Titanium-based implant material with near-infrared light response piezoelectric coating on surface as well as preparation method and application of titanium-based implant material

Abstract

The invention belongs to the technical field of nano materials, and discloses a titanium-based implant material with a near-infrared light response piezoelectric coating on the surface and a preparation method and application of the titanium-based implant material. The method comprises the following steps: sequentially carrying out alkali heat treatment and hydrothermal treatment on a pretreated titanium-based implant material to obtain the titanium-based implant material with a barium titanate nanostructure on the surface; and compounding polypyrrole nanoparticles on the titanium-based implant material containing the barium titanate nanostructure on the surface through a chemical oxidation polymerization method to obtain the titanium-based implant material with the barium titanate / polypyrrole composite coating on the surface. The barium titanate / polypyrrole composite coating constructed by the method disclosed by the invention can respond to near-infrared light to realize good antibacterial performance, and meanwhile, can effectively promote osseointegration.

Description

Technical Field

[0001] The present invention belongs to the technical field of nanomaterials, and particularly relates to a titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface, a preparation method thereof, and an application thereof. Background Art

[0002] Titanium and its alloys are widely used in orthopedic implant products due to their unique medical applicability characteristics such as high specific strength, corrosion resistance, and biocompatibility. Medical titanium metal itself has no antibacterial property, and it is impossible to avoid the adhesion and proliferation of bacteria on the bone implant material and further form a bacterial biofilm, which is one of the main reasons for bone implant material-related infections. To prevent the failure of bone implant materials due to bacterial infection, it is very necessary to modify an antibacterial coating on the surface of medical titanium. By surface treatment of medical titanium metal or modification of a surface antibacterial coating to inhibit bacterial adhesion or kill bacteria, it has become an effective way to control implant-related infections. However, antibacterial agents such as antibiotics, silver, and antimicrobial peptides used in current research may cause problems such as antibiotic resistance or cytotoxicity, which will hinder the osteogenesis at the interface between the implant material and the surrounding bone tissue, leading to the failure of the implant surgery and unable to meet the clinical needs.

[0003] Therefore, ensuring the long-term, stable, efficient, controllable, and safe antibacterial effect of titanium-based bone implant materials is the current research focus. The phototherapy antibacterial strategy is considered a powerful means to deal with postoperative infections of bone implant materials due to its non-invasive nature, specific spatiotemporal selectivity, deep tissue penetration, and excellent biosecurity. Barium titanate (BTO) with good biocompatibility and piezoelectric properties has attracted wide attention and can promote the osteogenic differentiation of bone marrow mesenchymal stem cells by using the electric potential on its surface. However, BTO itself has no antibacterial property, so combining it with a light-responsive antibacterial agent may be a more promising strategy. Summary of the Invention

[0004] In order to overcome the above-mentioned disadvantages and deficiencies of the prior art, the primary object of the present invention is to provide a titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface.

[0005] Another object of the present invention is to provide a preparation method of the above-mentioned titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface.

[0006] A further object of the present invention is to provide an application of the above-mentioned titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface in the preparation of an implant for infectious bone defects.

[0007] The object of the present invention is achieved by the following solutions:

[0008] A titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface, which consists of a titanium-based implant material and a barium titanate / polypyrrole composite coating on the surface of the titanium-based implant material.

[0009] The preparation method of the above-mentioned titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface includes the following steps:

[0010] (1) Pretreatment: Clean and dry the titanium-based implant material to obtain the pretreated titanium-based implant material;

[0011] (2) Construction of barium titanate nanostructures: Place the pretreated titanium-based implant material obtained in step (1) in an alkali solution for alkali heat treatment, then place it in a barium hydroxide solution for hydrothermal treatment, wash and dry to obtain a titanium-based implant material containing barium titanate nanostructures;

[0012] (3) Construction of barium titanate / polypyrrole composite coating: Add pyrrole and the titanium-based implant material containing barium titanate nanostructures obtained in step (2) to a surfactant solution, stir, then add an oxidant for reaction, and dry to obtain a titanium-based implant material with a barium titanate / polypyrrole composite coating on its surface.

[0013] The titanium-based implant material described in step (1) is titanium and its alloys.

[0014] The cleaning in step (1) is to first perform ultrasonic cleaning and then clean the titanium-based implant material with a mixed acid of nitric acid and hydrofluoric acid.

[0015] The ultrasonic cleaning is specifically to perform ultrasonic cleaning with acetone, absolute ethanol and water in sequence, and the cleaning time for each time is 5 - 30 min.

