A method for surface antibacterial functionalization of a medical titanium alloy material

Abstract

The application discloses a kind of medical titanium alloy material surface antibacterial functionalization processing methods, first by hydrothermal oxidation and high-temperature sintering processing in titanium alloy material surface construction TiO2 Nanometer sheet, then deposit W 18 O 49 Quantum dots are deposited on the TiO2 Nanometer sheet, and TiO2 / W 18 O 49 Heterojunction is constructed on the surface of titanium alloy.TiO2 / W 18 O 49 Heterojunction can efficiently catalyze the production of reactive oxygen species (ROS) under near-infrared light irradiation, achieving antibacterial function. The TiO2 / W 18 O 49 Heterojunction functionalized titanium alloy material surface, the irregular sheet structure of TiO2 Nanometer sheet can greatly increase the contact area of the material surface and the surrounding solution, and the W 18 O 49 Quantum dots have the characteristics of "single-atom-like catalysis", which can improve the ROS yield and further endow the medical titanium alloy surface with strong photodynamic antibacterial performance.

Description

Technical Field

[0001] This invention relates to a method for surface antibacterial functionalization of medical titanium alloy materials, specifically involving the construction of TiO2 nanosheets and deposition of W on the surface of medical titanium alloys. 18 O 49 Quantum dot construction of TiO2 / W 18 O 49 Heterojunctions generate antibacterial effects through photodynamics. Background Technology

[0002] Titanium-based implants are increasingly used in the treatment of bone injuries and orthopedic diseases. However, the phagocytic function of macrophages near the implant is weakened, and the biofilm formed at the implant-tissue interface provides a favorable environment for bacterial growth, significantly increasing the risk of in vivo bacterial infection. According to statistics from the World Health Organization (WHO), bacterial infection causes approximately 4%-6% of medical device failures annually, affecting tens of millions of patients. As a common postoperative complication, bacterial growth on the implant surface can not only trigger local inflammatory reactions but also lead to implant dysfunction, and in severe cases, even endanger the patient's life.

[0003] While current methods allow for rigorous disinfection and sterilization of implants, and ensure relatively sterile surgical procedures to prevent bacterial introduction during implantation, postoperative bacterial infection cannot be completely eliminated. Studies show that most orthopedic implant-related infections are caused by opportunistic pathogens and bacteria commonly found in the human skin microbiome. Staphylococci, in particular, play a crucial role in the occurrence and development of postoperative infections. Literature reports that Staphylococcus aureus and various coagulase-negative staphylococci (such as Staphylococcus epidermidis) account for over 50% of fracture fixation device (FFD)-related infections and over 65% of prosthetic joint infections (PJIs). Therefore, many clinical practice guidelines recommend that physicians administer intravenous antibiotics preoperatively to reduce the risk of postoperative bacterial infection. Furthermore, while ensuring the sterility of the implant, postoperative antimicrobial function is also considered an indispensable and important characteristic of orthopedic implants.

[0004] The present invention aims to empower the surface of medical titanium alloys by surface functionalization, thereby giving them photodynamic antibacterial properties, which can prevent bacterial infection after implantation surgery. Summary of the Invention

[0005] The purpose of this invention is to provide a method for constructing TiO2 nanosheets / W on the surface of medical titanium alloy. 18 O 49 The method of quantum dot heterojunction; the second objective of the present invention is to provide a method for achieving photodynamic antibacterial function using the above-mentioned surface structure.

[0006] The medical titanium alloy surface described in this invention is composed of TiO2 nanosheets / W 18 O 49 The quantum dot heterostructure is formed; the surface of the medical titanium alloy described herein possesses photodynamic antibacterial properties. The W... 18 O 49 The size is as small as 2~4nm, and it is uniformly distributed on TiO2 nanosheets.

[0007] The above-mentioned method for surface antibacterial functionalization of medical titanium alloy materials includes the following steps: (1) The titanium alloy material was immersed in acetone, ethanol and deionized water in sequence, and ultrasonic cleaning was performed simultaneously; (2) Immerse the cleaned titanium alloy material in a certain proportion of KMnO4 and NaOH mixed solution, place it in a hydrothermal reaction vessel and heat it for a certain time, then rinse it with deionized water and dry it. (3) The titanium alloy material after the above treatment is sintered at high temperature for a certain time; (4) Add WCl6 and citric acid to the ethylene glycol / ethanol mixture. After it is fully dissolved, immerse the above titanium alloy material in it. Heat it in an oil bath under nitrogen atmosphere for a certain time, then let it cool naturally. Add sodium hydroxide solution and react for a certain time. Rinse with deionized water and dry.

