A method for preparing a high-efficiency piezoelectric coating on a titanium implant surface

Abstract

The application provides a preparation method of a high-efficiency piezoelectric coating on a titanium implant surface. The preparation method of the application uses a hydrothermal treatment and an in-situ piezoelectric deposition technology to in-situ synthesize a nano strontium titanate-noble metal piezoelectric coating on the titanium implant surface. The coating can generate a piezoelectric potential and active oxygen through ultrasonic driving to degrade extracellular polymers and kill bacteria. In addition, the piezoelectric coating can also promote the osteogenic differentiation of bone marrow mesenchymal stem cells under piezoelectric stimulation, and finally realize the effects of bioactivity, long-acting drug-resistant bacteria and high-efficiency bone integration in the body. The application can provide a new surface treatment technology and research idea for controlling the drug-resistant bacteria infection on the implant surface, help to break through the limitations of the existing theory and technology in removing bacterial infection on the titanium implant surface, and provide beneficial guidance for the control of bacterial biofilm on other parts and the prevention and treatment of related infectious diseases.

Description

TECHNICAL FIELD

[0001] The application relates to a preparation method of a high-efficiency piezoelectric coating on a titanium implant surface, in particular to a preparation method of constructing a nano strontium titanate-noble metal piezoelectric coating on a titanium metal surface, and belongs to the technical field of medical implant materials. BACKGROUND

[0002] Titanium and titanium alloys have been widely used in dental and orthopedic clinics due to their excellent mechanical strength, chemical stability and corrosion resistance. However, titanium implants do not have sterilization and antibacterial activity, and the requirement for their bone bonding capacity is also relatively high. Killing bacteria through material surface modification can effectively eliminate drug-resistant bacterial infection and promote the firm combination of implants and host bone formation, which is of great significance for preventing and treating implant infection and avoiding implant replacement. The root cause of implant bacterial infection is that bacteria adhere to the implant surface before cells, forming a biofilm and causing surrounding tissue necrosis. Generally, loading bactericidal drugs in a bioactive coating is an effective solution to achieve local anti-infection and avoid systemic use of antibiotics. Antibiotics, inorganic ions (silver, copper, zinc, etc.) and organic bactericides (quaternary ammonium salt, chitosan, antibacterial peptide, etc.) are widely loaded on the surface of implants; however, they usually have dose-dependent antibacterial activity, more or less cytotoxicity, or have specificity or side effects (such as the generation of drug-resistant bacteria).

[0003] Studies have shown that collagen, mucopolysaccharide and other substances in bone matrix are piezoelectric materials, which can generate electric signals under mechanical force stimulation and provide electric stimulation to surrounding cells. The electric field formed by the potential change of the damaged position of bone tissue can promote cell migration, proliferation and differentiation, and promote tissue repair. Under piezoelectric stimulation, the osteogenic differentiation of bone marrow mesenchymal stem cells can also be promoted, and finally the effects of bioactivity, long-acting anti-drug-resistant bacteria and high-efficiency bone integration can be achieved in vivo. Therefore, the piezoelectric coating can generate piezoelectric potential and generate active oxygen to kill bacteria and degrade biofilm extracellular polymers through ultrasonic driving, which can achieve the purpose of clearing bacterial infection.

[0004] At present, researchers at home and abroad mainly use spin coating, electrochemical method, sol-gel method, hydrothermal method and anodic oxidation method to prepare piezoelectric coatings on the surface of titanium. The binding strength between the coating and the substrate material prepared by these methods is low, and the piezoelectric performance of the coating is also low. There are also studies on the preparation of piezoelectric coatings by micro-arc oxidation method, but this method has high energy consumption and high cost, and it is difficult to produce large-area test pieces. On the other hand, the existing piezoelectric coatings are mainly barium titanate and lithium niobate, which have poor biocompatibility and are not suitable for implant surface modification. In addition, some researchers have prepared strontium-doped coatings on the surface of titanium, but the coatings obtained in these studies are strontium-doped titanium dioxide or amorphous strontium titanate, which do not have piezoelectric properties. Therefore, the present application is proposed. SUMMARY

