CN114949374A - Antibacterial bone-promoting dual-function titanium metal orthopedic implant and preparation method thereof - Google Patents
Antibacterial bone-promoting dual-function titanium metal orthopedic implant and preparation method thereof Download PDFInfo
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- CN114949374A CN114949374A CN202210570697.0A CN202210570697A CN114949374A CN 114949374 A CN114949374 A CN 114949374A CN 202210570697 A CN202210570697 A CN 202210570697A CN 114949374 A CN114949374 A CN 114949374A
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- titanium metal
- titanium
- antibacterial
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- aqueous solution
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Abstract
The invention discloses an antibacterial osteogenesis promoting bifunctional titanium metal orthopedic implant and a preparation method thereof. The titanium metal obtained by the invention has enhanced antibacterial property and osteogenesis activity, and can be widely used as clinical medical materials.
Description
Technical Field
The invention relates to the field of antibacterial orthopedic implants, in particular to an antibacterial osteogenesis-promoting bifunctional titanium orthopedic implant and a preparation method thereof.
Background
Open fracture is a common disease and frequently encountered disease in orthopedic trauma, and refers to that the skin and soft tissues at the fracture part are cracked due to direct or indirect violence factors, the fracture end is directly communicated with the outside, the open fracture caused by various frequent traffic accidents is increasingly serious and complex, and the treatment is increasingly difficult. Effective control of infection is critical in determining success in the treatment of open fractures. Due to the damage of the soft tissue of the skin, the bone is directly communicated with the outside and contacted with bacteria to be polluted. As bacteria proliferate within the wound, serious infections develop. Even if the patient can be timely and correctly treated by debridement, irrigation, fixation, closure, infection resistance and the like, infection still occurs at all times. Finally, the bone fracture can not be healed, the traumatic osteomyelitis can be caused, the healing time is prolonged, the operation frequency is increased, and even amputation or death can be caused in serious patients, so that huge mental and physical burden is brought to the patients. The infection rates for various types of open fractures are reported to be 0% to 2% for type I, 2% to 5% for type II, 5% to 10% for type IIIA, 10% to 50% for type IIIB, and 25% to 50% for type iiic, respectively. Therefore, how to control infection more effectively becomes a problem of great concern to clinicians. In recent years, with the development of more and more researches on adjuvant therapy of open fracture by using slow-release antibiotic systems, it has been generally considered that local slow-release antibiotic systems have important significance in the therapy of open fracture. On one hand, the local antibiotic slow release system can accurately generate higher drug concentration at the local focus, and simultaneously reduces the drug concentration in serum, thereby reducing the toxic and side effect of the drug. However, local antibiotic treatment has the problem that the excessive use of antibiotics causes multiple drug-resistant bacteria, and further causes greater risks.
Titanium (Ti) and its alloys are widely used as implantable materials for orthopedic, orthopedic and dental applications due to their excellent mechanical properties, corrosion resistance and biocompatibility. However, the original Ti surface is a good breeding ground for opportunistic pathogens. Furthermore, due to its biological inertness, pristine Ti is not able to induce or stimulate sufficiently specific cellular behaviour, eventually leading to poor integration with the surrounding bone tissue and hindering new bone formation. These drawbacks of the original Ti can lead to implant failure and even tissue necrosis, and in severe cases even require removal of the implant and repeated surgery, which can be painful and economically burdensome to the patient. Therefore, Ti-based implants with enhanced antibacterial activity and favoring osteoblast growth are highly desirable.