[0008] Preferably, in step (2), the ratio of titanium alloy surface area, KMnO4, and NaOH is (1 mm²) / (1 mm²) = 1 mm² ... 2 ): (0.1~5mmol): (0.1~5mmol).

[0009] In step (2), the temperature of the heat treatment is 150~220℃ and the heating time is 6~48h.

[0010] In step (3), the sintering temperature is 300~800℃ and the sintering time is 0.5~10h.

[0011] In step (4), the ratio of ethylene glycol, ethanol, WCl6 and citric acid is (100mL): (50~200mL): (1~5g): (5~25g); the oil bath heating temperature is 80~200℃ and the heating time is 0.5~2h.

[0012] In step (4), the concentration of the added sodium hydroxide solution is 0.1~1M; the volume ratio of the added sodium hydroxide solution to ethylene glycol is (2~5):1; and the reaction time after adding the sodium hydroxide solution is 8~24h.

[0013] This invention forms dense, irregular TiO2 nanosheets on the surface of medical titanium alloy materials via hydrothermal oxidation, and then deposits WCl6 onto the TiO2 nanosheets by reducing WCl6 in an alcohol solution. 18 O 49 Quantum dots. TiO2 nanosheets and W 18 O 49 Quantum dots form heterojunctions, such as Figure 1 As shown, under near-infrared illumination, W 18 O 49 Absorbing near-infrared light forms electron-hole pairs, and the electrons migrate into the TiO2 nanosheets, forming a heterojunction. This heterojunction can suppress W... 18 O 49 The recombination of electrons and holes in the middle; simultaneously in W 18 O 49 Quantum dots form hole-rich sites, which can efficiently oxidize oxygen in the environment to produce ROS. ROS has antibacterial properties, thus providing antibacterial effects.

[0014] Compared with existing technologies, this invention has the following significant advantages: the medical titanium alloy material prepared by this invention has a highly efficient catalytic effect on the surface to generate ROS, thereby achieving efficient sterilization. On the one hand, TiO2 nanosheets and W... 18 O 49 Quantum dots form heterojunctions, suppressing electron-hole recombination and thus improving catalytic efficiency; on the other hand, small-sized W 18 O 49 Quantum dots possess "single-atom-like catalysis" characteristics, enabling the vast majority of W... 18 O 49 Both are located on high-energy surfaces, which improves W 18 O 49 The utilization efficiency is improved. Furthermore, the excitation light used to enhance the antibacterial properties of the medical titanium alloy material prepared in this invention is near-infrared light, which has better tissue penetration than visible light. Attached Figure Description

[0015] Figure 1 This is a schematic diagram illustrating the principle of the antibacterial functionalization treatment of the surface of the medical titanium alloy material of the present invention; Figure 2 Scanning electron microscope image of TiO2 nanosheets on the surface of the medical titanium alloy material prepared in this invention; Figure 3 The medical titanium alloy material prepared according to this invention has TiO2 nanosheets / W on its surface. 18 O 49 Transmission electron microscopy images and elemental analysis of quantum dot heterojunctions; Figure 4 The medical titanium alloy material prepared according to this invention has TiO2 nanosheets / W on its surface.18 O 49 Bright-field and dark-field images and elemental analysis of quantum dot heterojunctions under transmission electron microscopy; Figure 5 Unloaded W prepared for Comparative Example 1 of this invention 18 O 49 Bright-field and dark-field images and elemental analysis of quantum dot heterojunctions under transmission electron microscopy; Figure 6 These are absorption spectra of solutions after different treatments in the embodiments of the present invention; Figure 7 This is a statistical chart showing the ROS generation of the materials prepared in the embodiments and comparative examples of the present invention; Figure 8 The images show the antibacterial effects of different treatments on medical titanium alloy materials in the embodiments and comparative examples of this invention. Detailed Implementation

[0016] The present invention will be further described below with reference to the accompanying drawings and embodiments. Unless otherwise specified, the preparation methods and usage conditions used in the following embodiments are conventional methods; unless otherwise specified, the reagents and materials used in the following embodiments are commercially available. Example 1

