CN103520776B - Medical titanium substrate material and manufacturing method thereof - Google Patents

Abstract

The invention provides a medical titanium base material, which comprises a titanium base and an anatase titanium dioxide film layer with a micro/nano multi-level composite hole structure formed on the surface of the titanium base. The present invention also provides a method for manufacturing a medical titanium base material, which includes the following steps in sequence: performing surface pretreatment on the titanium base, including polishing and cleaning steps; performing acid etching treatment, and the acid etching solution is a mixed solution of sulfuric acid and hydrochloric acid, After acid etching treatment, a micron-scale pore structure is formed on the surface of the titanium substrate, and anodic oxidation treatment is performed. After anodic oxidation treatment, a nano-scale pore structure is formed on the micron-scale structure, that is, a micron/nano multi-level composite pore structure is formed. ; Carry out heat treatment, and form an anatase titanium dioxide film layer with micron/nano multi-level composite pore structure on the surface of the titanium base material after the heat treatment.

Description

A kind of medical titanium base material and its manufacturing method

technical field

The invention relates to a biological base material and a manufacturing method thereof, in particular to a medical titanium base material and a manufacturing method thereof.

Background technique

When bio-substrate materials are implanted into living organisms, the surface of the substrate material will have very complex physiological interactions with biological tissues, and the physical and chemical properties of the surface of the bio-substrate material, such as surface morphology, roughness, and surface energy, can affect its biological properties. Chemical response (G. Mendonca, D. Mendonca, Biomaterials, 2008, 29:3822). Titanium and its alloys have the advantages of light weight, elastic modulus close to that of bone, good biocompatibility and corrosion resistance, and have become widely used hard tissue replacement substrate materials in the biomedical field. However, the surface of the titanium base material is biologically inert. After being implanted into the human body, a layer of fibrous wrapping tissue is often formed between the titanium base material and the bone tissue, which eventually leads to the failure of the implant and is difficult to meet the clinical biological activity requirements (X Liu, P.K.Chu, C.Ding, Mater. Sci. Eng. R, 2004, 47:49). Therefore, it is necessary to provide a titanium implant with high bioactivity and compatibility to reduce the differences in many properties between the titanium base material and the bone tissue.

Contents of the invention

In order to solve the problem of low bioactivity and compatibility on the surface of titanium base materials, the present invention provides a method for manufacturing medical titanium base materials, which includes the following steps in sequence:

surface pretreatment of the titanium base material, including a polishing step and a cleaning step;

Carry out acid etching treatment, the acid etching solution is volume ratio (1-3): 1 weight ratio of 48% sulfuric acid (H ₂ SO ₄ ) and weight ratio of 18% hydrochloric acid (HCl), the etching temperature is 65 -90°C, etching time is 1-3 hours, after acid etching treatment, a micron-scale pore structure is formed on the surface of the titanium base material;

For anodizing treatment, the electrolyte is 0.3%-1% ammonium fluoride (NH ₄ F) and 0.2%-1% hydrogen peroxide (H ₂ O ₂ ) ethylene glycol solution or 3 -10mol/L sodium hydroxide (NaOH) solution, the voltage is 10-50V, the temperature is room temperature, and the time is 30-180 minutes. After anodic oxidation treatment, a nano-scale titanium oxide pore structure is formed on the micro-scale pore structure, that is, the formation Micro/nano multi-level composite pore structure;

Carry out heat treatment at a temperature of 400-500°C for 2-4 hours. After heat treatment, an anatase titanium dioxide (TiO ₂ ) film layer with a micron/nano multilevel composite pore structure is formed on the surface of the titanium base material. The pore size of the micron/nano multi-level composite pore structure ranges from 10 nanometers to 6 microns.

In the surface pretreatment step, the titanium base material is polished to 1200# step by step with carbonized carbon water abrasive paper, and the titanium base material is cleaned by ultrasonic cleaning with acetone, ethanol and water in sequence, and then dried for later use.

After the acid etching step, the titanium metal substrate was removed for ultrasonic cleaning and allowed to dry for later use.

In the anodizing step, the electrolytic solution for anodic oxidation is acetone containing 0.3%-1% ammonium fluoride (NH ₄ F) and 0.2%-1% hydrogen peroxide (H ₂ O ₂ ) by weight. Diol solution to obtain a micro/nano multi-level sponge-like pore structure; the anodic oxidation electrolyte is 3-10mol/L sodium hydroxide (NaOH) solution to obtain a micro/nano multi-level network pore structure.

