A method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes

Abstract

The application provides a method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes, and solves the technical problem that a bactericide polyvinylpyrrolidone cannot be directly coated on the surface of medical titanium material to form stable combination. The application first prepares an ordered titanium nanotube array on the surface of a pure titanium sheet through an anodic oxidation method, then introduces polyvinylpyrrolidone into the surface of the titanium nanotube array through a mussel bionic chemical grafting method by using dopamine, and finally successfully fixes iodine on the surface of the titanium nanotube array by complexing polyvinylpyrrolidone on the surface of the titanium nanotube array with iodine under mild conditions, so that a medical titanium modified material with a polyvinylpyrrolidone-iodine coating on the surface of the titanium nanotube is obtained, and the titanium material implant is endowed with good anti-infection performance. Compared with the prior art, the application is simple and efficient, the required experimental equipment is simple, the reaction conditions are mild, and the application is more conducive to the amplification of the operation process and industrialized production.

Description

Technical Field

[0001] This invention belongs to the field of materials technology, and specifically relates to a method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes. Background Technology

[0002] Titanium implants are a common metal-based bone implant material due to their good mechanical properties and corrosion resistance. However, because they do not have antibacterial properties, they face the risk of bacterial infection during clinical application, which is one of the main problems faced by titanium implants in the field of bone implantation.

[0003] Antibiotics are commonly used in clinical practice to treat bacterial infections in implants; however, the overuse of antibiotics has led to increasingly serious problems of bacterial resistance. Therefore, developing titanium implants with good antibacterial properties and low resistance to drug development through surface antibacterial treatment has become a research hotspot in recent years. Antibacterial polymers are often used to modify the antibacterial properties of material surfaces due to their wide variety, modifiability, tunable biocompatibility, long-lasting antibacterial activity, and low resistance to drug development. Among many antibacterial polymers, povidone-iodine (iodophor), an amorphous conjugate of iodine and polyvinylpyrrolidone (PVP), is widely used as a broad-spectrum bactericide in medicine. However, the good water solubility of the PVP-iodine complex makes its stable formation on titanium surfaces relatively difficult.

[0004] Chinese patent CN 111705347 B provides a method for preparing iodine coatings on titanium nanotubes by chemical vapor deposition and its application. However, the preparation process requires specialized chemical vapor deposition equipment, the reaction process is not convenient or fast, and the production cost is high.

[0005] Therefore, it is necessary to provide a simpler, more efficient, and more economical method for preparing titanium nanotube polyvinylpyrrolidone-iodine coatings. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of existing techniques for preparing titanium nanotube iodine coatings, which are not simple enough, and to provide a method for preparing titanium nanotube polyvinylpyrrolidone-iodine coatings on the surface of titanium materials.

[0007] To achieve the above objectives, the technical solution provided by this invention is:

[0008] A method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes, characterized by comprising the following steps:

[0009] 1) Preparation of titanium nanotubes on the surface of titanium materials

[0010] Titanium nanotube arrays (TNTs) were prepared on the surface of titanium (Ti) by anodizing, followed by annealing and ultrasonic cleaning to obtain titanium material with titanium nanotubes on the surface.

[0011] 2) Grafting polyvinylpyrrolidone onto the surface of titanium nanotubes

[0012] The titanium material with titanium nanotubes on its surface obtained in step 1) was completely immersed in a Tris-HCl buffer solution with pH 8.5 containing dopamine (DA) and polyvinylpyrrolidone (PVP) to carry out the reaction. After the reaction was completed, it was cleaned and dried to obtain titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone on the surface of the titanium material.

[0013] 3) Preparation of titanium nanotube polyvinylpyrrolidone-iodine coating on titanium material surface

[0014] The titanium material obtained in step 2) was immersed in an ethanol solution of iodine to carry out a complexation reaction between polyvinylpyrrolidone (PVP) and iodine. Ethanol was prevented from evaporating during the reaction. After the reaction was completed, the free iodine was washed off and the material was dried to obtain a titanium material with a titanium nanotube polyvinylpyrrolidone-iodine coating on the surface, namely TNT-DP-I.

