Titanium implant, its preparation method and application

Abstract

The application discloses a titanium implant and a preparation method and application thereof, relates to the technical field of medical titanium materials, and discloses the titanium implant which comprises a titanium base, a hierarchical titanium dioxide nanotube array layer and a piezoelectric fiber layer. The titanium implant provided by the application can destroy bacterial cell membranes through positive charge traps formed on the hierarchical titanium dioxide nanotube array layer, realizes antibacterial function, and can realize anti-inflammatory function through the following steps: macrophages can be adhered to the piezoelectric fiber layer, and the piezoelectric self-stimulating electric field generated by the piezoelectric fiber layer can repolarize from pro-inflammatory M1 type macrophages to anti-inflammatory M2 type macrophages, and the titanium implant has a protective effect of reducing osteogenic damage in an inflammatory environment, and creates a good bone immune microenvironment.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical titanium materials, in particular to a titanium implant and a preparation method and application thereof. BACKGROUND

[0002] In recent years, the research and application of various biomedical materials have developed rapidly, and titanium and titanium alloy have become widely used in the professional fields of dental and orthopedic implant materials due to their excellent biocompatibility and corrosion resistance. However, pure titanium implants have biological inertia, and the bone bonding ability is still insufficient. Surface modification of titanium implants, optimization of the surface properties of titanium implants, and influence on the biological effects around the titanium implants ultimately improve the bone bonding ability of the interface, which has been one of the research hotspots of biomedical materials in recent years.

[0003] The skilled person knows that planktonic bacteria are easily attached to the surface of the implant and rapidly proliferate, which greatly affects the integration of the implant and its surrounding tissue, and a large dose of antibiotics must be injected to overcome this problem in clinical practice. However, with the development of bacterial drug resistance, the method of injecting a large dose of antibiotics to avoid infection and inflammation during implantation has become less effective, which directly leads to an increased risk of implant failure. Worse still, due to long-term infection and inevitable rejection, the implant site produces unsatisfactory bone integration, causing irreversible damage, which significantly increases the clinical risk and economic loss. Therefore, it is crucial to develop multifunctional titanium implants with antibacterial, anti-inflammatory and osteogenic effects. SUMMARY

[0004] The technical problem to be solved by the present application is to provide a titanium implant and a preparation method thereof, which has multifunctional effects of antibacterial, anti-inflammatory and osteogenic, and has good application prospects.

[0005] The technical problem to be solved by the present application is solved by the following technical solution:

[0006] One of the objects of the present application is to provide a titanium implant comprising a titanium substrate, a hierarchical titanium dioxide nanotube array layer and a piezoelectric fiber layer.

[0007] The second object of the present application is to provide a preparation method of the aforementioned titanium implant, comprising the following steps:

[0008] (1) Anodizing the titanium substrate M0 in the presence of an electrolyte to obtain a titanium substrate M3 with a deposited hierarchical titanium dioxide nanotube array layer;

[0009] (2) Dispersing the piezoelectric material in an organic solvent to obtain a piezoelectric suspension, and then electrospinning the piezoelectric suspension on the surface of the titanium substrate M3 to obtain the titanium implant.

[0010] The third object of the present application is to provide a titanium implant obtained by the aforementioned preparation method.

[0011] The fourth object of the present application is to provide the aforementioned titanium implant for use in medical implant materials.

[0012] Compared with the prior art, the present application has the following beneficial effects:

[0013] 1. The titanium implant provided by the present application forms a large number of positive charge traps in the hierarchical titanium dioxide nanotube array layer during electrospinning, and the piezoelectric fiber layer has a proper pore size and negative potential, so as to ensure that bacteria can pass through to the hierarchical titanium dioxide nanotube array layer, and then the bacterial cell membranes are destroyed by the positive charge traps formed on the hierarchical titanium dioxide nanotube array layer, thereby realizing the antibacterial function.