[0017] 1) The titanium alloy material was sequentially immersed in acetone, ethanol, and deionized water, and simultaneously ultrasonically cleaned. 2) The cleaned surface area is approximately 2cm² 2 The titanium alloy material was immersed in 10 mL of a mixed solution containing 0.1 mol KMnO4 and 0.2 mol NaOH, placed in a hydrothermal reactor, heated at 180 °C for 12 h, rinsed with deionized water and dried. 3) The treated titanium alloy material was sintered in a box-type resistance furnace at 550°C for 2 hours; 4) Add 1g WCl6 and 5g citric acid to a mixture containing 100mL ethylene glycol and 100mL ethanol. After complete dissolution, immerse the titanium alloy material in the mixture. Heat in an oil bath at 160℃ under nitrogen atmosphere and reflux for 1 hour. After natural cooling, add 200mL of 0.2M sodium hydroxide solution and react for 12 hours. Rinse with deionized water and dry to obtain TiO2 nanosheets / W 18 O 49 A medical titanium alloy surface functionalized with quantum dot heterostructures. Example 2

[0018] 1) The titanium alloy material was sequentially immersed in acetone, ethanol, and deionized water, and simultaneously ultrasonically cleaned. 2) The cleaned surface area is approximately 2cm² 2The titanium alloy material was immersed in 10 mL of a mixed solution containing 0.1 mol KMnO4 and 1 mol NaOH, placed in a hydrothermal reactor, heated at 200 °C for 12 h, rinsed with deionized water and dried. 3) The treated titanium alloy material was sintered in a box-type resistance furnace at 450°C for 5 hours; 4) Add 1g WCl6 and 5g citric acid to a mixture containing 100mL ethylene glycol and 100mL ethanol. After complete dissolution, immerse the titanium alloy material in the mixture. Heat in an oil bath at 160℃ under nitrogen atmosphere and reflux for 1 hour. After natural cooling, add 200mL of 0.2M sodium hydroxide solution and react for 12 hours. Rinse with deionized water and dry to obtain TiO2 nanosheets / W 18 O 49 A medical titanium alloy surface functionalized with quantum dot heterostructures. Example 3

[0019] 1) The titanium alloy material was sequentially immersed in acetone, ethanol, and deionized water, and simultaneously ultrasonically cleaned. 2) The cleaned surface area is approximately 2cm² 2 The titanium alloy material was immersed in 10 mL of a mixed solution containing 0.1 mol KMnO4 and 0.2 mol NaOH, placed in a hydrothermal reactor, heated at 180 °C for 12 h, rinsed with deionized water and dried. 3) The treated titanium alloy material was sintered in a box-type resistance furnace at 550°C for 2 hours; 4) Add 2g WCl6 and 5g citric acid to a mixture containing 100mL ethylene glycol and 80mL ethanol. After complete dissolution, immerse the titanium alloy material in the mixture. Heat in an oil bath at 90℃ under nitrogen atmosphere and reflux for 1 hour. After natural cooling, add 200mL of 1M sodium hydroxide solution and react for 12 hours. Rinse with deionized water and dry to obtain TiO2 nanosheets / W 18 O 49 A medical titanium alloy surface functionalized with quantum dot heterostructures. Example 4

[0020] The medical titanium alloy material was treated using the same method as in Example 1, except that the 10 mL mixed solution contained 0.02 mol KMnO4 and 0.02 mol NaOH. Example 5

[0021] The medical titanium alloy material was treated using the same method as in Example 1, except that the 10 mL mixed solution contained 0.5 mol KMnO4 and 0.5 mol NaOH. Example 6

[0022] The medical titanium alloy material was treated using the same method as in Example 1, except that 10 mL of the mixed solution contained 1.0 mol KMnO4 and 1.0 mol NaOH. Example 7

[0023] The medical titanium alloy material was treated using the same method as in Example 1, except that in step 2), the material was heated at 150°C for 48 hours in a hydrothermal reactor. Example 8

[0024] The medical titanium alloy material was treated using the same method as in Example 1, except that in step 2), the material was heated at 220°C for 6 hours in a hydrothermal reactor. Example 9

[0025] The medical titanium alloy material was treated using the same method as in Example 1, except that in step 3), it was sintered at 300°C for 10 hours. Example 10

[0026] The medical titanium alloy material was treated using the same method as in Example 1, except that in step 3), it was sintered at 800°C for 0.5 hours. Example 11

[0027] The medical titanium alloy material was treated using the same method as in Example 1, except that 100 mL of ethylene glycol, 50 mL of ethanol, 61 g of WCl, and 15 g of citric acid were used. Example 12