[0016] The alkali solution described in step (2) is at least one of sodium hydroxide and potassium hydroxide solutions; the concentration of the alkali solution is 2 - 10 mol / L.

[0017] The concentration of the barium hydroxide solution described in step (2) is 0.01 - 0.5 mol / L.

[0018] The reaction temperature of the alkali heat treatment in step (2) is 25 - 200 °C, and the time is 4 - 20 h; the reaction temperature of the hydrothermal treatment is 100 - 300 °C, and the time is 6 - 24 h.

[0019] The surfactant described in step (3) is at least one of polyvinyl alcohol, dodecylbenzenesulfonic acid and sodium dodecyl sulfate; the concentration of the surfactant in the surfactant solution is 2 - 20 g / L.

[0020] The preparation of the surfactant solution described in step (3) includes: adding the surfactant to deionized water and stirring at 85 - 95 °C for 20 min - 60 min until the surfactant is dissolved.

[0021] The dosage of pyrrole described in step (3) satisfies that the concentration of pyrrole in the mixed solution during stirring is 0.01 - 0.5 mol / L.

[0022] The temperature of the solution when adding pyrrole in step (3) is 0 - 4 °C; the stirring time is 10 - 120 min.

[0023] The oxidant described in step (3) is one of ferric chloride and ammonium persulfate.

[0024] The dosage of the oxidant described in step (3) satisfies that the concentration of the oxidant in the mixed solution during the reaction is 0.01 - 0.3 mol / L.

[0025] The temperature of the solution when adding the oxidant in step (3) is 0 - 4 °C; the reaction time is 0.5 - 10 h.

[0026] Application of the above titanium-based implant material with a near-infrared light-responsive piezoelectric coating on the surface in the preparation of implant bodies for infectious bone defects.

[0027] Mechanism of the present invention:

[0028] The combination of BTO and polypyrrole (PPy) in the present invention is an effective modification strategy. Compared with general light-responsive antibacterial agents, PPy has advantages such as excellent light stability, high photothermal conversion efficiency, and conductivity. Using chemical oxidative polymerization to in-situ combine PPy on the surface of BTO can endow the implant material with good photothermal properties. The temperature change caused by light irradiation can trigger the release of charges by BTO with pyroelectric properties, and the combination of PPy with conductive properties is beneficial to the separation and transfer of charges.

[0029] The present invention has the following advantages and beneficial effects compared with the prior art:

[0030] (1) The present invention constructs a barium titanate / polypyrrole composite coating with near-infrared light-responsive piezoelectricity on the surface of the titanium implant material, which can effectively promote bone integration and achieve antibacterial function in response to near-infrared light.

[0031] (2) The barium titanate / polypyrrole composite material prepared by the present invention expands the light absorption of barium titanate, realizes more stable and efficient antibacterial, and has good biocompatibility.

[0032] (3) The preparation method of the present invention is simple, low-cost, and can be prepared on a large scale, overcomes the shortcomings and deficiencies of the prior art, and realizes a titanium implant material with intelligent regulation, precise repair, and simultaneous satisfaction of antibacterial and promotion of bone integration. Description of the Drawings

[0033] Figure 1Raman spectra of the titanium-based implant materials obtained in Example 1, Comparative Example 1 and Comparative Example 2.

[0034] Figure 2 SEM images of the titanium-based implant materials obtained in Example 1, Example 2 and Example 3

[0035] Figure 3 SEM images of the titanium-based implant materials obtained in Comparative Example 1 and Comparative Example 2.

[0036] Figure 4 Piezoelectric property diagrams of the titanium-based implant materials obtained in Example 1 and Comparative Example 1

[0037] Figure 5 Ultraviolet-visible-near-infrared absorption spectrum diagram of the titanium-based implant material obtained in Example 1.

[0038] Figure 6 Antibacterial result diagram of the titanium-based implant material obtained in Example 1.

[0039] Figure 7 Alizarin red S staining diagram of the titanium-based implant material obtained in Example 1. Detailed implementation manners

[0040] The present invention will be further described in detail below with reference to examples and drawings, but the implementation manners of the present invention are not limited thereto. For those not specified in the examples, they are carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments whose manufacturers are not specified, they are all conventional products that can be obtained through commercial purchase.

[0041] The reagents used in the examples can be conventionally purchased from the market without special instructions.