The heat treatment step is carried out in a muffle furnace to crystallize the amorphous titanium dioxide film after anodic oxidation into an anatase titanium dioxide film layer.

The medical titanium base material manufactured by the above method comprises a titanium base and an anatase titanium dioxide film layer with a micron/nano multilevel composite pore structure formed on the surface of the titanium base. The micron/nano multi-level composite pore structure is a micron/nano multi-level network pore structure or a micron/nano multi-level sponge-like pore structure. The pore size of the micron/nano multi-level composite pore structure ranges from 10 nanometers to 6 microns, and its surface structure makes it have high biological activity and biocompatibility. The above method for manufacturing medical titanium base material can be widely applied to the surface modification of metal implants.

Description of drawings

Fig. 1 is the SEM photograph of the titanium base material obtained in embodiment 1 and embodiment 2.

FIG. 2 is the Raman spectrum of the titanium base material obtained in Example 1 and Example 2.

Fig. 3 is the SEM photo of the titanium base material obtained in Example 1, Comparative Example 2 and Comparative Example 3.

Fig. 4 is a SEM photograph of MG63 cells cultured on the titanium substrate materials obtained in Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3 for 24 hours respectively.

Figure 5 shows the MTT absorbance values of MG63 cells cultured on the titanium base materials obtained in Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3 for 1 day, 3 days and 7 days respectively.

FIG. 6 is an SEM photo of the titanium base material obtained in Example 2 and Comparative Example 4.

FIG. 7 is a fluorescence image of MG63 cells cultured on the titanium substrate materials obtained in Example 2, Comparative Example 1, and Comparative Example 4 for 24 hours.

Fig. 8 shows the MTT absorbance values of MG63 cells cultured on the titanium substrate materials obtained in Example 2, Comparative Example 1 and Comparative Example 4 for 1 day, 3 days and 7 days respectively.

Fig. 9 is a SEM photo of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 soaked in SBF solution for 14 days.

Fig. 10 is the EDS analysis spectrum of the deposited film layer on the surface of the titanium base material obtained in Example 1 and Example 2.

Fig. 11 is an infrared analysis spectrogram of the deposit film layer on the surface of the titanium base material obtained in Example 1 and Example 2.

detailed description

Example 1:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

The acid-etched titanium plate was placed in an ethylene glycol electrolytic solution containing 0.3% NH ₄ F and 0.2% H ₂ O ₂ for electrochemical anodic oxidation treatment at a voltage of 50 V for 30 minutes. Rinse with water and then dry to form a nano-scale titanium oxide pore structure on the micro-scale pore structure, that is, form a micron/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium base material. The titanium dioxide film has a micro/nano multi-level sponge Pore structure. As shown in the SEM photos of Figure 1(a) and (b), the pore size range of the micro/nano hierarchical sponge-like pore structure is 10nm-6μm.

Example 2:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the pretreated titanium plate in the acid etching solution of 48% H2SO4 and 18% HCl with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out and ultrasonically clean it, and clean it on the surface of the titanium plate A micron-sized titanium pore structure is formed.

Put the acid-etched titanium plate in a 5mol/L NaOH electrolytic solution for electrochemical anodic oxidation treatment, the voltage is 15V, and the time is 120 minutes. After taking it out, rinse it with pure water and dry it to form a micron-scale pore structure. Nano-scale titanium oxide pore structure, that is, the formation of micro/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium substrate material. The titanium dioxide film has a micro/nano multi-level network Pore structure. As shown in the SEM photos of Figure 1(c) and (d), the pore size range of the micro/nano hierarchical network-like pore structure is 10nm-6μm.

In the Raman spectrum of Fig. 2, curve a corresponds to the titanium dioxide film with micron/nano hierarchical network-like pore structure in Example 1, and curve b corresponds to titanium dioxide with micron/nanometer multi-level network-like pore structure in Example 1 membrane. The characteristic spectral peaks of anatase TiO ₂ appeared at the wavelengths of Raman spectrum at 145cm ^-1 , 397cm ^-1 , 515cm ^-1 and 638cm ^-1 , thus confirming that in Examples 1 and 2, after heat treatment The main component of the surface film layer of the post-titanium base material is anatase TiO ₂ .