To date, methods for improving the bioactivity of Ti-based implants have been reported to be hydrothermal treatment, anodic oxidation, micro-arc oxidation, plasma immersion, and the like. Among them, the anodic oxidation method is widely used to etch a Ti substrate and form a titanium dioxide nanotube (TNT) on the surface thereof because of a simple preparation process and low cost. The tubular array structure of the TNT can enlarge the surface area of Ti and improve the surface roughness of the Ti. In addition, TNT with an appropriate diameter (about 70nm) is effective in improving the bioactivity of Ti substrates. In particular, TNT can promote differentiation of preosteoblasts by affecting adsorption of fibrinogen and fibronectin, regulating cell signaling pathways and affecting cellular responses through its nanoroughness. Furthermore, the tubular structure is often loaded with a biocide to impart anti-bacterial capabilities to the TNT. Heavy metal based fungicides such as silver are typically loaded into TNT and then the TNT is released to exert a biocidal effect. However, the scale-up of this approach is limited by the potential health risks of dose-dependence, cytotoxicity, etc. of heavy metal ions/nanoparticles. Similarly, loading antibiotics into TNT may also be effective in preventing the occurrence of BAI, but overuse of antibiotics may lead to the emergence of multidrug-resistant bacteria, thereby creating a greater risk. In recent years, a method of introducing molecules having antibacterial activity on the surface of a Ti substrate by covalent grafting to form a non-leachable coating on the surface thereof has been attracting attention due to its high stability and long-lasting antibacterial activity.
The fact that the variety of antibacterial molecules which can be introduced into the Ti substrate by a covalent grafting mode is more, how to select a proper antibacterial molecule and graft the proper antibacterial molecule onto the Ti substrate in a proper mode is the key for successfully implementing the strategy, and then the implant which has higher antibacterial activity, is beneficial to the growth of osteoblasts and has high stability is obtained.
Guanidine antibacterial agents have been reported as a new-generation disinfectant at home and abroad in recent years, and common guanidine antibacterial agents include polyhexamethylene monoguanidine, polyhexamethylene biguanide, and a polyguanidine derivative thereof. The special high molecular polymer structure of the disinfectant reduces the toxicity of the disinfectant, has more excellent bactericidal effect, is widely applied to various fields such as medical treatment and health, family life, food industry and the like, and the application of the disinfectant is continuously developed along with the research on the properties and the effects of guanidine disinfectants.
Currently, according to the research on mono-guanidine and biguanide at home and abroad, biguanide is generally considered to have higher safety and lower irritation than mono-guanidine in terms of safety, and is already listed in the raw material list allowed by the nation, so that biguanide has more advantages than polyhexamethylene monoguanidine in terms of production and application of orthopedic implant materials. Guanidine groups in PHMB have high activity, are positively charged in aqueous solution, can be adsorbed by negatively charged bacterial cell membranes, and exchange ions with calcium ions and magnesium ions in the bacterial cell membranes to destroy the charge balance of the cell membranes, finally destroy the membrane systems of the bacterial cells, cause the bacterial lysis by the outflow of substances in the bacterial bodies, and block the respiratory channels of microorganisms to inhibit the propagation of the bacteria. The guanidine polymer basically does not generate target-target specific combination with bacteria when realizing antibacterial action, so that the guanidine polymer is not easy to generate drug resistance. Meanwhile, the outer layer of the mammalian cell membrane is neutral, and the outer layer of the bacterial/fungal cell membrane is negatively charged, so that the guanidine polymer with positive charge has strong selectivity on the bacterial or fungal cell membrane, and the toxicity of the guanidine polymer on the mammalian cells is further reduced.
At present, the prior art discloses a method for preparing a calcium-phosphorus coating on the porous surface of a metal implant, which can improve the osseointegration performance of the metal implant. But the biomaterial surface which can promote the adhesion and the growth of bone cells is also suitable for the colonization of bacteria, in particular to a porous titanium metal orthopedic implant, although the porous titanium implant has the characteristics of strong osseointegration capability and individual adaptation to a complex-shaped part, the porous characteristic of the titanium implant greatly increases the integration surface area of the bone and the prosthesis, which can also increase the infection probability. Related infection of orthopedic implants is a common complication of orthopedic surgery, and often causes delayed bone healing, even bone nonunion and loosening of the implants, thereby causing prolonged use of antibiotics and even failure of the surgery. Therefore, the titanium metal is necessary to be further endowed with an antibacterial function on the basis of the titanium metal, so that the occurrence of related infection of plants in orthopedics can be effectively avoided, and the titanium metal is better applied to clinic.