[0014] 2. The titanium implant provided by the present application can adhere macrophages to the piezoelectric fiber layer, and repolarize the macrophages from pro-inflammatory M1 type to anti-inflammatory M2 type through the generated piezoelectric self-stimulating electric field, thereby realizing the anti-inflammatory function.

[0015] 3. The titanium implant provided by the present application has a protective effect of reducing osteogenic damage in an inflammatory environment, and creates a good bone immune microenvironment. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 Structure diagram of 3DMA prepared for Example 1;

[0017] Figure 2 、 3 Plate count and quantitative analysis results of Staphylococcus aureus and Escherichia coli grown on the surfaces of PT and 3DMA;

[0018] Figure 4 、 5 Macrophage immunofluorescence staining combined images and quantitative analysis results of PT and 3DMA groups, respectively taking CD206 and iNOS as markers of M2 and M1 phenotypes;

[0019] Figure 6 、 7 Micro CT images and Van Gieson staining images of hard tissue sections after implanting PT and 3DMA into the femurs of rats for four weeks, respectively;

[0020] Figure 8 、 9 Van Gieson staining images of hard tissue sections and quantitative analysis results after implanting PT and 3DMA into the femurs of rats for four weeks, respectively. DETAILED DESCRIPTION

[0021] In order to make the technical means, creative features, purposes and effects of the present application easy to understand, the present application is further described below in combination with specific examples and drawings.

[0022] The present application provides a titanium implant, comprising a titanium substrate, a hierarchical titanium dioxide nanotube array layer and a piezoelectric fiber layer.

[0023] The piezoelectric fiber layer is composed of piezoelectric fibers selected from at least one of polymer piezoelectric fibers, ceramic piezoelectric fibers and semiconductor piezoelectric fibers, preferably polymer piezoelectric fibers.

[0024] Further preferably, the polymer piezoelectric fibers are selected from at least one of PVDF fibers, PVDF-TrFE fibers, PHB fibers, PLLA fibers, PCL fibers, PLGA fibers, PHBV fibers, collagen fibers, chitosan fibers, cellulose and derivative fibers, PVP fibers, PVA fibers and PEO fibers.

[0025] Further preferably, the ceramic piezoelectric fibers are selected from at least one of barium titanate fibers, potassium sodium niobate fibers, lithium potassium sodium niobate fibers, lithium niobate fibers, strontium barium niobate fibers, lead zirconate titanate fibers, boron nitride fibers and hydroxyapatite fibers.

[0026] Further preferably, the semiconductor piezoelectric fibers are selected from at least one of CdS fibers, CdSe fibers, ZnO fibers, ZnS fibers, CdTe fibers, ZnTe fibers, GaAs fibers, GaSb fibers, InAs fibers, InSb fibers and AlN fibers.

[0027] The titanium implant provided by the present application forms a three-dimensional multifunctional structure composed of a hierarchical titanium dioxide nanotube array layer and a piezoelectric fiber layer on the surface of the titanium substrate, and further endows the surface of the titanium substrate with charge traps and piezoelectric self-stimulation. Due to suitable pore size and electrostatic interaction, bacteria can be eradicated through the piezoelectric fiber layer and the positive charge traps formed on the hierarchical titanium dioxide nanotube array layer; in addition, macrophages will adhere to the piezoelectric fiber layer, and be repolarized from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages through the generated piezoelectric self-stimulation electric field; and through further co-culture experiments, it is shown that the titanium implant provided by the present application with the three-dimensional multifunctional structure has a protective effect of reducing osteogenic damage in an inflammatory environment, and creates a good bone immune microenvironment.

