalic acid was weighed and dissolved in 40 mL of a mixed solvent, wherein the mixed solvent components and volume fraction ratio were N,N-dimethylformamide: anhydrous ethanol: deionized water = 16:3:1, and then 550 mg of magnesium nitrate and 5 mg of silver nitrate were added respectively. The mixture was ultrasonically stirred at 35°C for 60 min, and after stirring evenly, the mixture was poured into the lining of the reactor, and the reactor was tightened. Finally, the reactor was placed in a constant temperature forced air drying oven and kept warm at 110°C for 36 h. After cooling, the mixture was taken out and set aside.

[0096] (5) The CP-Ti obtained in step (4) was immersed in N,N-dimethylformamide solution for 10 minutes to dissolve the excess ligand, and then immersed in methanol solution for 1 hour to replace the N,N-dimethylformamide in the coating pores. Finally, it was placed in a vacuum drying oven at 80°C and dried for 4 hours to obtain the Mg / Ag-MOF74 antibacterial and anti-corrosion functional coating. The sample was labeled AHT-MgAg2.

[0097] The antibacterial and anti-corrosion functional coating prepared in this example was observed ( Figure 1 ), it can be found that uniform particles are generated on the surface of CP-Ti, indicating that a uniform coating is constructed on the metal surface. At the same time, the EDS results ( Figure 2 ) It can be seen that Mg and Ag elements are detected, and the X-ray diffraction test ( Figure 3 ) detected the spectral peaks of Mg / Ag-MOF74 (such as 6.8° and 11.9°), indicating that the Mg / Ag-MOF74 coating was successfully constructed on the CP-Ti surface.

[0098] The hydrophilic properties of CP-Ti before and after coating preparation were obtained by water contact angle test ( Figure 4Due to the characteristics of the porous structure of MOFs, it can be seen that the material modified with MgAg-MOF74 exhibits superhydrophilicity (6.3±0.3°), which has a positive effect on improving the activity of bone tissue in contact with the implant.

[0099] Staphylococcus aureus (S. aureus) was selected as the microbial model and S. aureus was cultured in broth medium at 37°C on a shaker at 220 rpm overnight. The bacterial culture was diluted with fresh broth medium to an OD of 600 =0.10, after 3 hours of incubation, 100 μL of bacterial solution was evenly added to the CP-Ti and AHT-MgAg2 surfaces of a 24-well plate, and the bacterial solution on the sample surface was collected after co-incubation at 37°C for 6 hours. The collected bacterial solution on the sample surface was diluted with PBS buffer, and the bacterial solution on the CP-Ti surface was diluted 10 6 times, the bacterial solution on the AHT-MgAg2 surface was diluted 10 4 Finally, 100 μL of each 1 mL bacterial solution was evenly spread on an agar plate for overnight culture. The antibacterial ability of the sample was evaluated by calculating the number of viable bacteria (cfu) per unit volume (CP-Ti was used as the control group). The antibacterial rate was calculated as follows: The results showed that AHT-MgAg2 had a strong antibacterial effect on Staphylococcus aureus ( Figure 6 ), the antibacterial rate exceeds 99%, which shows that the material prepared in this embodiment has excellent antibacterial properties.

[0100] Example 3

[0101] In this embodiment, commercially available cast Ti6Al4V is used as the substrate. The process of preparing the antibacterial and anti-corrosion functional coating on the metal surface is as follows:

[0102] (1) Pretreatment: After polishing Ti6Al4V with waterproof silicon carbide sandpaper of 200, 600, 1000, 1500 and 2000 mesh, the surface residue attached to Ti6Al4V was removed by deionized water washing for 5 min, and then ultrasonic cleaning was carried out with acetone, anhydrous ethanol and deionized water for 20 min (frequency of 30 kHz) respectively. Finally, it was placed in a vacuum drying oven at 60 °C and dried for 3 h before use.

[0103] (2) Alkali heat treatment: The Ti6Al4V obtained in step (1) was immersed in 8 mol / L NaOH solution, placed in a vacuum drying oven at 90°C for 18 h, taken out and rinsed with deionized water for 5 min, and finally placed in a vacuum drying oven at 60°C for 3 h for use.

[0104] (3) Ion exchange: The Ti6Al4V obtained in step (2) was immersed in a 0.1 mol / L HCl solution for 30 min, and then immersed in a 0.1 mol / L Mg(NO3)2·6H2O solution for 30 min. After removal, it was rinsed with deionized water for 5 min and finally dried in a vacuum drying oven at 60°C for 3 h before use. After the ion exchange step, a magnesium titanate pre-coating was formed on the surface of the substrate.