[0028] The medical titanium alloy material was treated using the same method as in Example 1, except that 100 mL of ethylene glycol, 200 mL of ethanol, 65 g of WCl, and 25 g of citric acid were used. Example 13

[0029] The medical titanium alloy material was treated using the same method as in Example 1, except that: step 4) oil bath heating at 80°C and reflux for 2 hours. Example 14

[0030] The medical titanium alloy material was treated using the same method as in Example 1, except that: step 4) oil bath heating at 200°C and reflux for 0.5 h. Example 15

[0031] The medical titanium alloy material was treated using the same method as in Example 1, except that in step 4), 500 mL of 0.1 M sodium hydroxide solution was added and reacted for 24 h. Example 16

[0032] The medical titanium alloy material was treated using the same method as in Example 1, except that in step 4), 500 mL of 0.5 M sodium hydroxide solution was added and reacted for 8 hours.

[0033] Comparative Example 1 1) The titanium alloy material was sequentially immersed in acetone, ethanol, and deionized water, and simultaneously ultrasonically cleaned. 2) The cleaned surface area is approximately 2cm² 2 The titanium alloy material was immersed in 10 mL of a mixed solution containing 0.1 mol KMnO4 and 0.2 mol NaOH, placed in a hydrothermal reactor, heated at 180 °C for 12 h, rinsed with deionized water and dried. 3) The treated titanium alloy material was sintered in a box-type resistance furnace at 550°C for 2 hours to obtain unloaded W 18 O 49 Quantum dot TiO2 nanosheets.

[0034] Comparative Example 2 1) The titanium alloy material was sequentially immersed in acetone, ethanol, and deionized water, and simultaneously ultrasonically cleaned. 2) The cleaned surface area is approximately 2cm² 2 The titanium alloy material was immersed in a mixture containing 100 mL of ethylene glycol and 100 mL of ethanol, with 1 g of WCl6 and 5 g of citric acid added. After the mixture was fully dissolved, the titanium alloy material was immersed in the mixture. Under nitrogen atmosphere protection, the mixture was heated in an oil bath at 160°C and refluxed for 1 hour. After natural cooling, 200 mL of 0.2 M sodium hydroxide solution was added and the mixture was reacted for 12 hours. The mixture was then rinsed with deionized water and dried.

[0035] Performance testing: The surface of the sintered titanium alloy material prepared in step 3) of Example 1 was observed using a scanning electron microscope, and the results are as follows: Figure 2 As shown, the prepared medical titanium alloy material exhibits a dense, irregular sheet-like structure on its surface.

[0036] The medical titanium alloy materials treated in Example 1 and Comparative Example 1 were scraped off the surface, dissolved in anhydrous ethanol, and dropped onto a copper grid. The morphology was observed by transmission electron microscopy, and elemental analysis was performed. Figure 3 The sample prepared in Example 1 shows a large amount of Ti and O elements in the sheet-like structure, along with W, consistent with the TiO2 nanosheet / W ratio. 18 O 49 Structural characteristics of quantum dots. Further local magnification (e.g.) Figure 4 As shown), utilizing electrons in TiO2 nanosheets and W 18 O 49The difference in penetration within quantum dots allowed for the observation of numerous dot-like structures on the nanosheets using both bright-field and dark-field TEM. Statistical measurements using a scale bar indicated that the diameter of these dot-like structures was approximately 2–4 nm. Combined with elemental analysis, it can be deduced that the prepared structure is a TiO2 nanosheet / W 18 O 49 Quantum dot heterojunction structure. Figure 5 Unloaded W prepared for Comparative Example 1 18 O 49 Quantum dot TiO2 nanosheets, representing W 18 O 49 The high-contrast dot structure of quantum dots does not exist, and the element W is no longer present in elemental analysis.

[0037] Medical titanium alloy materials that were not treated according to this invention, as well as materials prepared in Examples 1-3, were respectively immersed in 0.1M 1,3-diphenylisobenzofuran (DPBF) solution and irradiated with near-infrared light for 10 min. The absorbance of the solutions in the 300-600 nm wavelength range was then examined. The results are as follows: Figure 6 As shown, DPBF has an absorption peak at 410 nm, which disappears after reacting with ROS. Therefore, a 0.1 mol / L DPBF solution was first prepared and divided into multiple portions. Different samples were then immersed in the DPBF solution, and the absorbance values ​​were compared with those of the "untreated DPBF solution" group. The degree of decrease in absorbance value reflects the ROS formation. Figure 6 It can be seen that the untreated medical titanium alloy produces almost no ROS under near-infrared light irradiation, while the materials prepared in Examples 1-3 produce a large amount of ROS after 10 minutes of near-infrared light irradiation.