Example 3:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

The acid-etched titanium plate was placed in an ethylene glycol electrolytic solution containing 0.3% NH ₄ F and 0.2% H ₂ O ₂ for electrochemical anodic oxidation treatment at a voltage of 40V for 60 minutes. Rinse with water and then dry to form a nano-scale titanium oxide pore structure on the micro-scale pore structure, that is, form a micron/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium base material. The titanium dioxide film has micron/nano multi-level Sponge-like pore structure. The titanium dioxide film has a micro/nano multi-level sponge-like pore structure with a pore diameter ranging from 40 nm to 6 μm.

Example 4:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

Put the acid-etched titanium plate in 5mol/L NaOH electrolytic solution for electrochemical anodic oxidation treatment, the voltage is 10V, the time is 180 minutes, after taking it out, it is rinsed with pure water and then dried, forming on the micron-scale pore structure Nano-scale titanium oxide pore structure, that is, the formation of micro/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace, calcined at 450°C for 2 hours, and an anatase titanium dioxide film is formed on the surface of the titanium base material after heat treatment. The titanium dioxide film has a pore size ranging from 20nm to 6μm The micro/nano multi-level network-like pore structure.

Example 5:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

The acid-etched titanium plate was placed in an ethylene glycol electrolytic solution containing 0.3% NH ₄ F and 0.2% H ₂ O ₂ for electrochemical anodic oxidation treatment at a voltage of 35V for 30 minutes. Rinse with water and then dry to form a nano-scale titanium oxide pore structure on the micro-scale pore structure, that is, form a micron/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium base material. The titanium dioxide film has a micro/nano multi-level sponge Pore structure. The titanium dioxide film has a micron/nano multi-level sponge-like pore structure with a pore diameter ranging from 50 nm to 6 μm.

Embodiment 6:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the pretreated titanium plate in the acid etching solution of 48% H ₂ SO ₄ and 18% HCl with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

Put the acid-etched titanium plate in 3mol/L NaOH electrolytic solution for electrochemical anodic oxidation treatment, the voltage is 20V, and the time is 60 minutes. After taking it out, rinse it with pure water and dry it to form a micron-scale pore structure. Nano-scale titanium oxide pore structure, that is, the formation of micro/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace, calcined at 450°C for 2 hours, and an anatase titanium dioxide film is formed on the surface of the titanium base material after heat treatment. The titanium dioxide film has a pore size ranging from 30nm to 6μm The micro/nano multi-level network-like pore structure.

Embodiment 7:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

The acid-etched titanium plate was placed in an ethylene glycol electrolytic solution containing 1% NH ₄ F and 1% H ₂ O ₂ for electrochemical anodic oxidation treatment at a voltage of 50 V for 180 minutes. Rinse with water and then dry to form a nano-scale titanium oxide pore structure on the micro-scale pore structure, that is, form a micron/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium base material. The titanium dioxide film has a micro/nano multi-level sponge Pore structure. The titanium dioxide film has a micron/nano multi-level sponge-like pore structure with a pore diameter ranging from 30 nm to 6 μm.

Embodiment 8:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

Put the acid-etched titanium plate in 10mol/L NaOH electrolytic solution for electrochemical anodic oxidation treatment, the voltage is 15V, and the time is 120 minutes. After taking it out, rinse it with pure water and dry it to form a micron-scale pore structure. Nano-scale titanium oxide pore structure, that is, the formation of micro/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace, calcined at 450°C for 2 hours, and an anatase titanium dioxide film is formed on the surface of the titanium base material after heat treatment. The titanium dioxide film has a pore size ranging from 20nm to 6μm The micro/nano multi-level network-like pore structure.

Embodiment 9:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the pretreated titanium plate in the acid etching solution of 48% H ₂ SO ₄ and 18% HCl with a volume ratio of 2:1, etch at 85°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

Place the acid-etched titanium plate in an ethylene glycol electrolytic solution of 0.3% NH ₄ F and 0.2% H ₂ O ₂ for electrochemical anodic oxidation treatment, the voltage is 50V, and the time is 30 minutes. After taking it out, wash it with pure water After rinsing and drying, a nano-scale titanium oxide pore structure is formed on the micro-scale pore structure, that is, a micron/nano multi-level composite pore structure is formed.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium base material. The titanium dioxide film has a micro/nano multi-level sponge Pore structure. The titanium dioxide film has a micro/nano multi-level sponge-like pore structure with a pore diameter ranging from 20 nm to 5 μm.

Example 10:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the pretreated titanium plate in the acid etching solution of 48% H ₂ SO ₄ and 18% HCl with a volume ratio of 2:1, etch at 85°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale titanium pore structure is formed on the surface of the titanium plate.