[0105] (4) Hydrothermal treatment: The Ti6Al4V obtained in step (3) was placed in the lining of the reactor, 180 mg of 2,5-dihydroxyterephthalic acid was weighed and dissolved in 60 mL of a mixed solvent, wherein the mixed solvent components and volume fraction ratio were N,N-dimethylformamide: anhydrous ethanol: deionized water = 17:2:1, and then 720 mg of magnesium nitrate and 15 mg of silver nitrate were added respectively. The mixture was ultrasonically stirred at 25°C for 30 min, and after stirring evenly, the mixture was poured into the lining of the reactor, and the reactor was tightened. Finally, the reactor was placed in a constant temperature forced air drying oven, kept warm at 140°C for 18 h, and taken out after cooling for standby use.

[0106] (5) The Ti6Al4V obtained in step (4) was immersed in N,N-dimethylformamide solution for 30 minutes to dissolve the excess ligand, and then immersed in methanol solution for 3 hours to replace the N,N-dimethylformamide in the coating pores. Finally, it was placed in a vacuum drying oven at 100°C and dried for 2 hours to obtain the Mg / Ag-MOF74 antibacterial and anti-corrosion functional coating. The sample was labeled AHT-MgAg3.

[0107] The antibacterial and anti-corrosion functional coating prepared in this example was observed ( Figure 1 ), it can be found that uniform granules are generated on the surface of Ti6Al4V, indicating that a uniform coating is constructed on the metal surface. At the same time, the EDS results ( Figure 2 ) It can be seen that Mg and Ag elements are detected, and the X-ray diffraction test ( Figure 3 ) detected the spectral peaks of Mg / Ag-MOF74 (such as 6.8° and 11.9°), indicating that this embodiment successfully constructed a Mg / Ag-MOF74 coating on the Ti6Al4V surface.

[0108] The hydrophilic properties of Ti6Al4V before and after coating preparation were obtained by water contact angle test ( Figure 4 Due to the characteristics of the porous structure of MOFs, it can be seen that the material modified with MgAg-MOF74 exhibits superhydrophilicity (6.9±0.4°), which has a positive effect on improving the activity of bone tissue in contact with the implant.

[0109] Staphylococcus aureus (S. aureus) was selected as the microbial model and S. aureus was cultured in broth medium at 37°C on a shaker at 220 rpm overnight. The bacterial culture was diluted with fresh broth medium to an OD of 600 =0.10, after 3 hours of incubation, 100 μL of bacterial solution was evenly added to the Ti6Al4V and AHT-MgAg3 surfaces of a 24-well plate, and the bacterial solution on the sample surface was collected after co-incubation at 37°C for 6 hours. The collected bacterial solution on the sample surface was diluted with PBS buffer, and the bacterial solution on the Ti6Al4V surface was diluted 10 6 times, the bacterial solution on the AHT-MgAg3 surface was diluted 10 4 times, and finally, 100 μL was taken from 1 mL of bacterial solution and evenly spread on agar plates for overnight culture. The antibacterial ability of the sample was evaluated by calculating the number of viable bacteria (cfu) per unit volume (with Ti6Al4V as the control group). The antibacterial rate was calculated as follows: The results showed that AHT-MgAg3 had a strong antibacterial effect on Staphylococcus aureus ( Figure 6 ), the antibacterial rate exceeds 99%, which shows that the material prepared in this embodiment has excellent antibacterial properties.

[0110] Example 4

[0111] The difference between this embodiment and embodiment 1 is that the hydrothermal reaction conditions in step (4) are: keeping the temperature at 110° C. for 24 hours, and the other steps and parameters are the same as those in embodiment 1. The sample prepared in this embodiment is labeled AHT-MgAg4.

[0112] Example 5

[0113] The difference between this embodiment and embodiment 1 is that the hydrothermal reaction conditions in step (4) are: keeping the temperature at 125° C. for 18 hours; the other steps and parameters are the same as those in embodiment 1. The sample prepared in this embodiment is labeled AHT-MgAg5.

[0114] Example 6

[0115] The difference between this example and Example 1 is that the amount of metal salt added is 720 mg of magnesium nitrate and 15 mg of silver nitrate; the other steps and parameters are the same as those in Example 1. The sample prepared in this example is labeled AHT-MgAg6.

[0116] Comparing the six samples obtained in Examples 1 to 6, as shown in Table 1, the reaction temperature, time and amount of metal salt added (mainly silver nitrate) of the hydrothermal treatment have a significant effect on the thickness and stability of the coating. Among them, Example 1 is the best example, and the coating thickness and stability obtained therefrom are the best. Due to the different reaction temperatures and times, as well as the silver nitrate content, the morphology, thickness and stability of the coatings obtained in other examples are different from those in Example 1. However, from the perspective of antibacterial properties, each example has excellent antibacterial properties. From the perspective of the antibacterial properties of Example 2 and Example 3, coatings of different thicknesses have excellent antibacterial properties. In terms of corrosion resistance, Figure 5 It can be seen that although the coating thickness of Examples 4 to 6 is less than that of Example 1, and the stability and corrosion resistance are worse than that of Example 1, the corrosion rate of the samples modified with MgAg-MOF74 is significantly reduced compared with the unmodified Ti17Nb2Fe matrix. It can be seen that the coating acts as a physical barrier layer, which enables the modified Ti17Nb2Fe to have higher corrosion resistance.