[0015] Furthermore, step 1) specifically involves:

[0016] An electrolyte was prepared by mixing ammonium fluoride, ultrapure water, and ethylene glycol. A constant-voltage DC anodic oxidation method was used, with a cleaned titanium sheet as the anode and a platinum sheet as the cathode. The working voltage was fixed at 60V, and the anodic oxidation reaction time was 2 hours. After the reaction, the sheet was removed and ultrasonically cleaned with deionized water and ethanol in sequence. It was then placed in a tube furnace and annealed at 460-550℃ (preferably 550℃, which ensures that the nanotubes will not collapse and will transform from an amorphous to a crystalline state) for 2 hours. After natural cooling, the sheet was removed, ultrasonically cleaned with deionized water and ethanol, and dried to obtain a titanium sheet with titanium nanotubes on its surface. Under these conditions, the prepared titanium nanotubes have a diameter of 90 nm and a length of 10 μm. The diameter and length of the titanium nanotubes are closely related to the drug loading capacity, so the diameter and length are important factors affecting the subsequent progress of this invention. Using the anodic oxidation electrolyte and reaction parameters in this invention, titanium nanotubes with a length of 10 μm and a diameter of 90 nm can be prepared in a reaction time of 2 hours. This fully meets the requirement that TNT with a diameter of less than 100 nm will not inhibit osteoblast growth, proliferation and adhesion. It can be seen that this invention optimizes the length of titanium nanotubes while meeting the requirements.

[0017] In this process, ammonium fluoride is weighed into a beaker, and then ultrapure water and ethylene glycol are added to prepare the electrolyte. The molar ratio of ammonium fluoride, ultrapure water and ethylene glycol is 1:14-15:237-238.

[0018] Regarding the specificity of the selection of the anodic oxidation electrolyte and reaction parameters in this invention, the research team of this invention selected them in the following manner:

[0019] First, a reaction time of 2 hours was selected, and working voltages of 20V, 40V, 60V, and 80V were set. It was observed that the diameter of titanium nanotubes gradually increased with increasing voltage: at 60V, the TNT diameter was approximately 90nm. At 80V, the nanotube diameter reached approximately 120nm (greater than 100nm would inhibit osteoblast growth, proliferation, and adhesion). Therefore, considering all factors, 60V was chosen as the working voltage for subsequent experiments. Furthermore, with the working voltage fixed at 60V, the effects of different reaction times (1h, 2h, 3h, and 5h) on the TNT diameter and length were explored. At the same voltage, the reaction time did not significantly affect the TNT diameter; however, the nanotube length increased with increasing reaction time. The TNT nanotubes prepared with reaction times of 1h, 2h, 3h, and 5h had lengths of 4μm, 10μm, 15μm, and 25μm, respectively. The nanotube length significantly affects the drug loading capacity. While drug loading increases with surface area, excessively long nanotubes can negatively impact the mechanical strength of the material surface. Therefore, this invention selected a suitable length of 10μm for further investigation. This application ultimately chose a working voltage of 60V and a reaction time of 2h as the parameters for subsequent experiments. These process conditions, combined with different electrolyte formulations, yielded significantly better results than existing techniques for preparing titanium nanotubes (which are time-consuming and have excessively short nanotube lengths).

[0020] Further, in step 2), the dopamine and polyvinylpyrrolidone are in a Tris-HCl buffer solution with a pH of 8.5, the density of both dopamine and polyvinylpyrrolidone is 2 mg / mL, and the molar concentration of the Tris-HCl buffer solution is 10 mM.

[0021] Furthermore, in step 2), during immersion, the titanium sheet with titanium nanotubes on its surface is fixed (clamps can be used for fixation) to ensure that the surface of the titanium sheet is in full contact with the liquid. The reaction time is 3 hours. After the reaction is completed, ultrasonic cleaning with ethanol is performed.

[0022] Furthermore, in step 3), the iodine in the ethanol solution has a mass fraction of 5 wt%; and the complexation reaction takes 3 to 24 hours, preferably 3 hours, which is sufficient for complexation.

[0023] Furthermore, in step 3), during immersion, the titanium sheet obtained in step 2) is fixed (using clips) to ensure that the surface of the titanium sheet is in full contact with the liquid, and ethanol evaporation is prevented by sealing the opening of the reaction vessel with a sealing film.

[0024] The drying in steps 2) and 3) is carried out in a drying oven.