Put the acid-etched titanium plate in a 5mol/L NaOH electrolytic solution for electrochemical anodic oxidation treatment, the voltage is 15V, and the time is 180 minutes. After taking it out, rinse it with pure water and dry it to form a micron-scale pore structure. Nano-scale titanium oxide pore structure, that is, the formation of micro/nano multi-level composite pore structure.

The anodized titanium plate is placed in a muffle furnace, calcined at 450°C for 2 hours, and an anatase titanium dioxide film is formed on the surface of the titanium base material after heat treatment. The titanium dioxide film has a pore size ranging from 15nm to 5μm The micro/nano multi-level network-like pore structure.

Comparative example 1:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use. the

Comparative example 2:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 48% H ₂ SO ₄ and 18% HCl acid etching solution with a volume ratio of 2:1, etch at 75°C for 1 hour, take it out, and ultrasonically clean it. A micron-scale pore structure is formed on the surface of the titanium plate.

The acid-etched titanium plate was placed in a muffle furnace and calcined at 450°C for 2 hours.

Comparative example 3:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Place the pretreated titanium plate in an ethylene glycol electrolytic solution containing 0.3% NH ₄ F and 0.2% H ₂ O ₂ for electrochemical anodizing treatment at a voltage of 50V for 30 minutes. Rinse with water and then dry to form a nanoscale pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium substrate material. The titanium dioxide film has a nanoscale sponge-like pore structure .

Comparative example 4:

Take a pure titanium plate with a size of 10mm×10mm×2mm, grind and polish it step by step to 1200# with carbonized carbon water abrasive paper, clean it with acetone, ethanol and water in sequence, and dry it for later use.

Put the surface-pretreated titanium plate in 5mol/L NaOH electrolytic solution for electrochemical anodic oxidation treatment, the voltage is 15V, the time is 120 minutes, after taking it out, rinse it with pure water and dry it to form a nano-scale pore structure.

The anodized titanium plate is placed in a muffle furnace and calcined at 450°C for 2 hours. After heat treatment, an anatase titanium dioxide film is formed on the surface of the titanium substrate material. The titanium dioxide film has a nanoscale network-like pore structure .

Contrast of embodiment 1 and comparative examples 1 to 3:

Figure 3 is the SEM photos of Example 1, Comparative Example 2 and Comparative Example 3, where (a ₁ ), (a ₂ ), (a ₃ ) correspond to the SEM photos of Comparative Example 2, (b ₁ ), (b ₂ ), (b ₃ ) correspond to the SEM photos of Comparative Example 3, and (c ₁ ), (c ₂ ), (c ₃ ) correspond to the SEM photos of Example 1. Fig. 4 is a SEM photograph of MG63 cells cultured on the titanium substrate materials obtained in Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3 for 24 hours respectively. Among them, (a ₁ ), (a ₂ ) correspond to the SEM photos of Comparative Example 1, (b ₁ ), (b ₂ ) correspond to the SEM photos of Comparative Example 2, and (c ₁ ), (c ₂ ) correspond to the SEM photos of Comparative Example 2. The SEM photographs of Example 3, (d ₁ ) and (d ₂ ) correspond to the SEM photographs of Example 1. MG63 cells showed a fusiform shape on the surface of the pure titanium plate, and the pseudopodia of the cells were not obviously stretched, and they were not completely spread out. On the surface of the titanium base material obtained in Comparative Example 2, Comparative Example 3, and Example 1, the cells grew relatively stretched, showing the extension of multiple pseudopodia, and the cells adhered better on the surface of the material.

Figure 5 shows the MTT absorbance values (OD) of MG63 cells cultured on the titanium substrate materials obtained in Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3 for 1 day, 3 days and 7 days respectively. It can be seen from the figure that after one day of culture, the number of MG63 cells on the titanium base material obtained in Example 1 and Comparative Example 3 is slightly more than that on the titanium base material obtained in Comparative Example 1 and Comparative Example 2. After cultivating for 3 days, the number of cells on the surface of Example 1, Comparative Example 2 and Comparative Example 3 was more than that on the surface of Comparative Example 1, but there was no significant difference between the number of cells on the surface of Comparative Example 3 and the number of cells on the surface of Example 1, so After 3 days of culture, the number of cells on the surface of different materials showed the following rules: Example 1≈Comparative Example 3>Comparative Example 2>Comparative Example 1. After continuing to culture for 7 days, the growth conditions on the surface of the cells in Example 1, Comparative Example 2 and Comparative Example 3 were all better than those on the surface of Comparative Example 1, and the number of cells on the surface of Example 1 was the largest, and the number of cells on the surface of different materials was as follows Relationship: Example 1>Comparative Example 3>Comparative Example 2>Comparative Example 1.