[0028] Those skilled in the art know that macrophages play an important role in immune regulation. Regulating macrophage polarization (i.e., downregulating the pro-inflammatory phenotype M1 polarization and / or upregulating the anti-inflammatory phenotype M2 polarization) can suppress the secretion of pro-inflammatory cytokines by secreting a series of anti-inflammatory cytokines and other mediators, effectively promoting the subsidence of inflammation. At the same time, macrophages are electrically excitable cells that exhibit transient hyperpolarization characteristics. Electric fields can regulate macrophage polarization and promote the secretion of certain anti-inflammatory cytokines. Therefore, the concept of the present invention is to form an electrical stimulation to regulate the anti-inflammatory polarization phenotype of macrophages to achieve the anti-inflammatory effect of titanium implants, and further produce osteoblast-related proteins from M2 macrophages to promote osteogenesis and bone integration at the implant site.

[0029] The present invention also provides a method for preparing the aforementioned titanium implant, comprising the following steps:

[0030] (1) Anodizing the titanium substrate M0 in the presence of an electrolyte to obtain a titanium substrate M3 on which a graded titanium dioxide nanotube array layer is deposited;

[0031] (2) The piezoelectric material is dispersed in an organic solvent to obtain a piezoelectric suspension, and then the piezoelectric suspension is electrospun on the surface of the titanium substrate M3 to obtain a titanium implant.

[0032] The electrolyte is an ethylene glycol solution of ammonium fluoride, and the concentration of ammonium fluoride is 75-100 mmol / L, more preferably 88 mmol / L.

[0033] The anodization includes primary anodization and secondary anodization, that is, the hierarchical titanium dioxide nanotube array is formed through two anodization reactions under different conditions.

[0034] The conditions for the primary anodic oxidation are as follows: using graphite as the cathode, connecting the titanium substrate M0 to the anode, and performing the primary anodic oxidation to obtain the titanium substrate M1 loaded with the titanium dioxide nanotube array layer.

[0035] Preferably, the voltage of the initial anodization is 55-65 V, the temperature is 20-35° C., and the time is 2-3 h.

[0036] The conditions for the secondary anodization are as follows: the titanium dioxide nanotubes loaded on the surface of the titanium substrate M1 are cut off to obtain a titanium substrate M2 loaded with a bowl-shaped titanium dioxide nanoarray layer; then, graphite is used as the cathode, the titanium substrate M2 is connected to the anode, and secondary anodization is performed to obtain a titanium substrate M3 loaded with a graded titanium dioxide nanotube array layer.

[0037] Preferably, the truncation treatment is to place the titanium matrix M1 in an aqueous solution and perform ultrasonic treatment, with an ultrasonic power of 200-300 W and an ultrasonic time of 10-15 min.

[0038] Preferably, the voltage of the secondary anodic oxidation is 10-15V, the temperature is 20-35℃, and the time is 30-50min.

[0039] The piezoelectric material is selected from at least one of polymer piezoelectric material, ceramic piezoelectric material, and semiconductor piezoelectric material, and is preferably polymer piezoelectric material.

[0040] Further preferably, the polymer piezoelectric material is selected from at least one of PVDF, PVDF-TrFE, PHB, PLLA, PCL, PLGA, PHBV, collagen fiber, chitosan, cellulose and derivatives, PVP, PVA, and PEO.

[0041] Further preferably, the ceramic piezoelectric material is selected from at least one of barium titanate, potassium sodium niobate, lithium potassium sodium niobate, lithium niobate, strontium barium niobate, lead zirconate titanate, boron nitride, and hydroxyapatite.

[0042] Further preferably, the semiconductor piezoelectric material is selected from at least one of CdS, CdSe, ZnO, ZnS, CdTe, ZnTe, GaAs, GaSb, InAs, InSb, and AlN.

[0043] The mass concentration of the piezoelectric material in the piezoelectric suspension is 5-15wt%.

[0044] The organic solvent is selected from at least one of dimethyl sulfoxide, dimethyl formamide, dimethyl acetamide, dichloromethane, acetonitrile, tetrahydrofuran, acetone, N-methyl pyrrolidone, butyrolactone, phenol, m-cresol, caprolactam, sulfolane, and nitrobenzene; preferably, it is a mixture of DMF and acetone, and the mass ratio of DMF to acetone is (1-2):1.