[0025] Meanwhile, this invention provides a method for preparing a titanium nanotube polyvinylpyrrolidone-iodine coating using the above method and its application as an antibacterial coating on the surface of biomedical titanium materials.

[0026] Based on the application of the above coating, the present invention also provides a biomedical modified titanium material, which is special in that a titanium nanotube polyvinylpyrrolidone-iodine coating is prepared on the surface of the biomedical titanium material according to the above method.

[0027] A medical device, the material of which is the aforementioned biomedical titanium-modified material.

[0028] Mechanism of the invention:

[0029] This invention first prepares an ordered array of titanium nanotubes (TNTs) on the surface of a pure titanium sheet using an anodic oxidation method. Then, using a mussel-inspired biochemical grafting method, polyvinylpyrrolidone (PVP) is introduced onto the surface of the TNTs using dopamine (DA). Finally, under mild conditions, PVP on the TNT surface complexes with iodine, fixing iodine onto the TNT surface (i.e., iodine is stably bound through the complexation of PVP and iodine). This forms a stable, bactericidal PVP-iodine complex coating on the surface of the titanium implant, resulting in a medical-grade modified titanium material with a titanium nanotube PVP-iodine coating, thus endowing the titanium implant with excellent anti-infection properties.

[0030] The advantages of this invention are:

[0031] This invention employs a mussel-inspired biomimetic chemical grafting method to effectively prepare a polyvinylpyrrolidone-iodine coating on the surface of titanium dioxide nanotubes (TNT). The operation process is simple. Furthermore, compared with existing technologies, the required experimental equipment is simpler, the reaction conditions are milder, and the method of directly using dopamine for chemical grafting can also obtain a polyvinylpyrrolidone-iodine coating with good adhesion and antibacterial effect. This method, while being simpler, more efficient, and having milder reaction conditions, also produces a coating with good adhesion and imparts good antibacterial properties to the implant. Given the simplicity and efficiency of this invention, it is more conducive to the practical scale-up and industrial production of the process. Attached Figure Description

[0032] Figure 1 This is a schematic diagram of the preparation of TNT-DP-I on titanium material in Embodiment 1 of the present invention, wherein a is a preparation flowchart and b is a detailed schematic diagram of the complexation of TNT-DP sample with iodine;

[0033] Figure 2 These are SEM images of TNT prepared on titanium material in Comparative Example 2 of this invention, where a is the surface morphology and b is a cross-sectional view;

[0034] Figure 3 These are SEM surface morphology images of TNT-DP-I prepared on titanium material according to Examples 1, 2, 3 and 4 of the present invention, wherein a is Example 1, b is Example 2, c is Example 3 and d is Example 4;

[0035] Figure 4 These are surface morphology diagrams of the samples prepared in Comparative Example 1, Comparative Example 2, Comparative Example 3, and Example 1;

[0036] Figure 5 SEM surface morphology images of the samples prepared in Comparative Examples 1, 2, 3 and Example 1 for antibacterial activity testing.

[0037] Figure 6 These are cell viability test graphs of the samples prepared in Comparative Example 2, Comparative Example 3, and Example 1;

[0038] Figure 7 These are hemolysis test photographs and hemolysis rate graphs of the samples prepared in Comparative Examples 1, 2, 3 and Example 1, where a is a hemolysis test photograph and b is a hemolysis rate graph.

[0039] Figure 8 The images show Live / Dead experiments and cell morphology fluorescence microscopy images of Comparative Examples 1, 2, 3, and 1 with osteoblasts for 1 day, 3 days, and 5 days; where a is a Live / Dead experiment image for 1 day, b is a Live / Dead experiment image for 3 days, c is a Live / Dead experiment image for 5 days, and d is a cell morphology fluorescence microscopy image.

[0040] Figure 9 These are SEM images of Comparative Examples 1, 2, and 3, as well as Example 1, after incubation with osteoblasts for 1 and 3 days. Detailed Implementation

[0041] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments:

[0042] like Figure 1 As shown in the process flow diagram, this invention proposes a method for preparing a titanium nanotube polyvinylpyrrolidone-iodine coating on the surface of titanium material using a mussel-inspired biomimetic chemical grafting method, comprising the following steps:

[0043] 1) Cut a 0.4cm thick titanium sheet into 1cm×1cm pieces, and clean it with ethanol and ultrapure water at a frequency of 100Hz for 5 minutes in sequence, then dry it for later use.