Disclosure of Invention
Aiming at the problem that the metal implant in the prior art can increase the probability of bacterial infection while promoting osseointegration, the invention provides an antibacterial osteogenesis-promoting bifunctional titanium metal implant which has enhanced antibacterial property and osteogenesis activity and can be widely used as clinical medical materials.
In order to solve the technical problems, the invention adopts the following technical scheme:
a preparation method of an antibacterial bone-promoting bifunctional titanium metal orthopedic implant comprises the following steps:
(1) carrying out surface treatment on medical titanium metal by using an anodic oxidation method to form a titanium dioxide nanotube array film on the surface of the titanium metal;
(2) immersing the titanium metal treated in the step (1) into a phosphoric acid solution for room-temperature activation;
(3) cleaning and drying the activated titanium metal, and immersing the titanium metal into CoCl 2 ·6H 2 Performing room temperature treatment in an O aqueous solution, taking out and drying, and performing heat treatment in air at 300 ℃ for 1 hour to form a metal-phosphate double-layer film;
(4) and (3) at the constant temperature of 20-40 ℃, placing the titanium metal treated in the step (3) into a succinic anhydride aqueous solution for reaction for 0.5-1 h, then adding EDC and NHS for activating surface carboxyl for 0.5-1 h, then adding PHMB for reaction for 6-12 h, cleaning and drying the obtained sample, and obtaining the antibacterial bone-promoting dual-function titanium metal orthopedic implant.
Further, in the step (1), the electrolyte used in the anodic oxidation method is NH 4 F-ethylene glycol system, the voltage applied to the anode is 20-50V, and the anodic oxidation time is1-4h。
Further, in the step (1), the pipe diameter of the prepared titanium dioxide nanotube array is 60nm-90 nm.
Further, in the step (2), the mass concentration of the phosphoric acid solution is 0.5-5%, and the activation time is 1-4 h.
Further, in the step (3), the CoCl 2 ·6H 2 The concentration of the O aqueous solution is 0.1M-0.3M, and the room temperature treatment time is 1-3 h.
Further, in the step (4), the mass ratio of succinic anhydride, EDC, NHS and PHMB is 1: 1: 1: 0.1.
further, in the step (4), the concentration of the succinic anhydride aqueous solution is 0.01 g/mL.
The antibacterial osteogenesis promoting bifunctional titanium metal orthopedic implant obtained by the invention has enhanced antibacterial performance and osteogenesis activity, and can be widely used as clinical medical materials.
The invention has the beneficial effects that:
1. according to the invention, the metal-phosphate double-layer film and PHMB are grafted on the surface of the titanium metal implant with the anodic oxidation coating, multiple combination effects are generated among the substances, and the PHMB is firmly adsorbed and fixed on the surface of the metal implant, so that the metal implant provided by the invention has stronger antibacterial capability, the surface of the metal implant can be effectively killed after being contacted for 3min, and the same effect can be achieved after the traditional inner plants are contacted for a longer time.
2. The PHMB is grafted on the surface of the metal-phosphate double-layer film of the metal implant after the anodic oxidation treatment, so that the metal implant not only can promote osseointegration, but also can kill bacteria on the surface and around the implant, and the bacteria can be prevented from being adhered on the surface of the implant to form a biological film for a long time.
3. The raw material proportion and the reaction temperature screened by the method can optimize the performance of the titanium metal, particularly the sterilization performance.
Drawings
FIG. 1 is an SEM image of a TNT-Co-PHMB sample obtained in example 1 of the present invention, and it can be seen that the surface of the TNT nanotube array has a PHMB coating.
FIG. 2 is an SEM photograph of a TNT-Co-PHMB sample obtained in example 2 of the present invention;
FIG. 3 is an SEM photograph of a TNT-Co-PHMB sample obtained in example 3 of the present invention;
FIG. 4 is an SEM image of the original TNT nanotube array obtained in comparative example 2, wherein the diameter of the TNT tube is measured to be 70 nm.
FIG. 5 is a chart of WCA of samples obtained by the steps of example 2.
FIG. 6 is an EDS mapping chart of the TNT-Co-PHMB sample obtained in example 2, wherein the distribution of three elements of Co, N and P on the surface can be seen.