[0038] Using the above method, the ROS generation of untreated titanium alloy material (sample 1), samples prepared in Examples 1-15, and samples in Comparative Examples 1-2 were statistically analyzed. The relative value was calculated with the ROS generation of sample 1 as 100%. The results are as follows: Figure 7 As shown, it can be observed that the samples prepared in Examples 1-15 can all generate large amounts of ROS, while Comparative Example 1 without W loading... 18 O 49 Quantum dots and Comparative Example 2 did not generate TiO2, thus significantly reducing the amount of ROS generated.

[0039] Staphylococcus aureus stock solution was divided into four groups: untreated (control group), immersed in untreated titanium alloy material and irradiated with near-infrared light for 10 min, immersed in titanium alloy material treated in Example 1 and irradiated with near-infrared light for 10 min, immersed in titanium alloy material treated in Example 2 and irradiated with near-infrared light for 10 min, immersed in titanium alloy material treated in Comparative Example 1 and irradiated with near-infrared light for 10 min, and immersed in titanium alloy material treated in Comparative Example 2 and irradiated with near-infrared light for 10 min. Then, 40 μL of each treatment solution was added to agar medium and cultured for 24 h. The colony formation was then observed, and the results are as follows: Figure 8 As shown. It can be seen that only the TiO2 nanosheets / W prepared according to Examples 1 and 2 of the present invention... 18 O 49 The surface of quantum dot-functionalized titanium alloy exhibits excellent antibacterial effects under near-infrared light irradiation, with an antibacterial efficiency ≥99%. This is attributed to the high ROS generation rate under near-infrared light irradiation. Untreated titanium alloy and Comparative Example 1 (without W loading) are also mentioned. 18 O 49 Quantum dots and the control group (without TiO2 formation) showed almost no antibacterial effect.

Claims

1. A method for surface antibacterial functionalization of medical titanium alloy materials, characterized in that: The surface of the medical titanium alloy is composed of TiO2 nanosheets / W 18 O 49 Quantum dot heterostructures are formed.

2. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 1, characterized in that: W 18 O 49 The size is as small as 2~4 nm and it is uniformly distributed on TiO2 nanosheets.

3. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 1, characterized in that: The surface of the medical titanium alloy material has photodynamic antibacterial properties.

4. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 1 or 2, characterized in that: Includes the following steps: (1) The titanium alloy material was immersed in acetone, ethanol and deionized water in sequence, and ultrasonic cleaning was performed simultaneously; (2) Immerse the cleaned titanium alloy material in a mixed solution of KMnO4 and NaOH, heat it in a hydrothermal reaction vessel, rinse it with deionized water and dry it. (3) The titanium alloy material after the above treatment is sintered at high temperature; (4) Add WCl6 and citric acid to the ethylene glycol / ethanol mixture. After it is fully dissolved, immerse the above titanium alloy material in it. Heat it in an oil bath under nitrogen atmosphere and reflux. After natural cooling, add sodium hydroxide solution to react. Rinse with deionized water and dry.

5. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 4, characterized in that: In step (2), the ratio of titanium alloy surface area, KMnO4, and NaOH is (1 mm²) 2 ): (0.1~5mmol): (0.1~5mmol).

6. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 4, characterized in that: In step (2), the temperature of the heat treatment is 150~220℃ and the heating time is 6~48h.

7. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 4, characterized in that: In step (3), the sintering temperature is 300~800℃ and the sintering time is 0.5~10h.

8. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 4, characterized in that: In step (4), the ratio of ethylene glycol, ethanol, WCl6 and citric acid is (100mL): (50~200mL): (1~5g): (5~25g); the oil bath heating temperature is 80~200℃ and the heating time is 0.5~2h.

9. The method for surface antibacterial functionalization of medical titanium alloy materials according to claim 4, characterized in that: In step (4), the concentration of the added sodium hydroxide solution is 0.1~1M; the volume ratio of the added sodium hydroxide solution to ethylene glycol is (2~5):1; and the reaction time after adding the sodium hydroxide solution is 8~24h.

10. Medical titanium alloy material obtained by the surface antibacterial functionalization treatment method of medical titanium alloy material according to any one of claims 1-9.

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