[0044] Preparation of titanium electrodes: cut titanium sheets into 1cm×3cm pieces, and clean them sequentially with ethanol and ultrapure water at a frequency of 100Hz for 5min, then dry them for later use.

[0045] 2) Prepare the electrolyte by mixing 0.7g ammonium fluoride, 5mL ultrapure water, and 250mL ethylene glycol. Then fix the titanium electrode, connect the power supply, fix the working voltage at 60V, and set the reaction time to 2h. After the anodizing is completed, remove the titanium sheet with titanium nanotubes (TNT) on the surface and ultrasonically clean it with deionized water and ethanol.

[0046] The titanium sheet with titanium nanotubes (TNT) on its surface, prepared above, was placed in the center of a quartz tube in a tubular furnace and heated to 460–550 °C (preferably 550 °C, as samples treated at this temperature tend to exhibit a coexistence of anatase and rutile phases, resulting in a more thorough phase transformation) at a heating rate of 5 °C / min. After annealing for 2 hours and natural cooling, the sample was removed and ultrasonically cleaned with ethanol and deionized water. The titanium nanotubes prepared under these conditions had a diameter of 90 nm and a length of 10 μm.

[0047] 3) Prepare a Tris-HCl solution (pH=8.5) of 2 mg / mL dopamine (DA) and polyvinylpyrrolidone (PVP) in a beaker. Fix the titanium sheet with titanium nanotubes (TNT) on the surface prepared above on the rack so that the titanium sheet is completely immersed below the liquid surface. After deposition at room temperature for 3 hours, ultrasonically clean it with ethanol and dry it to obtain a titanium sheet with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone.

[0048] 4) Prepare a 5wt% iodine ethanol solution. Fix the titanium sheet with titanium nanotubes grafted with polyvinylpyrrolidone (TNT-DP) onto its surface using a clamp and immerse it in the iodine solution. Seal the mouth of the beaker with sealing film to prevent ethanol evaporation. React at room temperature for 3–24 hours. After the reaction is complete, soak in ethanol and ultrasonically clean. Dry to obtain a titanium sheet with a titanium nanotube polyvinylpyrrolidone-iodine coating (TNT-DP-I).

[0049] Example 1

[0050] A method for preparing titanium nanotube polypyrrole-iodine coatings using a mussel-inspired biomimetic chemical grafting method includes the following steps:

[0051] First, cut pure titanium sheets into samples of a certain size (1cm×1cm), then use ethanol and ultrapure water to ultrasonically clean them for 5 minutes in sequence, and then dry them for later use.

[0052] An electrolyte was prepared by mixing 0.7 g ammonium fluoride, 5 mL ultrapure water, and 250 mL ethylene glycol. The titanium electrode was then fixed, a power supply was connected, the operating voltage was fixed at 60 V, and the reaction time was set to 2 h. After anodizing, the titanium sheet with titanium nanotubes (TNT) on its surface was removed and ultrasonically cleaned sequentially with deionized water and ethanol. The resulting titanium sheet with TNT on its surface was placed in the center of a quartz tube in a tubular furnace and heated to 550 °C at a heating rate of 5 °C / min. Annealing was performed for 2 h, and after natural cooling, it was removed and ultrasonically cleaned with ethanol and deionized water.

[0053] A 2 mg / mL mixed solution of DA and PVP was prepared using 10 mM Tris-HCl solution (pH = 8.5) as solvent. The titanium sheet with titanium nanotubes (TNT) on its surface was fixed on a frame and completely immersed in the DA and PVP mixed solution. After deposition at room temperature for 3 h, it was ultrasonically cleaned with ethanol and dried to obtain a titanium sheet with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone.

[0054] A 5 wt% iodine ethanol solution was prepared. Titanium sheets with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone (PVP) were fixed in the iodine solution using clips and immersed in the solution. The mouth of the beaker was sealed with sealing film to prevent ethanol evaporation, and the reaction was carried out at room temperature for 3 hours. After the reaction, the sheets were soaked in ethanol, ultrasonically cleaned, and dried to obtain titanium sheets with a TNT-DP-I coating on the surface of titanium nanotubes with PPVP-DP.