[0042] Example 1

[0043] (1) Pretreatment of the titanium-based implant material:

[0044] Titanium was ultrasonically cleaned with acetone, absolute ethanol and deionized water for 15 min respectively, then cleaned with a mixed acid of nitric acid and hydrofluoric acid, taken out and dried to obtain the pretreated titanium-based implant material;

[0045] (2) Construction of barium titanate nanostructures on the surface of titanium-based implant materials: Immerse the pretreated titanium-based implant materials obtained in step (1) in an 8 mol / L sodium hydroxide solution for alkali heat treatment. The reaction temperature for alkali heat treatment is 100 °C and the time is 24 h. After the reaction, take out and dry; then immerse the dried sample in a 0.05 mol / L barium hydroxide aqueous solution for hydrothermal treatment. The reaction temperature for hydrothermal treatment is 210 °C and the time is 8 h. After the reaction, take out and dry to obtain a barium titanate nanostructure coating on the surface of the titanium-based implant materials, and obtain the implant materials with barium titanate nanostructures on the surface;

[0046] (3) Construction of barium titanate / polypyrrole composite coatings on the surface of titanium-based implant materials:

[0047] Add polyvinyl alcohol to deionized water, heat to 90 °C, stir and dissolve for 30 min, where the concentration of polyvinyl alcohol is 12 g / L. Then, when the polyvinyl alcohol solution cools to 0 °C, add pyrrole to make the concentration of pyrrole in the solution 0.06 mol / L. Then add the barium titanate nanostructure implant materials obtained in step (2) to the solution and continue to react for 30 min. After that, add ferric chloride at 0 °C to make the concentration of ferric chloride in the solution 0.06 mol / L and continue to react for 2 h. Take out and dry to obtain a barium titanate / polypyrrole composite coating on the surface of the titanium-based implant materials, and obtain the titanium implant materials with barium titanate / polypyrrole composite coatings on the surface.

[0048] Example 2

[0049] The preparation method of Example 2 is basically the same as that of Example 1. The only difference is that after adding pyrrole in step (3), the concentration of pyrrole in the solution is 0.02 mol / L. Example 2 prepared a titanium implant material with a barium titanate / polypyrrole composite coating on the surface.

[0050] Example 3

[0051] The preparation method of Example 3 is basically the same as that of Example 1. The only difference is that after adding pyrrole in step (3), the concentration of pyrrole in the solution is 0.1 mol / L. Example 3 prepared a titanium implant material with a barium titanate / polypyrrole composite coating on the surface.

[0052] Comparative Example 1

[0053] (1) Pretreatment of titanium-based implant materials:

[0054] Ultrasonically clean titanium with acetone, absolute ethanol and deionized water for 20 min respectively, and then clean with a mixed acid of nitric acid and hydrofluoric acid. Take out and dry to obtain the pretreated titanium-based implant materials;

[0055] (2) Construction of barium titanate nanostructures on the surface of titanium-based implant materials: Immerse the pretreated titanium-based implant materials obtained in step (1) in an 8 mol / L sodium hydroxide solution for alkali heat treatment. The reaction temperature for the alkali heat treatment is 100 °C and the time is 20 h. After the reaction, take out and dry. Then immerse the dried sample in a 0.08 mol / L barium hydroxide aqueous solution for hydrothermal treatment. The reaction temperature for the hydrothermal treatment is 210 °C and the time is 6 h. After the reaction, take out and dry to obtain a barium titanate nanostructure coating on the surface of the titanium-based implant materials, and obtain the implant materials with barium titanate nanostructures on the surface.

[0056] Comparative Example 2

[0057] (1) Pretreatment of titanium-based implant materials:

[0058] Ultrasonically clean titanium with acetone, absolute ethanol and deionized water for 20 min respectively, then clean with a mixed acid of nitric acid and hydrofluoric acid, take out and dry to obtain the pretreated titanium-based implant materials;

[0059] (2) Construction of polypyrrole coatings on the surface of titanium-based implant materials

[0060] Add polyvinyl alcohol to deionized water, heat to 90 °C and stir to dissolve for 40 min, where the concentration of polyvinyl alcohol is 12 g / L. Then when the polyvinyl alcohol solution cools to 2 °C, add pyrrole to make the concentration of pyrrole in the solution 0.06 mol / L. Then add the pretreated titanium-based implant materials obtained in step (1) to the solution and continue to react for 30 min. Then add ferric chloride at 0 °C to make the concentration of ferric chloride in the solution 0.06 mol / L and continue to react for 2 h. Take out and dry to obtain a polypyrrole composite coating on the surface of the titanium-based implant materials, and obtain the titanium implant materials with polypyrrole composite coatings on the surface.