Table 1 is the water droplet contact angle values of Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3.

Table 1

Comparative example 1 Comparative example 2 Comparative example 3 Example 1 52.6±1.26 26.2±1.63 5.5±1.13 1.2±0.87

It can be seen from Table 1 that the surface water droplet contact angle of the titanium base material obtained in Example 1 is less than 5, indicating that its surface is super-hydrophilic. According to the surface wettability theory proposed by Wenzel and Cassie et al., if it is a hydrophilic sample, the surface of the sample will be more hydrophilic after increasing the roughness; conversely, if it is a hydrophobic sample, the surface of the sample will be more hydrophobic after increasing the roughness. The above surface wettability test results are consistent with this theory, indicating that this is caused by factors such as surface morphology and roughness. The surface of the titanium base material obtained in Example 1 has strong hydrophilicity, which is beneficial to the adhesion and growth of cells on the surface, so the surface has the highest biological activity. the

The contrast of embodiment 2 and comparative example 4:

FIG. 6 is the SEM photos of Example 2 and Comparative Example 4, where (a1) and (a2) correspond to Comparative Example 4, and (b1) and (b2) correspond to Example 2. It can be seen that the surface of the titanium base material obtained in Comparative Example 4 has a network crosslinked structure with a pore size of about 10 to 100 nm, while the surface of the titanium base material obtained in Example 2 has microscopic crosslinking structures. / Nano-hierarchical porous structure, that is, a nano-scale network-like structure appears under the condition of not affecting the micro-porous structure.

FIG. 7 is a fluorescence image of MG63 cells cultured on the titanium base materials obtained in Example 2, Comparative Example 1, and Comparative Example 4 for 1 day. Among them, (a1) and (a2) correspond to Comparative Example 1, (b1) and (b2) correspond to Comparative Example 4, and (c1) and (c2) correspond to Example 2. It can be seen that the MG63 cells could not spread well on the surface of Comparative Example 1, showing a certain spindle shape. On the surface of Example 2 and Comparative Example 4 after the modification treatment, the cells showed a star-shaped spread, and the stretching state was good, but the cell attachment state on the surface of the titanium base material obtained in Example 2 and Comparative Example 4 Not much difference.

Figure 8 shows the MTT absorbance values (OD) of MG63 cells cultured on the titanium base materials obtained in Example 2, Comparative Example 1 and Comparative Example 4 for 1 day, 3 days and 7 days respectively. It can be seen from the figure that with the prolongation of time, the number of cells on the surface of each titanium substrate material is gradually increasing. After cultivating for 1 day, the number of cells on the surface of each titanium base material was not much different, and there was not much difference; after culturing for 3 days, the number of cells on the surface of Example 2 and Comparative Example 4 was more than that of Comparative Example 1, while that of Example 2 and Comparative Example 1 was different. There is no significant difference in the number of cells on the surface of Comparative Example 4; after culturing for 7 days, the titanium base material obtained in Example 2 has the largest number of cells on the surface, and the number of cells on the surface of the titanium base material obtained in Comparative Example 4 is the second. Based on the above results, it can be found that in terms of promoting cell proliferation, the biological activity of the material is as follows: Example 2>Comparative Example 4>Comparative Example 1.

Table 2 is the water drop contact angle values of Example 2 and Comparative Example 4.

Table 2

Comparative example 4 Example 2 9.8±1.37 1.8±1.02

It can be seen from Table 2 that the surface water droplet contact angle of the titanium base material obtained in Example 2 is less than 5, indicating that its surface is super-hydrophilic. The surface of the titanium base material obtained in Example 2 is highly hydrophilic, which is beneficial to the adhesion and growth of cells on the surface, so the surface has the highest biological activity.

The contrast of embodiment 1-2 and comparative example 1-2:

In order to test the biological activity of the titanium base materials after different treatments, the titanium base materials obtained in Example 1, Example 2, Comparative Example 1, and Comparative Example 2 were soaked in SBF solution at 36.5° C. for 14 days.