[0055] Comparative Example 1

[0056] Pure titanium sheets were cut into samples of a certain size (1cm × 1cm), then ultrasonically cleaned with ethanol and ultrapure water for 5 minutes in sequence, and then dried for later use. The product is a cleaned titanium sheet.

[0057] Comparative Example 2

[0058] First, cut pure titanium sheets into samples of a certain size (1cm×1cm), then use ethanol and ultrapure water to ultrasonically clean them for 5 minutes in sequence, and then dry them for later use.

[0059] An electrolyte was prepared by mixing 0.7 g ammonium fluoride, 5 mL ultrapure water, and 250 mL ethylene glycol. A titanium electrode was then fixed, a power supply was connected, the operating voltage was fixed at 60 V, and the reaction time was set to 2 h. After anodizing, the titanium sheet with titanium nanotubes (TNT) on its surface was removed and ultrasonically cleaned with deionized water and ethanol. The prepared TNT was placed in the center of a quartz tube in a tubular furnace and heated to 550 °C at a heating rate of 5 °C / min. Annealing was performed for 2 h, and after natural cooling, the sheet was removed and ultrasonically cleaned with ethanol and deionized water to obtain a clean titanium sheet with titanium nanotubes (TNT) on its surface.

[0060] Comparative Example 3

[0061] Pure titanium sheets were cut into samples of a certain size (1cm×1cm), and then ultrasonically cleaned with ethanol and ultrapure water for 5 minutes in sequence before drying for later use.

[0062] An electrolyte was prepared by mixing 0.7 g ammonium fluoride, 5 mL ultrapure water, and 250 mL ethylene glycol. The titanium electrode was then fixed, a power supply was connected, the operating voltage was fixed at 60 V, and the reaction time was set to 2 h. After anodizing, the titanium sheet with titanium nanotubes (TNT) on its surface was removed and ultrasonically cleaned with deionized water and ethanol. The resulting titanium sheet with titanium nanotubes was placed in the center of a tubular furnace quartz tube and heated to 550 °C at a heating rate of 5 °C / min. Annealing was performed for 2 h, and after natural cooling, it was removed and ultrasonically cleaned with ethanol and deionized water.

[0063] A 2 mg / mL mixed solution of DA and PVP was prepared using 10 mM Tris-HCl solution (pH = 8.5) as solvent. The titanium sheet with titanium nanotubes on its surface was fixed on a rack and completely immersed in the DA and PVP mixed solution. After deposition at room temperature for 2 h, it was ultrasonically cleaned with ethanol and dried to obtain a titanium sheet with titanium nanotubes (TNT-DP) grafted onto its surface.

[0064] Example 2

[0065] A method for preparing titanium nanotube polypyrrole-iodine coatings using a mussel-inspired biomimetic chemical grafting method includes the following steps:

[0066] Pure titanium sheets were cut into samples of a certain size (1cm×1cm), and then ultrasonically cleaned with ethanol and ultrapure water for 5 minutes in sequence before drying for later use.

[0067] An electrolyte was prepared by mixing 0.7 g ammonium fluoride, 5 mL ultrapure water, and 250 mL ethylene glycol. The titanium electrode was then fixed, a power supply was connected, the operating voltage was fixed at 60 V, and the reaction time was set to 2 h. After anodizing, the titanium sheet with titanium nanotubes (TNT) on its surface was removed and ultrasonically cleaned with deionized water and ethanol. The titanium sheet with TNT on its surface was then placed in the center of a tubular furnace quartz tube and heated to 550 °C at a heating rate of 5 °C / min for annealing for 2 h. After natural cooling, it was removed and ultrasonically cleaned with ethanol and deionized water.

[0068] A 2 mg / mL mixed solution of DA and PVP was prepared using 10 mM Tris-HCl solution (pH = 8.5) as solvent. The titanium sheet with titanium nanotubes on its surface was fixed on a rack and completely immersed in the DA and PVP mixed solution. After deposition at room temperature for 2 h, it was ultrasonically cleaned with ethanol and dried to obtain a titanium sheet with titanium nanotubes (TNT-DP) grafted onto its surface.