[0045] The humidity of the electrospinning is 20-30%, the temperature is 20-30℃, the jet flow rate of the piezoelectric suspension is 0.5-2mL / h, the spinning distance is 10-15cm, the voltage applied to the piezoelectric suspension is 10-15KV, and the voltage applied to the titanium substrate M3 is -10--3KV.

[0046] In the present application, in order to prevent the oil stain or dirt on the surface of the titanium substrate from affecting the formation of the hierarchical titanium dioxide nanotube array layer, preferably, the titanium substrate is subjected to surface pretreatment, specifically, the surface of the titanium substrate is polished step by step by using metallographic sandpaper with different fineness, and then cleaned with an organic solvent and / or deionized water; the cleaning effect can be improved by ultrasonic treatment; preferably, the surface of the titanium sheet is polished step by step by using metallographic sandpaper with fineness from 800# to 7000#, and then subjected to ultrasonic treatment with acetone, ethanol, and deionized water, respectively.

[0047] In the preparation method of the titanium implant provided by the application, a titanium dioxide nanotube array is formed on the surface of a titanium substrate by an anodic oxidation reaction, and different levels of titanium dioxide nanotube array layers, i.e., a hierarchical titanium dioxide nanotube array layer, are formed on the surface of the titanium substrate by changing the conditions of the anodic oxidation reaction; and a material having a piezoelectric effect is formed on the surface of the hierarchical titanium dioxide nanotube array layer in the form of electrospinning to form a three-dimensional multifunctional structure. Specifically, the piezoelectric suspension forms a piezoelectric fiber layer after electrospinning, which has a proper pore size and a negative potential to ensure that bacteria can pass through the piezoelectric fiber layer and reach the hierarchical titanium dioxide nanotube array layer. Since a large amount of positive charges are injected into the hierarchical titanium dioxide nanotube array layer during the electrospinning process, a large number of positive charge traps are formed, so that bacteria can be killed.

[0048] The application further provides a titanium implant obtained by the preparation method.

[0049] The application further provides application of the aforementioned titanium implant in medical implant materials.

[0050] The application will be described in detail below through examples.

[0051] Example 1

[0052] (1) The surface of a pure titanium foil (PT, diameter 12 mm, thickness 0.25 mm, purity 99.99%) was polished step by step using 800# to 7000# metallographic sandpaper, and then ultrasonic treatment was performed using acetone, ethanol and deionized water, respectively. For the convenience of description, the pure titanium foil PT is defined as a titanium substrate M0.

[0053] (2) Primary anodic oxidation

[0054] The titanium substrate M0 was subjected to primary anodic oxidation, an ethylene glycol solution of ammonium fluoride with a concentration of 88 mmol / L was used as an electrolyte, graphite was used as a cathode, the titanium substrate M0 was connected to an anode, the voltage was controlled to be 60 V, and the primary anodic oxidation reaction was performed at 25℃ for 2.5 h to obtain a titanium substrate M1.

[0055] (3) Secondary anodic oxidation

[0056] The titanium substrate M1 was subjected to ultrasonic treatment in deionized water, the ultrasonic power was 200 W, and the ultrasonic time was 15 min to obtain a titanium substrate M2; then an ethylene glycol solution of ammonium fluoride with a concentration of 88 mmol / L was used as an electrolyte, graphite was used as a cathode, the titanium substrate M2 was connected to an anode, the voltage was controlled to be 12 V, and the secondary anodic oxidation reaction was performed at 25℃ for 40 min to obtain a titanium substrate M3.

[0057] (4) PVDF powder (FR904, Mw = 6 × 10 5 ) was dissolved in a mixed solution of DMF and acetone (the mass ratio of DMF to acetone was 1.5:1) to obtain a PVDF solution, wherein the concentration of the PVDF powder was 10 wt %; then, the PVDF solution was used as a raw material to form a piezoelectric fiber layer on the surface of the titanium substrate M3 by electrospinning, thereby obtaining a titanium implant.