FIG. 7 is a photograph of plate-coating of the samples obtained in comparative examples 1 and 2 according to the present invention and the TNT-Co-PHMB and TNT-Co-PHMB samples obtained in example 2 for the bactericidal effect against Staphylococcus aureus at the same time.
Detailed Description
The following examples are given for the detailed implementation and specific operation of the present invention, but the scope of the present invention is not limited to the following examples.
Comparative example 1
High-purity titanium with the purity of 99.99 percent is adopted, and a titanium sheet is cut into square sheets with the thickness of 10mm multiplied by 1 mm. Sequentially polishing with 400#, 600#, 800#, 1000#, and 1200# water-based sand paper until the surface is smooth, sequentially ultrasonic cleaning with acetone, anhydrous ethanol, and pure water for 15min to remove surface oil stain, and then using HNO with volume ratio 3 :HF:H 2 And (3) ultrasonically polishing the chemical polishing solution with the ratio of O to O being 4:1:5 for 3min to obtain a titanium sheet with a smooth surface, finally, washing the titanium sheet with deionized water, and drying to obtain a pure Ti sheet serving as a reference.
Comparative example 2
High-purity titanium with the purity of 99.99 percent is adopted, and a titanium sheet is cut into square sheets with the thickness of 10mm multiplied by 1 mm. Sequentially polishing with 400#, 600#, 800#, 1000#, and 1200# water-based sand paper until the surface is smooth, sequentially ultrasonic cleaning with acetone, anhydrous ethanol, and pure water for 15min to remove surface oil stain, and then using HNO with volume ratio 3 :HF:H 2 Chemical polishing liquid ultrasound of O-4: 1:5Polishing for 3min to obtain smooth titanium sheet, washing with deionized water, and drying.
0.887g of NH 4 F. 97mL of ethylene glycol and 3mL of deionized water are mixed to prepare electrolyte, then a magnetic stirrer is used for slowly stirring at room temperature for 1h, and then a titanium sheet is soaked in the electrolyte to be used as an anode and a platinum electrode is used as a cathode. Subsequently, a voltage of 30V was applied at 30 ℃ for 60 minutes to perform an oxidation process. After annealing the sample at 450 ℃ for 1h, the sample was ultrasonically cleaned with deionized water and then dried to obtain a TNT sheet as a control.
Example 1
High-purity titanium with the purity of 99.99 percent is adopted, and a titanium sheet is cut into square sheets with the thickness of 10mm multiplied by 1 mm. Sequentially polishing with 400#, 600#, 800#, 1000#, and 1200# water-based sand paper until the surface is smooth, sequentially ultrasonic cleaning with acetone, anhydrous ethanol, and pure water for 15min to remove surface oil stain, and then using HNO with volume ratio 3 :HF:H 2 And ultrasonically polishing the chemical polishing solution with the ratio of O to O being 4:1:5 for 3min to obtain a titanium sheet with a smooth surface, finally washing the titanium sheet with deionized water, and drying the titanium sheet for later use.
0.887gNH 4 F. 97mL of ethylene glycol and 3mL of deionized water are mixed to prepare electrolyte, the mixture is slowly stirred for 1h at room temperature by a magnetic stirrer, and then a titanium sheet is soaked in the electrolyte to be used as an anode, and a platinum electrode is used as a cathode. Subsequently, a voltage of 30V was applied at 30 ℃ for 60 minutes to perform an oxidation process. Annealing the sample at 450 ℃ for 1h, ultrasonically cleaning the sample by using deionized water, and drying for later use.
The samples were soaked in a solution containing 5mL of 0.5% H at room temperature 3 PO 4 The solution was placed in a closed glass bottle for 60 minutes. The samples were then rinsed with deionized water and dried with nitrogen. The sample was then immersed in 5mL of 0.1M CoCl 2 ·6H 2 And O in water solution for 120 min. After removal from the solution, the sample was rinsed thoroughly with deionized water and dried with nitrogen. The sample was heat-treated in air at 300 ℃ for 1 hour to form a metal-phosphate bilayer film.