[0069] A 5 wt% iodine ethanol solution was prepared. Titanium sheets with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone (PVP) were fixed in the iodine solution using clamps and immersed in the solution. The mouth of the beaker was sealed with sealing film to prevent ethanol evaporation, and the reaction was carried out at room temperature for 6 hours. After the reaction, the sheets were soaked in ethanol, ultrasonically cleaned, and dried to obtain titanium sheets with a TNT-DP-I coating on the surface of titanium nanotubes with PPVP-DP.

[0070] Example 3

[0071] A method for preparing titanium nanotube polypyrrole-iodine coatings using a mussel-inspired biomimetic chemical grafting method includes the following steps:

[0072] Pure titanium sheets were cut into samples of a certain size (1cm×1cm), and then ultrasonically cleaned with ethanol and ultrapure water for 5 minutes in sequence before drying for later use.

[0073] An electrolyte was prepared by mixing 0.7 g ammonium fluoride, 5 mL ultrapure water, and 250 mL ethylene glycol. The titanium electrode was then fixed, a power supply was connected, the operating voltage was fixed at 60 V, and the reaction time was set to 2 h. After anodizing, the titanium sheet with titanium nanotubes (TNT) on its surface was removed and ultrasonically cleaned with deionized water and ethanol. The resulting titanium sheet with TNT on its surface was placed in the center of a tubular furnace quartz tube and heated to 550 °C at a heating rate of 5 °C / min. Annealing was performed for 2 h, and after natural cooling, it was removed and ultrasonically cleaned with ethanol and deionized water.

[0074] A 2 mg / mL mixed solution of DA and PVP was prepared using 10 mM Tris-HCl solution (pH = 8.5) as solvent. The titanium sheet with titanium nanotubes (TNT) on its surface was fixed on a rack and completely immersed in the DA and PVP mixed solution. After deposition at room temperature for 2 h, it was ultrasonically cleaned with ethanol and dried to obtain a titanium sheet with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone.

[0075] A 5 wt% iodine ethanol solution was prepared. Titanium sheets with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone (PVP) were fixed in the iodine solution using clamps and immersed in the solution. The mouth of the beaker was sealed with a sealing film to prevent ethanol evaporation, and the reaction was carried out at room temperature for 12 hours. After the reaction, the sheets were soaked in ethanol, ultrasonically cleaned, and dried to obtain titanium sheets with a TNT-DP-I coating on the surface of titanium nanotubes with PPVP-DP.

[0076] Example 4

[0077] A method for preparing titanium nanotube polypyrrole-iodine coatings using a mussel-inspired biomimetic chemical grafting method includes the following steps:

[0078] First, cut pure titanium sheets into samples of a certain size (1cm×1cm), then use ethanol and ultrapure water to ultrasonically clean them for 5 minutes in sequence, and then dry them for later use.

[0079] An electrolyte was prepared by mixing 0.7 g ammonium fluoride, 5 mL ultrapure water, and 250 mL ethylene glycol. The titanium electrode was then fixed, a power supply was connected, the operating voltage was fixed at 60 V, and the reaction time was set to 2 h. After anodizing, the titanium sheet with titanium nanotubes (TNT) on its surface was removed and ultrasonically cleaned with deionized water and ethanol. The resulting titanium sheet with TNT on its surface was placed in the center of a tubular furnace quartz tube and heated to 550 °C at a heating rate of 5 °C / min. Annealing was performed for 2 h, and after natural cooling, it was removed and ultrasonically cleaned with ethanol and deionized water.

[0080] A 2 mg / mL mixed solution of DA and PVP was prepared using 10 mM Tris-HCl solution (pH = 8.5) as solvent. The titanium sheet with titanium nanotubes (TNT) on its surface was fixed on a rack and completely immersed in the DA and PVP mixed solution. After deposition at room temperature for 2 h, it was ultrasonically cleaned with ethanol and dried to obtain a titanium sheet with titanium nanotubes (TNT-DP) grafted with polyvinylpyrrolidone.

[0081] A 5 wt% iodine ethanol solution was prepared. Titanium sheets with polyvinylpyrrolidone (PVP)-grafted titanium nanotubes (TNT-DP) were fixed in the iodine solution using clamps and immersed in the solution. The mouth of the beaker was sealed with sealing film to prevent ethanol evaporation, and the reaction was carried out at room temperature for 24 hours. After the reaction, the sheets were soaked in ethanol, ultrasonically cleaned, and dried to obtain titanium sheets with a TNT-DP-I coating on the surface of titanium nanotube PPVP-iodine.