[0058] Specific conditions for electrospinning: The piezoelectric fiber layer was prepared on the titanium substrate M3 using an electrospinning device (E05-001, Foshan Lepton Precision Electromechanical Technology Co., Ltd., China). The PVDF solution was subjected to a DC voltage of 12 kV, and the titanium substrate M3 was connected to the negative electrode at a voltage of -6 kV. The PVDF solution was delivered from the tip of a stainless steel needle at a flow rate of 1 mL / h, and the distance between the needle tip and the titanium substrate M3 was 12 cm. The relative humidity during electrospinning was 25%, and the temperature was 25°C.

[0059] Example 2

[0060] (1) The surface of a pure titanium foil (PT, 12 mm in diameter, 0.25 mm in thickness, 99.99% purity) was gradually polished using 800# to 7000# metallographic sandpaper. The surface was then ultrasonically treated with acetone, ethanol, and deionized water, respectively. For ease of description, the pure titanium foil PT is defined as the titanium matrix M0.

[0061] (2) Initial anodizing

[0062] The titanium substrate M0 was initially anodized using an ethylene glycol solution of ammonium fluoride with a concentration of 88 mmol / L as the electrolyte and graphite as the cathode. The titanium substrate M0 was connected to the anode with a controlled voltage of 65 V. The initial anodization reaction was carried out at 35°C for 2 h to obtain the titanium substrate M1.

[0063] (3) Secondary anodization

[0064] The titanium matrix M1 was placed in deionized water for ultrasonic treatment with an ultrasonic power of 300 W and an ultrasonic time of 15 min to obtain the titanium matrix M2; then, an ethylene glycol solution of ammonium fluoride with a concentration of 88 mmol / L was used as the electrolyte, graphite was used as the cathode, the titanium matrix M2 was connected to the anode, the voltage was controlled at 15 V, and a secondary anodic oxidation reaction was carried out at 35°C for 30 min to obtain the titanium matrix M3.

[0065] (4) PVP powder (K30, Mw = 3.79 × 10 4) was dissolved in a mixed solution of DMF and acetone (the mass ratio of DMF to acetone was 1:1) to obtain a PVP solution, wherein the concentration of the PVP powder was 10 wt %; then, the PVP solution was used as a raw material, and an electrospinning method was adopted to form a piezoelectric fiber layer on the surface of the titanium matrix M3 to obtain a titanium implant.

[0066] Specific conditions for electrospinning: The piezoelectric fiber layer was prepared on the titanium substrate M3 using an electrospinning device (E05-001, Foshan Lepton Precision Electromechanical Technology Co., Ltd., China). The PVP solution was subjected to a DC voltage of 10 kV, and the titanium substrate M3 was connected to the negative electrode with a voltage of -5 kV. The PVP solution was delivered from the stainless steel needle tip at a flow rate of 1 mL / h, and the distance between the needle tip and the titanium substrate M3 was 15 cm. The relative humidity during electrospinning was 30% and the temperature was 25°C.

[0067] Example 3

[0068] (1) The surface of a pure titanium foil (PT, 12 mm in diameter, 0.25 mm in thickness, 99.99% purity) was gradually polished using 800# to 7000# metallographic sandpaper. The surface was then ultrasonically treated with acetone, ethanol, and deionized water, respectively. For ease of description, the pure titanium foil PT is defined as the titanium matrix M0.

[0069] (2) Initial anodizing

[0070] The titanium substrate M0 was initially anodized using an ethylene glycol solution of ammonium fluoride with a concentration of 88 mmol / L as the electrolyte and graphite as the cathode. The titanium substrate M0 was connected to the anode with a controlled voltage of 55 V. The initial anodization reaction was carried out at 30°C for 3 hours to obtain a titanium substrate M1.