The sample is placed in 10mL of 0.01g/mL succinic anhydride aqueous solution at the constant temperature of 30 ℃ for reaction for 0.5h, then 0.1g of EDC and 0.1g of NHS are added for activating surface carboxyl for 0.5h, and finally 0.01g of PHMB is added for reaction for 6 h. And (3) washing the sample with pure water, and drying at 60 ℃ for 24h to obtain the TNT of the PHMB covalent grafted metal-phosphate double-layer membrane, which is recorded as TNT-Co-PHMB.
Example 2
High-purity titanium with the purity of 99.99 percent is adopted, and a titanium sheet is cut into square sheets with the thickness of 10mm multiplied by 1 mm. Sequentially polishing with 400#, 600#, 800#, 1000#, and 1200# water-based sand paper until the surface is smooth, sequentially ultrasonic cleaning with acetone, anhydrous ethanol, and pure water for 15min to remove surface oil stain, and then using HNO with volume ratio 3 :HF:H 2 And ultrasonically polishing the chemical polishing solution with the ratio of O to O being 4:1:5 for 3min to obtain a titanium sheet with a smooth surface, finally washing the titanium sheet with deionized water, and drying the titanium sheet for later use.
0.887gNH 4 F. 97mL of ethylene glycol and 3mL of deionized water are mixed to prepare electrolyte, the mixture is slowly stirred for 1h at room temperature by a magnetic stirrer, and then a titanium sheet is soaked in the electrolyte to be used as an anode, and a platinum electrode is used as a cathode. Subsequently, a voltage of 30V was applied at 30 ℃ for 60 minutes to perform an oxidation process. Annealing the sample at 450 ℃ for 1h, ultrasonically cleaning the sample by using deionized water, and drying for later use.
Samples were soaked in 5mL of 1% H at room temperature 3 PO 4 The solution was placed in a closed glass bottle for 60 minutes. The samples were then rinsed with deionized water and dried with nitrogen. The sample was then immersed in 5mL of 0.1M CoCl 2 ·6H 2 And O in water solution for 120 min. After removal from the solution, the sample was rinsed thoroughly with deionized water and dried with nitrogen. The sample was heat treated in air at 300 ℃ for 1 hour to form a metal-phosphate bilayer film (denoted as TNT-Co).
The sample is placed in 10mL of 0.01g/mL succinic anhydride aqueous solution at the constant temperature of 30 ℃ for reaction for 0.5h, then 0.1g of EDC and 0.1g of NHS are added for activating surface carboxyl for 0.5h, and finally 0.01g of PHMB is added for reaction for 6 h. And (3) washing the sample with pure water, and drying at 60 ℃ for 24h to obtain the TNT of the PHMB covalent grafted metal-phosphate double-layer membrane, which is recorded as TNT-Co-PHMB.
Example 3
High-purity titanium with the purity of 99.99 percent is adopted, and a titanium sheet is cut into square sheets with the thickness of 10mm multiplied by 1 mm. Sequentially polishing with 400#, 600#, 800#, 1000#, and 1200# water-based sand paper until the surface is smooth, sequentially ultrasonic cleaning with acetone, anhydrous ethanol, and pure water for 15min to remove surface oil stain, and then using HNO with volume ratio 3 :HF:H 2 And ultrasonically polishing the chemical polishing solution with the ratio of O to O being 4:1:5 for 3min to obtain a titanium sheet with a smooth surface, finally washing the titanium sheet with deionized water, and drying the titanium sheet for later use.
0.887gNH 4 F. 97mL of ethylene glycol and 3mL of deionized water are mixed to prepare electrolyte, the mixture is slowly stirred for 1h at room temperature by a magnetic stirrer, and then a titanium sheet is soaked in the electrolyte to be used as an anode, and a platinum electrode is used as a cathode. Subsequently, a voltage of 30V was applied at 30 ℃ for 60 minutes to perform an oxidation process. Annealing the sample at 450 ℃ for 1h, ultrasonically cleaning the sample by using deionized water, and drying for later use.