[0082] To further understand the morphology and effects of the products prepared by this invention, the following verifications were also conducted:

[0083] 1. Comparative Example 2, which was prepared using the same method as Example 1, was characterized by SEM, such as... Figure 2 As shown, the surface pores are uniform, with a pore size of about 90 nm, and have a suitable tube length (about 10 μm). The SEM results further demonstrate the successful preparation of TNT.

[0084] 2. This invention investigated the effect of iodine deposition time on the surface morphology of TNT, from... Figure 3 It is known that as the deposition time increases, TNT will gradually become blocked and lose its orderly pore structure, which is not conducive to the adhesion, growth and proliferation of osteoblasts. Therefore, this application prefers to use 5wt% iodine solution for deposition for 3h to preserve the tubular structure of TNT, that is, to use Example 1 as the basis for subsequent experiments.

[0085] 3. By Figure 4It can be seen that, compared with Comparative Example 1, Comparative Example 2, Comparative Example 3, and Example 1 all exhibit a distinct TNT structure, and their surface morphology did not change significantly after deposition of the polyvinylpyrrolidone-iodine complex. To test the antibacterial properties of the coating, this invention tested the killing ability of samples Ti, TNT, TNT-DP, and TNT-DP-I against different bacterial species (E. coli and S. aureus). FESEM was used to observe the morphological changes of bacteria before and after contact with the materials Ti, TNT, TNT-DP, and TNT-DP-I.

[0086] 4. For example Figure 5 As shown, *S. aureus* and *E. coli* on the surfaces of Ti, TNT, and TNT-DP materials retained their original morphology, with smooth bacterial surfaces, indicating that they did not possess significant antibacterial properties. However, the *S. aureus* and *E. coli* bacteria treated with the TNT-DP-I sample group showed significant surface shrinkage and leakage of bacterial contents, indicating that TNT-DP-I has a strong bactericidal ability and also demonstrating the successful preparation of a polyvinylpyrrolidone-iodine coating on titanium surfaces.

[0087] 5. For implant materials, good biocompatibility is essential. This invention uses MC3T3 osteoblasts to evaluate the cytocompatibility of the coating and Alamar Blue to test the cytotoxicity of different samples (Ti as control, TNT, TNT-DP, and TNT-DP-I). Experimental results are as follows: Figure 6 The results showed that the cell survival rate in the TNT, TNT-DP, and TNT-DP-I groups was approximately 100%, indicating that the viability and proliferation of cells cultured on the sample surface were at the same level as those on pure titanium sheets. In other words, none of the sample groups affected osteoblast survival, demonstrating good biocompatibility.

[0088] 6. In addition, this invention investigated the blood compatibility of each group of samples, such as... Figure 7 As shown, no hemolysis occurred after blood cells were incubated with the surfaces of all samples for one hour. However, in the negative control group, Triton X-100, most blood cells ruptured after 1 hour of incubation, showing obvious hemolysis, demonstrating that the modified material TNT-DP-I obtained in the embodiments of the present invention has good blood compatibility.

[0089] 7. This invention used Live / Dead staining and cytoskeleton staining to investigate the effects of each group of samples on cell proliferation and adhesion. Live / Dead staining results are shown below. Figure 8 As shown in figures a, b, and c, no obvious dead cells were found in any of the groups, indicating that Comparative Examples 1, 2, and 3, as well as the Example 1, all promoted cell proliferation. The scaffold staining results are as follows: Figure 8As shown in d, the results indicate that, compared with Comparative Example 1, after incubation with MC3T3 osteoblasts for 24 h, the cells on the TNT-DP-I group material spread well and obvious pseudopodia were observed, indicating that TNT-DP-I can promote cell adhesion.

[0090] 8. To further observe cell adhesion on the material surface, this invention used FESEM to characterize cell morphology. For example... Figure 9 As shown, there is a significant difference between the cells on the surface of the experimental group and the cells on the surface of the titanium sheet: the number of cells on the surface of the material in the example is greater than that on the surface of the Ti in the comparative example, and the cells all show a stretched state, and pseudopodia structure of the cells can be observed, which further indicates that the TNT-DP-I surface is conducive to the adhesion, growth and proliferation of osteoblasts.