[0071] (3) Secondary anodization

[0072] The titanium matrix M1 was placed in deionized water for ultrasonic treatment with an ultrasonic power of 300 W and an ultrasonic time of 15 min to obtain the titanium matrix M2; then, an ethylene glycol solution of ammonium fluoride with a concentration of 88 mmol / L was used as the electrolyte, graphite was used as the cathode, the titanium matrix M2 was connected to the anode, the voltage was controlled at 10 V, and a secondary anodic oxidation reaction was carried out at 30°C for 50 min to obtain the titanium matrix M3.

[0073] (4) PCL powder (2200, Mw = 8 × 10 5 ) was dissolved in a mixed solution of DMF and acetone (the mass ratio of DMF to acetone was 2:1) to obtain a PCL solution, wherein the concentration of PCL powder was 10 wt %; then, the PCL solution was used as a raw material, and an electrospinning method was adopted to form a piezoelectric fiber layer on the surface of the titanium matrix M3 to obtain a titanium implant.

[0074] Specific electrospinning conditions: The piezoelectric fiber layer was prepared on the titanium substrate M3 using an electrospinning device (E05-001, Foshan Lepton Precision Electromechanical Technology Co., Ltd., China). The PCL solution was subjected to a DC voltage of 15 kV, and the titanium substrate M3 was connected to the negative electrode with a voltage of -8 kV. The PCL solution was delivered from the stainless steel needle tip at a flow rate of 1 mL / h, and the distance between the needle tip and the titanium substrate M3 was 10 cm. The relative humidity during electrospinning was 25%, and the temperature was 25°C.

[0075] Structural characterization and performance testing of titanium implants:

[0076] In order to facilitate the subsequent description and identification in the drawings of the specification, in the present invention, pure titanium foil is represented by PT, and the prepared three-dimensional multifunctional titanium implant is represented by 3DMA.

[0077] 1. Antibacterial performance evaluation of the titanium implant prepared in Example 1 was performed using Staphylococcus aureus and Escherichia coli:

[0078] A single colony was removed from Mueller-Hinton (MH) agar solid medium using a sterile loop and inoculated into 10 mL of MH broth. The culture was shaken on a shaker for 12 hours. Optical density (OD) was measured using a nucleic acid and protein analyzer to confirm thorough mixing of the bacterial broth and liquid medium. The bacterial suspension was then dropped onto the surface of polytetrafluoroethylene (PT) or 3DMA and incubated at 37°C for 2 hours. The sample was then washed with sterile phosphatase buffer (PBS) to remove loosely attached bacteria and placed into a centrifuge tube containing 5 mL of PBS. The sample was shaken on a vortex mixer for 5 minutes to allow the bacteria to fall from the PT or 3DMA surface into the PBS. A 20 μL aliquot of the PBS suspension containing bacteria from the centrifuge tube was then spread onto MH agar plates. The bacterial suspension was quickly and evenly spread across the plate. Repeat this process for three plates per centrifuge tube. The plates were incubated at 37°C for 12 hours, then removed and the number of CFU (colony forming units) of bacteria on each MH agar plate was counted.

[0079] The antibacterial rate was calculated as follows: [(XY) / X]×100%, where X represents the average bacterial colony count on the plates of the control group PT group, and Y represents the average bacterial colony count on the plates of the experimental group 3DMA group.

[0080] from Figure 2 It can be seen that the bacterial colonies of Staphylococcus aureus and Escherichia coli detected on the PT surface are more than those on the 3DMA surface prepared in Example 1. Compared with PT, the normalized CFU colony counts of Staphylococcus aureus and Escherichia coli on the 3DMA surface are 0.429 and 0.667 respectively. Figure 3 ). Therefore, the antibacterial rates of 3DMA against Staphylococcus aureus and Escherichia coli on the PT surface were 57.1% and 33.3%, respectively.