[0005] In view of the deficiencies of the prior art, the present application provides a preparation method of a titanium implant surface high-efficiency piezoelectric coating. The present application combines the use of hydrothermal treatment and in-situ piezoelectric deposition technologies to synthesize a nano-strontium titanate-noble metal piezoelectric coating on the surface of a titanium implant in-situ. The coating can generate piezoelectric potential and active oxygen through ultrasonic driving to degrade extracellular polymers and kill bacteria. In addition, the piezoelectric stimulation can also promote the osteogenic differentiation of mesenchymal stem cells, and ultimately achieve the effects of bioactivity, long-acting drug-resistant bacteria and high-efficiency bone integration in the body. The present application can provide new surface treatment technologies and research ideas for controlling the infection of drug-resistant bacteria on the surface of the implant, which helps to break through the limitations of existing theories and technologies in removing bacterial infection on the surface of the titanium implant, and also provides beneficial guidance for the control of bacterial biofilm on other parts and the prevention and treatment of related infectious diseases.

[0006] The technical scheme of the present application is as follows:

[0007] A preparation method of a titanium implant surface high-efficiency piezoelectric coating, comprising the following steps:

[0008] (1) The pretreated titanium implant is immersed in an alkaline solution for treatment, washed and dried, and then added into an Sr(OH)2 aqueous solution for hydrothermal reaction. After the reaction is completed, the titanium implant surface is formed with a strontium titanate coating after washing and drying, and a titanium implant with a strontium titanate coating (Ti-SrTiO3) is obtained;

[0009] (2) The titanium implant with the strontium titanate coating obtained in step (1) is placed in a (3-mercaptopropyl) trimethoxysilane ethanol solution, and then ultrasonic treatment is performed. After washing and drying, a titanium implant with a mercapto-piezoelectric coating is obtained;

[0010] (3) The titanium implant with the mercapto-piezoelectric coating is placed in a metal salt solution, and then methanol aqueous solution is added. After adjusting the pH of the mixture, ultrasonic treatment is performed. After washing and drying, a high-efficiency piezoelectric coating is obtained on the surface of the titanium implant.

[0011] According to the present application, the shape of the titanium implant in step (1) is a nail, a plate, a mesh, a disc or a column; and the titanium implant is a commercial pure titanium implant.

[0012] According to the present application, preferably, the pretreatment step in step (1) is that the titanium implant is sequentially washed with acetone, ethanol and deionized water, and then air-dried for standby.

[0013] According to the present application, preferably, the alkaline solution in step (1) is a sodium hydroxide solution with a concentration of 1-10 mol / L.

[0014] According to the application, preferably, the temperature for treating the titanium implant in step (1) is 50-70℃, and the treatment time is 0.5-24h; and the titanium implant is completely immersed in the alkaline solution.

[0015] According to the application, preferably, the concentration of the Sr(OH)2 aqueous solution in step (1) is 0.01-1mol / L; and the titanium implant treated by the alkaline solution is completely immersed in the Sr(OH)2 aqueous solution.

[0016] According to the application, preferably, the temperature for the hydrothermal reaction in step (1) is 220-260℃; and the time for the hydrothermal reaction is 2-48h.

[0017] According to the application, preferably, the washing in step (1) is all by deionized water; and the drying is all by natural air drying.

[0018] According to the application, preferably, the volume concentration of the (3-mercaptopropyl)trimethoxysilane ethanol solution in step (2) is 0.1-10%(v / v); and the titanium implant with strontium titanate coating is completely immersed in the (3-mercaptopropyl)trimethoxysilane ethanol solution.

[0019] According to the application, preferably, the time for the ultrasonic treatment in step (2) is 10-60 minutes, and further preferably 30-60 minutes; the washing is by sequentially using toluene, ethanol, deionized water and acetone for 5-10 minutes each; and the drying is by nitrogen drying at room temperature for 10-15h, wherein the room temperature refers to 25±5℃.