Figure 9 is the SEM photos of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 soaked in SBF solution for 14 days, where (a) corresponds to Example 1, (b) corresponds to Example 2, (c ) corresponds to Comparative Example 1, and (d) corresponds to Comparative Example 2. The surface of the titanium base material obtained in Examples 1 and 2 forms a layer of deposits, the original surface morphology of the titanium base material is completely covered, and the film layer of the deposit is a hemispherical pore structure assembled by nano-flaky crystals , showing a typical apatite morphology, indicating that the titanium substrate material with a titanium dioxide film layer of a micro/nano composite structure has significantly enhanced biological activity. However, no apatite film was found on the surface of the titanium base materials obtained in Comparative Example 1 and Comparative Example 2, and their biological activity was poor.

FIG. 10 is an EDS analysis spectrum of the deposited film layer on the surface of the titanium base material obtained in Example 1 and Example 2. The results show that the film layer is mainly composed of Ca, P and O elements, and the ratio of calcium to phosphorus is about 1.34, which is a calcium-deficient apatite. In addition, it also contains C and Mg elements, which are close to the apatite composition in natural bone.

FIG. 11 is an infrared spectrum analysis spectrum of the deposit film layer on the surface of the titanium base material obtained in Example 1 and Example 2. The symmetrical stretching vibration of PO ₄ ^3- (ν ₃ ) appeared at 1038cm ^-1 , and the bending vibration of O—P—O (ν ₄ ) appeared at 602cm ^-1 and 561cm ^-1 . The absorption peaks of CO ₃ ^2- appeared at 1460cm ^-1 , 1420cm ^-1 and 875cm ^-1 , indicating that the apatite formed after soaking SBF contained CO ₃ ^2- , and CO ₃ ^2- partially replaced PO ₄ ^3- . In summary, the apatite layer formed on the surface of the titanium base material is apatite in which calcium-deficient carbonate partially replaces phosphate, and also contains magnesium and carbon elements. This composition is similar to that of apatite in natural bone. Very similar, known as bone-like apatite.

In summary, although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention, and those skilled in the art should realize that the scope of the present invention disclosed in the appended claims of the present invention The changes and modifications made under the conditions of the spirit and the spirit all belong to the protection scope of the claims of the present invention.

Claims (4)

1. a medical titanium substrate material, is characterized in that, is made up of the anatase titanium dioxide rete of the micrometer/nanometer multistage composite pore structure formed at the bottom of titanio and on this titanio basal surface; Wherein, described micrometer/nanometer multistage composite pore structure is micrometer/nanometer multistage network shape pore structure or the multistage spongy pore structure of micrometer/nanometer;

The preparation of described medical titanium substrate material comprises the following steps successively:

Carry out surface preparation at the bottom of titanio, comprise polishing and cleaning;

Carry out acid etch process, acid etch solution is sulphuric acid and hydrochloric acid mixed solution, micrometer grade hole structure is formed at described titanio basal surface after acid etch process, the weight ratio of described acid etch solution to be volume ratio be A:1 is 48% sulfuric acid solution and weight ratio is 18% hydrochloric acid solution mixing, etching temperature is 65-90 DEG C, etch period is 1-3 hour, wherein 1≤A≤3;

Carry out anodized, after anodized, micron scale construction forms nano grade pore structure, namely form micrometer/nanometer multistage composite pore structure;

Heat-treat, at the anatase titanium dioxide rete of the micrometer/nanometer multistage composite pore structure of titanium substrate material surface formation after Overheating Treatment;

When described anodised electrolyte is that when be the ammonium fluoride of 0.3%-1% and weight ratio being the ethylene glycol solution of 0.2%-1% hydrogen peroxide containing weight ratio, the micrometer/nanometer multistage composite pore structure obtained is the multistage spongy pore structure of micrometer/nanometer;

When described anodised electrolyte be concentration is the sodium hydroxide solution of 3-10mol/L, the micrometer/nanometer multistage composite pore structure obtained is micrometer/nanometer multistage network shape pore structure.

2. medical titanium substrate material as claimed in claim 1, it is characterized in that, the pore diameter range of micrometer/nanometer multistage composite pore structure is 10 nanometers to 6 micron.

3. medical titanium substrate material as claimed in claim 1, it is characterized in that, described anodised voltage is 10-50V, and temperature is room temperature, and the time is 30-180 minute.

4. medical titanium substrate material as claimed in claim 1, it is characterized in that, the temperature of described heat treatment step is 400-500 DEG C, and the time is 2-4 hour.