[0081] Based on the above experimental data, combined with the positive charge traps of the NT layer and the size effect of the nanofiber layer, the antibacterial activity of 3DMA is enhanced.

[0082] 2. Polarization phenotype evaluation of macrophage RAW264.7 on titanium implants prepared in Example 1:

[0083] RAW264.7 macrophages were seeded on PT or 3DMA, stimulated with LPS+IFN-γ for 24h, then fixed with 4% paraformaldehyde, broken with 0.25% Triton, blocked with 10% goat serum, and incubated with primary antibodies (Abcam; 1:100) of iNOS and CD206 and corresponding secondary antibodies. Positive cells of iNOS and CD206 were defined as M1 and M2 macrophages, respectively.

[0084] Figure 4 The results of immunofluorescence analysis of Example 1 show that under the stimulation of LPS and IFN-γ, the expression of M1 macrophage inflammatory marker iNOS is inhibited, and the expression of M2 macrophage surface marker CD206 is slightly increased. Figure 5 The results of quantitative analysis of Example 1 also show that compared with PT, 3DMA treatment can significantly inhibit the proportion of M1 macrophages, while increasing the proportion of M2 macrophages. This shows that 3DMA has a more ideal immune regulation effect of inhibiting M1 and promoting M2 polarization.

[0085] 3. Bone bonding performance evaluation of titanium implants prepared in Example 1 in rat in vivo implantation experiment:

[0086] 10-week-old male SD rats were used, and PT or 3DMA was implanted into the distal lateral femur of the rats. After 4 weeks, the samples were taken for Micro CT detection.

[0087] Figure 6 The micro-CT three-dimensional reconstruction images of Example 1 show that more new bone is formed in the 3DMA group. Figure 7 The two indicators reflecting new bone formation, bone volume percentage (BV / TV) and bone mineral density (BMD), were significantly higher in the 3DMA group than in the PT group. Figure 8 Figure 9 Van Gieson staining results of Example 1 show that the bone-implant contact rate of the 3DMA group is about 1.5 times that of the PT group. This shows that 3DMA improves bone bonding.

[0088] ​The above shows and describes the basic principles and main features of the present application and the advantages of the present application. Those skilled in the art should understand that the present application is not limited to the above embodiments, and the above embodiments and descriptions in the specification are only to illustrate the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the claimed present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. A titanium implant, characterized in that: The invention comprises a titanium substrate, a hierarchical titanium dioxide nanotube array layer and a piezoelectric fiber layer; The preparation method of the titanium implant comprises the following steps: (1) Anodizing the titanium substrate M0 in the presence of an electrolyte to obtain a titanium substrate M3 on which a graded titanium dioxide nanotube array layer is deposited; (2) The piezoelectric material is dispersed in an organic solvent to obtain a piezoelectric suspension, and then the piezoelectric suspension is electrospun on the surface of the titanium substrate M3 to obtain a titanium implant.

2. The titanium implant according to claim 1, wherein: The piezoelectric fiber layer is composed of piezoelectric fibers, and the piezoelectric fibers are selected from at least one of polymer piezoelectric fibers, ceramic piezoelectric fibers, and semiconductor piezoelectric fibers.

3. The titanium implant according to claim 2, wherein: The polymer piezoelectric fiber is selected from at least one of PVDF fiber, PVDF-TrFE fiber, PHB fiber, PLLA fiber, PCL fiber, PLGA fiber, PHBV fiber, collagen fiber, chitosan fiber, cellulose and derivative fiber, PVP fiber, PVA fiber, and PEO fiber.

4. The titanium implant according to claim 2, wherein: The ceramic piezoelectric fiber is selected from at least one of barium titanate fiber, potassium sodium niobate fiber, lithium potassium sodium niobate fiber, lithium niobate fiber, strontium barium niobate fiber, lead zirconate titanate fiber, boron nitride fiber, and hydroxyapatite fiber.