[0020] According to the application, preferably, the metal salt in step (3) is HAuCl4, AgNO3, K2PtCl4 or Na2PdCl4; and the concentration of the metal salt solution is 1-50mmol / L, and further preferably 5-15mmol / L.

[0021] According to the application, preferably, the volume concentration of the methanol aqueous solution in step (3) is 5-50%(v / v), and further preferably 10-30%(v / v); and the volume ratio of the methanol aqueous solution to the metal salt solution is 1:1. The titanium implant with mercapto-piezoelectric coating is completely immersed in the mixture of the metal salt solution and the methanol aqueous solution.

[0022] According to the application, preferably, the pH of the mixture in step (3) is adjusted to 9-11 by using K2CO3 solution, and further preferably 9.5-10; and the concentration of the K2CO3 solution is 0.1-5mol / L.

[0023] According to the application, preferably, the vibration frequency of the ultrasonic treatment in step (3) is 40 kHz, the power is 80 W, the ultrasonic treatment time is 2-120 min, further preferably 30-90 min, and the ultrasonic treatment temperature is 0-60 DEG C, further preferably 4-10 DEG C.

[0024] According to the application, preferably, the washing in step (3) is washing 3-5 times with deionized water, and the drying is drying overnight at room temperature with nitrogen.

[0025] The application further provides a titanium implant with a high-efficiency piezoelectric coating on the surface, which is prepared by the above method.

[0026] According to the application, the titanium implant with a high-efficiency piezoelectric coating on the surface is used in the preparation of an orthopedic implant.

[0027] The technical features and advantages of the application are as follows:

[0028] 1. The application forms a SrTiO3 piezoelectric coating on the surface of a titanium alloy in situ by alkali heating assisted by hydrothermal treatment, then deposits noble metal nanoparticles on the surface of the titanium alloy in situ by piezoelectric catalysis to form a SrTiO3-noble metal coating, so as to promote the separation of electron holes and achieve the effect of high-efficiency resistance to drug-resistant bacteria, and the application innovates the construction method of the coating on the surface of a titanium alloy.

[0029] 2. The SrTiO3-noble metal coating prepared by the application can generate a piezoelectric potential and active oxygen under the ultrasonic piezoelectric driving, which can degrade extracellular polymers and kill bacteria on the one hand, and the electric stimulation can also promote the osteogenic differentiation of mesenchymal stem cells, realizing high-efficiency bone integration of the implant.

[0030] 3. The application designs and obtains a SrTiO3-noble metal coating on the surface of a titanium alloy that responds to ultrasonic waves; regulates the piezoelectric potential and the yield of active oxygen groups under ultrasonic driving, activates the host immune system through piezoelectric stimulation to enhance the antibacterial property, and realizes the effect of enhancing the immune regulation of macrophages to resist drug-resistant bacteria and osteogenesis.

[0031] 4. The nano-strontium titanate-noble metal piezoelectric coating synthesized using the process of this invention exhibits high bonding strength with titanium and its alloy substrates, high coating stability, high biocompatibility of strontium ions, significant osteogenic effect, low precipitation amount, and no cytotoxicity, meeting the requirements for clinical applications. Compared with titanium and its alloys, this coating has good biocompatibility, a porous structure that facilitates the adhesion, proliferation, and differentiation of osteocytes, and ferroelectric properties. Polarization treatment can impart surface charge, giving the material osteoinductive properties, promoting new bone formation, promoting the integration of implants with bone, and promoting fracture healing. Simultaneously, this coating can also respond to external ultrasonic mechanical stimulation, generating active oxygen groups through external ultrasound to kill pathogenic bacteria on the surface, thereby achieving antibacterial effects. Attached Figure Description

[0032] Figure 1 SEM image (a) and XRD image (b) of the SrTiO3-Au coating prepared in Example 1.

[0033] Figure 2 Hysteresis loop and butterfly curve of SrTiO3-Au piezoelectric coating prepared in Example 1.