[0117] Table 1 Coating thickness of Examples 1 to 6

[0118]

[0119]

[0120] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A method for preparing a medical titanium-based metal functional coating, characterized in that: The following steps are involved: The pretreated titanium-based metal substrate A is subjected to an alkali heat treatment, washed with water, and dried to obtain a hydroxylated substrate B; Substrate B is subjected to ion exchange, and then washed and dried to obtain substrate C; Magnesium nitrate and silver nitrate are used as metal salts, and 2,5-dihydroxyterephthalic acid is used as an organic ligand, which are dissolved in a solvent and mixed evenly to obtain a precursor solution. Substrate C is immersed in the precursor solution to undergo a hydrothermal reaction, and substrate D is obtained after cooling. The excess organic ligands in the substrate D are replaced, and after drying, a medical titanium-based metal functional coating is obtained; The solvent is a mixture solvent consisting of N,N-dimethylformamide, anhydrous ethanol and deionized water; in the precursor solution, the mass volume ratio of the magnesium nitrate to the mixture solvent is (550-720) mg: (40-60) mL; the mass volume ratio of the silver nitrate to the mixture solvent is (5-15) mg: (40-60) mL; and the mass volume ratio of the 2,5-dihydroxyterephthalic acid to the mixture solvent is (140-180) mg: (30-60) mL. The ion exchange step comprises immersing the substrate B in a hydrochloric acid solution and a magnesium nitrate solution in sequence to perform ion exchange, thereby forming a magnesium titanate pre-coating on the surface of the substrate B. In the ion exchange step, the concentration of the hydrochloric acid solution is 0.05 to 0.1 mol / L; the concentration of the magnesium nitrate solution is 0.05 to 0.1 mol / L. The method for replacing the excess organic ligands in the substrate D is as follows: immersing the substrate D in N,N-dimethylformamide and methanol respectively.

2. The preparation method according to claim 1, characterized in that In the mixture solvent, the volume fraction ratio is N,N-dimethylformamide:anhydrous ethanol:deionized water=(30-45):(1-9):(1-6).

3. The preparation method according to claim 1, characterized in that The hydrothermal reaction temperature is 110~140℃, and the insulation time is 18~36h.

4. The preparation method according to claim 1, characterized in that The precursor solution is uniformly mixed by ultrasonic stirring, the ultrasonic temperature is 25-35° C., and the time is 30-90 minutes.

5. The preparation method according to claim 1, wherein The alkaline heat treatment is to immerse the pretreated titanium-based metal substrate A in a sodium hydroxide solution with a concentration of 3 to 8 mol / L, and perform the alkaline heat treatment at 60 to 90° C. for 18 to 36 hours.

6. The preparation method according to claim 1, characterized in that The soaking time in the hydrochloric acid solution is 30~60 min; The soaking time in magnesium nitrate solution is 30~60 min; The washing time is 5 to 10 minutes; The drying temperature is 60~80℃ and the time is 1~3h.

7. The preparation method according to claim 1, characterized in that The substrate D is immersed in N,N-dimethylformamide for 10 to 30 minutes and in methanol for 1 to 3 hours; The drying method is vacuum drying, the temperature is 80~100℃, and the time is 2~4h.

8. The preparation method according to claim 1, characterized in that The pretreatment comprises the following steps: polishing the titanium-based metal with sandpaper and then washing with water, then ultrasonically cleaning with acetone, anhydrous ethanol and deionized water in sequence, and drying to obtain a pretreated titanium-based metal substrate A.

9. The preparation method according to claim 8, characterized in that In the pretreatment step, sandpaper polishing is to polish the titanium-based metal using waterproof silicon carbide sandpaper with mesh sizes of 200, 600, 1000, 1500 and 2000 in sequence; And / or, the washing is performed with deionized water for 1 to 5 minutes; and / or, acetone ultrasonic cleaning for 10 to 20 minutes at a frequency of 20 to 50 kHz; and / or, ultrasonic cleaning with anhydrous ethanol for 10 to 20 minutes at a frequency of 20 to 50 kHz; and / or, ultrasonic cleaning with deionized water for 10 to 20 minutes at a frequency of 20 to 50 kHz; and / or, the drying temperature is 60-80°C and the drying time is 1-3 h.

10. A medical titanium-based metal functional coating, characterized in that: It is prepared by the preparation method according to any one of claims 1 to 9.

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