5. The titanium implant according to claim 2, wherein: The semiconductor piezoelectric fiber is selected from at least one of CdS fiber, CdSe fiber, ZnO fiber, ZnS fiber, CdTe fiber, ZnTe fiber, GaAs fiber, GaSb fiber, InAs fiber, InSb fiber, and AlN fiber.

6. The titanium implant according to claim 1, wherein: The electrolyte is an ethylene glycol solution of ammonium fluoride, and the concentration of ammonium fluoride is 75-100 mmol / L.

7. The titanium implant according to claim 1, wherein: The anodizing process includes primary anodizing and secondary anodizing.

8. The titanium implant according to claim 7, wherein: The conditions for the primary anodic oxidation are as follows: using graphite as the cathode, connecting the titanium substrate M0 to the anode, and performing the primary anodic oxidation to obtain the titanium substrate M1 loaded with the titanium dioxide nanotube array layer.

9. The titanium implant according to claim 8, wherein: The voltage of the initial anodization is 55-65V, the temperature is 20-35°C, and the time is 2-3h.

10. The titanium implant according to claim 7, wherein: The conditions for the secondary anodization are as follows: the titanium dioxide nanotubes loaded on the surface of the titanium substrate M1 are cut off to obtain a titanium substrate M2 loaded with a bowl-shaped titanium dioxide nanoarray layer; then, graphite is used as the cathode, the titanium substrate M2 is connected to the anode, and secondary anodization is performed to obtain a titanium substrate M3 loaded with a graded titanium dioxide nanotube array layer.

11. The titanium implant according to claim 10, wherein: The truncation treatment is to place the titanium substrate M1 in an aqueous solution and perform ultrasonic treatment, with an ultrasonic power of 200-300 W and an ultrasonic time of 10-15 minutes.

12. The titanium implant according to claim 10, wherein: The voltage of the secondary anodic oxidation is 10-15V, the temperature is 20-35°C, and the time is 30-50min.

13. The titanium implant according to claim 1, wherein: The piezoelectric material is selected from at least one of polymer piezoelectric materials, ceramic piezoelectric materials, and semiconductor piezoelectric materials.

14. The titanium implant according to claim 13, wherein: The polymer piezoelectric material is selected from at least one of PVDF, PVDF-TrFE, PHB, PLLA, PCL, PLGA, PHBV, collagen fiber, chitosan, cellulose and its derivatives, PVP, PVA, and PEO.

15. The titanium implant according to claim 13, wherein: The ceramic piezoelectric material is selected from at least one of barium titanate, potassium sodium niobate, potassium sodium lithium niobate, lithium niobate, strontium barium niobate, lead zirconate titanate, boron nitride, and hydroxyapatite.

16. The titanium implant according to claim 13, wherein: The semiconductor piezoelectric material is selected from at least one of CdS, CdSe, ZnO, ZnS, CdTe, ZnTe, GaAs, GaSb, InAs, InSb, and AlN.

17. The titanium implant according to claim 1, wherein: The mass concentration of the piezoelectric material in the piezoelectric suspension is 5-15wt%; The organic solvent is selected from at least one of dimethyl sulfoxide, dimethylformamide, dimethylacetamide, dichloromethane, acetonitrile, tetrahydrofuran, acetone, N-methylpyrrolidone, butyrolactone, phenol, m-phenol, caprolactam, sulfolane, and nitrobenzene.

18. The titanium implant according to claim 1, wherein: The humidity of the electrospinning is 20-30%, the temperature is 20-30°C, the ejection flow rate of the piezoelectric suspension is 0.5-2 mL / h, the spinning distance is 10-15 cm, the voltage applied to the piezoelectric suspension is 10-15 kV, and the voltage applied to the titanium substrate M3 is -10 to -3 kV.

19. Use of the titanium implant according to any one of claims 1 to 18 in the preparation of medical implant materials.

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