[0034] Figure 3 The SrTiO3-Au coating prepared for Example 1 was at 1 W / cm 2 Yield of reactive oxygen species under ultrasonic power.

[0035] Figure 4 The SrTiO3-Au coating prepared for Example 1 was tested at 0 and 1 W / cm². 2 Antibacterial properties under ultrasonic power. Detailed Implementation

[0036] The present invention will be further described below with reference to specific embodiments and accompanying drawings. These embodiments are provided to enable those skilled in the art to better understand the invention and are not intended to limit the scope of the invention in any way.

[0037] In addition, the experimental methods described in the following embodiments are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0038] The titanium implant used in this embodiment is in the shape of a titanium sheet, and its size is...

[0039] Example 1

[0040] A method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant includes the following steps:

[0041] (1) The titanium implant was sequentially washed with acetone, ethanol and deionized water under ultrasonic and air dried, and then placed in a 10 mol / L NaOH solution, treated at 60°C for 4 h; washed with deionized water and air dried, and then placed in a reaction kettle, and then 30 mL of 0.5 mol / L Sr(OH)2 aqueous solution was added to the reaction kettle, and hydrothermal reaction was carried out at 240°C for 12 h; after the reaction was completed, the titanium implant was washed with deionized water and air dried, and a strontium titanate piezoelectric coating was formed on the surface of the titanium implant, and a titanium implant with a strontium titanate coating (SrTiO3-Ti) was obtained.

[0042] (2) The titanium implant with a strontium titanate coating obtained in step (1) was placed in 10 mL of a (3-mercaptopropyl)trimethoxysilane ethanol solution with a volume concentration of 10% (v / v), and then ultrasonic treatment was carried out for 30 min; the titanium implant was sequentially washed with toluene, ethanol, deionized water and acetone for 10 min each time, and then dried with nitrogen at room temperature for 12 h, to obtain a titanium implant with a mercapto piezoelectric coating.

[0043] (3) The dried titanium implant with a mercapto piezoelectric coating was placed in 10 mL of a 10 mmol / L HAuCl4 solution, and then 10 mL of a methanol aqueous solution with a volume concentration of 10% (v / v) was added; after the pH of the mixture was adjusted to 9.7 using a 0.5 mol / L K2CO3 solution, the mixture was treated with ultrasonic vibration at 4°C, the vibration frequency was 40 kHz, the power was 80 W, and the ultrasonic treatment time was 60 min; then the titanium implant was washed with deionized water for 3 times, and dried with nitrogen at room temperature overnight, to obtain a nano SrTiO3-Au coating on the surface of the titanium implant, i.e. a high-efficiency piezoelectric coating, denoted as SrTiO3-Au.

[0044] The SEM and XRD of the nano strontium titanate-gold piezoelectric coating (SrTiO3-Au) prepared in this example are shown in Figure 1 , which shows that the SrTiO3-Au coating is successfully constructed on the surface of the titanium alloy.

[0045] The electric hysteresis loop and butterfly curve of the nano strontium titanate-gold piezoelectric coating (SrTiO3-Au) prepared in this example are shown in Figure 2 , which proves that the obtained SrTiO3-Au coating has piezoelectric properties.

[0046] DCFH-DA fluorescent probe was used as the ROS action substrate, and a fluorescence spectrometer was used to quantitatively analyze the yield of ROS. As shown in Figure 3 , the yield of active oxygen groups of the SrTiO3-Au piezoelectric coating under ultrasonic driving at 1 W / cm 2 is much higher than that of pure titanium, which proves that the obtained SrTiO3-Au piezoelectric coating has piezoelectric catalytic activity.

[0047] Staphylococcus aureus was inoculated on the surface of each sample, treated by the ultrasonic physiotherapy instrument and incubated for a certain time, and the number of living bacteria on the surface of the sample was counted by plate counting. The antibacterial performance of the nano-strontium titanate-gold piezoelectric coating (SrTiO3-Au) prepared in this example on the Staphylococcus aureus on its surface was as shown in Figure 4 It can be seen from Figure 4 that the ultrasonic driven SrTiO3-Au surface has a strong killing ability on Staphylococcus aureus compared with pure titanium.