[0091] In summary, the method for preparing titanium nanotube polyvinylpyrrolidone-iodine coatings on titanium surfaces and the titanium nanotube polyvinylpyrrolidone-iodine coatings prepared by this method have good application prospects in biomedical titanium surfaces and even medical devices.

[0092] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the scope of the technology disclosed in the present invention, and such modifications or substitutions should all be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes, characterized in that, Includes the following steps: 1) Preparation of titanium nanotubes on the surface of titanium materials Titanium nanotube arrays were prepared on the surface of titanium material by anodizing, followed by annealing and ultrasonic cleaning to obtain titanium material with titanium nanotubes on the surface; the diameter of the titanium nanotubes was 90 nm and the length was 10 μm. 2) Grafting polyvinylpyrrolidone onto the surface of titanium nanotubes The titanium material with titanium nanotubes on its surface obtained in step 1) was immersed in a Tris-HCl buffer solution of dopamine and polyvinylpyrrolidone at pH 8.5 for reaction. After 2-3 hours of reaction, it was washed and dried to obtain titanium nanotubes with polyvinylpyrrolidone grafted on its surface. In a Tris-HCl buffer solution with pH 8.5, the densities of dopamine and polyvinylpyrrolidone are both 2 mg / mL, and the molar concentration of the Tris-HCl buffer solution is 10 mM. 3) Preparation of titanium nanotube polyvinylpyrrolidone-iodine coating on titanium material surface The titanium material obtained in step 2) was immersed in an iodine-ethanol solution to carry out a complexation reaction between polyvinylpyrrolidone and iodine. During the reaction, the opening of the reaction container was sealed with a sealing film to prevent ethanol evaporation. After the reaction was carried out for 3 to 24 hours, the material was cleaned and dried to obtain a titanium material with a titanium nanotube polyvinylpyrrolidone-iodine coating on its surface.

2. The method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes according to claim 1, characterized in that, Step 1) specifically involves: An electrolyte was prepared by mixing ammonium fluoride, ultrapure water, and ethylene glycol. A constant voltage DC anodic oxidation method was used, with a cleaned titanium sheet as the anode and a platinum sheet as the cathode. The working voltage was fixed at 60V, and the anodic oxidation reaction time was 2 hours. After the reaction was completed, the sheet was removed, cleaned, and placed in a tube furnace. It was annealed at 460-550℃ for 2 hours and then naturally cooled. After cleaning and drying, a titanium sheet with titanium nanotubes on its surface was obtained. In this process, ammonium fluoride is weighed into a beaker, and then ultrapure water and ethylene glycol are added to prepare the electrolyte. The molar ratio of ammonium fluoride, ultrapure water and ethylene glycol is 1:14-15:237-238.

3. The method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes according to claim 2, characterized in that... : In step 2), during immersion, the titanium sheet with titanium nanotubes on its surface is fixed to ensure that the surface of the titanium material is in full contact with the liquid. The reaction time is 3 hours. After the reaction is completed, ultrasonic cleaning with ethanol is performed.

4. The method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes according to claim 3, characterized in that... : In step 3), the iodine in the ethanol solution has a mass fraction of 5 wt%.

5. The method for preparing a polyvinylpyrrolidone-iodine coating on the surface of titanium nanotubes according to claim 4, characterized in that... : In step 3), during immersion, the titanium sheet obtained in step 2) is fixed to ensure that the surface of the titanium sheet is in full contact with the liquid.

6. A titanium nanotube polyvinylpyrrolidone-iodine coating, characterized in that: It is prepared by any one of the methods described in claims 1-5.

7. The application of the titanium nanotube polyvinylpyrrolidone-iodine coating prepared by any of the methods of claims 1-5 as an antibacterial coating on the surface of biomedical titanium materials.

8. A biomedical titanium-modified material, characterized in that: A titanium nanotube polyvinylpyrrolidone-iodine coating is prepared on the surface of a biomedical titanium material according to any one of the methods described in claims 1-5.

9. A medical device, characterized in that: The material used is the biomedical titanium-modified material described in claim 8.

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