The samples were soaked in a solution containing 5mL of 2% H at room temperature 3 PO 4 The solution was placed in a closed glass bottle for 60 minutes. The samples were then rinsed with deionized water and dried with nitrogen. The sample was then immersed in 5mL of 0.1M CoCl 2 ·6H 2 And O in water solution for 120 min. After removal from the solution, the sample was rinsed thoroughly with deionized water and dried with nitrogen. The sample was heat-treated in air at 300 ℃ for 1 hour to form a metal-phosphate bilayer film.
The sample is placed in 10mL of 0.01g/mL succinic anhydride aqueous solution at the constant temperature of 30 ℃ for reaction for 0.5h, then 0.1g of EDC and 0.1g of NHS are added for activating surface carboxyl for 0.5h, and finally 0.01g of PHMB is added for reaction for 6 h. And (3) washing the sample with pure water, and drying at 60 ℃ for 24h to obtain the TNT of the PHMB covalent grafted metal-phosphate double-layer membrane, which is recorded as TNT-Co-PHMB.
SEM images of TNT-Co-PHMB samples obtained in examples 1, 2 and 3 are respectively shown in figures 1, 2 and 3, and SEM image of titanium metal surface titanium dioxide nanotube array obtained in comparative example 2 is shown in figure 4. As can be seen from the figure, the titanium dioxide nanotube morphology size of the products obtained in examples 1 and 2 is not greatly changed compared with that of comparative example 2, while example 3 has a large change in morphology due to the higher concentration of phosphoric acid used in the treatment.
FIG. 5 is a chart of WCA of samples from the steps of example 2, where it can be seen that the hydrophilicity of the surface of the anodized material is significantly increased, while the hydrophilicity is slightly decreased after grafting. Therefore, the titanium dioxide nanotube array morphology can greatly improve the hydrophilicity of the titanium metal, and is beneficial to improving the biocompatibility of the titanium metal. The appearance of the sample obtained in the example 2 is not changed greatly compared with the sample obtained in the comparative example 2, and the hydrophilicity is not greatly different from that of the sample obtained in the comparative example 2; the sample in example 3 has a tubular shape which is greatly changed due to the high concentration of phosphoric acid, which is not favorable for the biocompatibility of the material.
As shown in fig. 6, the TNT-Co-PHMB sample obtained in example 2 contains N, Co, and P elements, and is uniformly distributed, which indicates that the metal-phosphate bilayer film and PHMB are successfully grafted on the surface of titanium metal.
The samples obtained in the above examples were tested for bactericidal effect as follows:
a. preparation before experiment: preparing a plurality of 15mL glass test tubes, a plurality of 5mL glass test tubes, a plurality of 1.5mL centrifuge tubes, a lactose bile salt fermentation medium (LB), a lactose bile salt agar fermentation solid medium and a PBS buffer solution, performing high-pressure steam sterilization (121 ℃, 40min) for later use, cooling the lactose bile salt agar fermentation solid medium to 60 ℃, pouring a flat plate, and waiting for solidification to form a solid culture dish.
b. Shaking the bacteria: adding 10-12mL lactose bile salt fermentation medium (LB) into 15mL glass test tube, inoculating Escherichia coli or Staphylococcus aureus, placing in constant temperature oscillator, culturing at 37 deg.C and 160r/min for 18-20 hr to make colony count reach 5 × 10 8 CFU/mL。
c. And (4) sucking 3 mu L of the bacterial liquid obtained in the step b by using a pipette gun, adding the bacterial liquid into 4mL of deionized water, and uniformly shaking.
d. Taking 70 mu L of the bacterial suspension obtained in the step c into 70mLPBS buffer solution, and uniformly mixing to obtain mixed solution; samples prepared in each example were placed in clean petri dishes.
e. 30. mu.L of the bacterial dilution obtained in step c was added dropwise to the surface of the sample prepared in each example. And (3) after 3min, 5min and 7min respectively, putting the sample into a centrifuge tube, performing ultrasonic wave to collect bacterial liquid, coating a flat plate, putting a culture dish into a constant-temperature incubator for culture (the culture temperature is 30-37 ℃, and the culture time is 24-36h), and counting.
f. After the experiment is finished, the used sample of example 2 is recovered, deionized water is used for washing the surface of the sample, the experiment steps are repeated after the sample is naturally air-dried, and the number of colonies is recorded.