[0048] Example 2

[0049] A method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant is as described in Example 1, except that in step (3), the dried titanium implant with a mercaptoized piezoelectric coating is placed in 10 mL of a K2PtCl4 solution with a concentration of 10 mmol / L, and a nano-SrTiO3-Pt coating is obtained on the surface of the titanium implant, which is a high-efficiency piezoelectric coating and is denoted as SrTiO3-Pt.

[0050] The nano-strontium titanate-platinum piezoelectric coating (SrTiO3-Pt) prepared in this example has good ferroelectric / piezoelectric properties and piezoelectric catalytic properties. Compared with pure titanium, the ultrasonic driven SrTiO3-Pt surface has a strong killing ability on bacteria.

Claims

1. A method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant, comprising the following steps: (1) immersing a pretreated titanium implant into an alkaline solution for treatment, washing and drying, and then adding an aqueous Sr(OH) 2 solution for hydrothermal reaction; after the reaction, washing, drying, and forming a strontium titanate coating on the surface of the titanium implant, a titanium implant with a strontium titanate coating is obtained; the alkaline solution is a sodium hydroxide solution with a concentration of 10 mol / L; the temperature for immersing the titanium implant into the alkaline solution for treatment is 60℃, and the treatment time is 4 h; the concentration of the aqueous Sr(OH) 2 solution is 0.5-1 mol / L; the temperature for the hydrothermal reaction is 240-260℃; and the time for the hydrothermal reaction is 12-48 h; (2) placing the titanium implant with a strontium titanate coating obtained in step (1) into an (3-mercaptopropyl) trimethoxysilane ethanol solution, and then ultrasonic treatment, washing, and drying to obtain a titanium implant with a mercapto-functionalized piezoelectric coating; the volume concentration of the (3-mercaptopropyl) trimethoxysilane ethanol solution is 10%; (3) placing the titanium implant with a mercapto-functionalized piezoelectric coating into a metal salt solution, then adding an aqueous methanol solution, adjusting the pH of the mixture, and then ultrasonic treatment, washing, and drying to obtain a high-efficiency piezoelectric coating on the surface of the titanium implant; the metal salt is HAuCl 4; the concentration of the metal salt solution is 10 mmol / L; the volume concentration of the aqueous methanol solution is 10%; the volume ratio of the aqueous methanol solution to the metal salt solution is 1:1; the pH of the mixture is adjusted to 9.7 using a K 2 CO 3 solution; the vibration frequency of the ultrasonic treatment is 40 kHz, the power is 80 W, the ultrasonic treatment time is 60 min, and the ultrasonic treatment temperature is 4-10℃.

2. The method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant according to claim 1, characterized in that, In step (1), the pretreatment step is: washing the titanium implant with acetone, ethanol, and deionized water in sequence, and then air-drying for standby.

3. The method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant according to claim 1, characterized in that, In step (1), the washing is all with deionized water; and the drying is all natural air-drying.

4. The method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant according to claim 1, characterized in that, In step (2), the ultrasonic treatment time is 10-60 min; the washing is washing with toluene, ethanol, deionized water, and acetone in sequence for 5-10 min each time; and the drying is nitrogen drying at room temperature for 10-15 h.

5. The method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant according to claim 1, characterized in that, In step (3), the concentration of the K 2 CO 3 solution is 0.1-5 mol / L.

6. The method for preparing a high-efficiency piezoelectric coating on the surface of a titanium implant according to claim 1, characterized in that, In step (3), the washing is washing with deionized water for 3-5 times; and the drying is nitrogen drying at room temperature overnight.

7. A titanium implant having a high efficiency piezoelectric coating on its surface, characterized in that, The high-efficiency piezoelectric coating is prepared by the method of claim 1. 8.Use of the titanium implant with a high-efficiency piezoelectric coating on the surface of claim 7 in the preparation of an orthopedic implant.

Images