The results of the bactericidal performance test of the samples obtained in each example are shown in tables 1 and 2.
TABLE 1 Sterilization test for E.coli
| Sample (I) | 0min | 3min | 5min | 7min | Rate of sterilization |
| TNT-Co-PHMB of example 1 | 277 | 97 | 0 | 0 | 100％ |
| TNT-Co of example 2 | 322 | 298 | 283 | 275 | 14.6％ |
| TNT-Co-PHMB of example 2 | 254 | 76 | 0 | 0 | 100％ |
| Ti of comparative example 1 | 324 | 320 | 313 | 308 | 4.9％ |
| TNT of comparative example 2 | 289 | 277 | 255 | 254 | 11％ |
| Example 2 (secondary test after recovery) | 314 | 110 | 0 | 0 | 100％ |
| Example 2 (three tests after recovery) | 300 | 121 | 1 | 0 | 100％ |
TABLE 2 Sterilization test for Staphylococcus aureus
As can be seen by comparison, the TNT-Co-PHMB sample obtained in each example has significantly better performance than the TNT obtained in comparative example 2. The material can completely kill bacteria within 5 min. The TNT obtained in comparative example 2 and the TNT-Co obtained in example 2 have a certain bactericidal effect but have a poor effect compared with the TNT-Co-PHMB obtained in example 2, because the PHMB is absent and thus the fast and efficient bactericidal effect is not achieved. Meanwhile, the TNT-Co-PHMB has excellent stability, and the antibacterial performance of the TNT-Co-PHMB is not reduced after three experiments are repeated.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Any person skilled in the art may, using the teachings disclosed above, change or modify the equivalent embodiments with equivalent changes. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (8)
1. A preparation method of an antibacterial bone-promoting bifunctional titanium metal orthopedic implant is characterized by comprising the following steps:
(1) carrying out surface treatment on medical titanium metal by using an anodic oxidation method to form a titanium dioxide nanotube array film on the surface of the titanium metal;
(2) immersing the titanium metal treated in the step (1) into a phosphoric acid solution for room-temperature activation;
(3) cleaning and drying the activated titanium metal, and immersing the titanium metal into CoCl 2 ·6H 2 Carrying out room temperature treatment in an O aqueous solution, taking out and drying the O aqueous solution, and carrying out heat treatment for 1 hour in air at 300 ℃ to form a metal-phosphate double-layer film;
(4) and (3) at the constant temperature of 20-40 ℃, placing the titanium metal treated in the step (3) into a succinic anhydride aqueous solution for reaction for 0.5-1 h, then adding EDC and NHS for activating surface carboxyl for 0.5-1 h, then adding PHMB for reaction for 6-12 h, cleaning and drying the obtained sample, and obtaining the antibacterial bone-promoting dual-function titanium metal orthopedic implant.
2. The method of claim 1, wherein: in the step (1), the electrolyte used in the anodic oxidation method is NH 4 The voltage applied to the anode is 20-50V, and the anodic oxidation time is 1-4 h.
3. The production method according to claim 1 or 2, characterized in that: in the step (1), the prepared titanium dioxide nanotube array has a tube diameter of 60nm-90 nm.
4. The method of claim 1, wherein: in the step (2), the mass concentration of the phosphoric acid solution is 0.5-5%, and the activation time is 1-4 h.
5. The method of claim 1, wherein: in the step (3), the CoCl 2 ·6H 2 The concentration of the O aqueous solution is 0.1M-0.3M, and the room temperature treatment time is 1-3 h.
6. The method of claim 1, wherein: in the step (4), the mass ratio of succinic anhydride, EDC, NHS and PHMB is 1: 1: 1: 0.1.
7. the method of claim 1, wherein: in the step (4), the concentration of the succinic anhydride aqueous solution is 0.01 g/mL.
8. An antibacterial osteogenesis promoting bifunctional titanium metal orthopedic implant obtained by the preparation method of any one of claims 1 to 7.
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