[0061] In the following tests, the meanings of each group are as follows:

[0062] Ti: Pretreated titanium-based implant materials in step (1) of Example 1

[0063] Ti-BTO: Implant materials with barium titanate nanostructures on the surface obtained in Comparative Example 1

[0064] Ti-PPy: Titanium implant materials with polypyrrole composite coatings on the surface obtained in Comparative Example 2

[0065] Ti-BTO-PPy: Titanium implant materials with barium titanate / polypyrrole composite coatings on the surface obtained in Example 1

[0066] Test Example 1

[0067] Figure 1These are the Raman spectra of each group of materials. Analysis reveals that there are no characteristic peaks shown on the surface of the Ti group, while the Ti-BTO group samples exhibit typical peaks of inorganic barium titanate (BTO) at 185, 302, 515, and 715 cm -1 The Ti-PPy and Ti-BTO-PPy groups after polypyrrole (PPy) treatment both show typical PPy peaks at 928, 976, 1045, 1330, and 1580 cm -1 These peaks respectively represent the out-of-plane deformation vibration peak of poly C-H, the in-plane deformation vibration peak of the pyrrole ring, the in-plane deformation vibration peak of C-H, the stretching vibration peak of the pyrrole ring, and the C═C vibration peak, which proves the successful preparation of the Ti-BTO, Ti-PPy, and Ti-BTO-PPy materials.

[0068] Figure 2 shows that with the increase in the concentration of pyrrole (Py), the PPy nanoparticles grafted on the surface of BTO gradually increase. Grafting PPy nanoparticles on the surface of BTO can endow the material with near-infrared light response ability, have good photothermal properties, and at the same time, the PPy nanoparticles with good conductivity are beneficial to transfer the charges on the surface of BTO to the surface of PPy. Among them, the partial coverage of PPy on BTO in Example 1 is more conducive to improving the biocompatibility of the material.

[0069] Figure 3 It is observed that BTO nanocolumns with a diameter of about 100 nm grow on the surface of the Ti-BTO material; the surface of the Ti-PPy material is a film layer deposited with PPy nanoparticles.

[0070] Figure 4 are the phase curves and amplitude curves of Ti-BTO and Ti-BTO-PPy. The phase curve of Ti-BTO shows a significant hysteresis loop and a phase switching with a maximum interval of 180°. The amplitude butterfly curve also proves its good piezoelectric performance. After grafting PPy nanoparticles on the surface of the BTO nanorod array, it also has good piezoelectric performance.

[0071] Figure 5 are the ultraviolet-visible-near-infrared absorption spectra of different materials. It can be found that the absorption ability of Ti-BTO-PPy for near-infrared light is greatly improved compared with Ti, which lays a foundation for the antibacterial performance of the subsequent materials.

[0072] Test Example 2

[0073] Antibacterial experiments were carried out using Escherichia coli and Staphylococcus aureus as indicator bacteria. The specific experiment includes: putting the sterilized materials into a 48-well plate, and then adding 500 μL of 10 6CFU / mL bacterial solution. Then, the light irradiation group (NIR) was immediately irradiated with near-infrared light at a wavelength of 808 nm for 10 min, diluted (100 times), and spread on LB agar solid medium. After culturing at 37 °C for 24 h, the viable bacteria count was statistically analyzed according to the plate colony counting method. Five parallel samples were set in each group, and the average value was taken. Each experiment was repeated three times.

[0074] From Figure 6 It can be seen that the experimental group showed good antibacterial performance. By calculating the colony number of each group, the conclusion was drawn that under dark conditions, neither Ti-BTO-PPy nor Ti showed antibacterial properties. However, under light irradiation conditions, Ti-BTO-PPy showed an antibacterial rate of 99% against Staphylococcus aureus and 96% against Escherichia coli. This indicates that the barium titanate / polypyrrole nanostructure itself has no significant effect on destroying or promoting the proliferation of bacteria. Under near-infrared light irradiation conditions, Ti-BTO-PPy showed excellent antibacterial performance against Staphylococcus aureus and Escherichia coli.

[0075] Test Example 3

[0076] The osteoblast mineralized nodule staining kit (alizarin red S method) was used to stain the calcium in the osteoblast mineralized nodules to evaluate the degree of osteogenic differentiation of BMSCs on the sample surface. From Figure 7 It was observed that the calcium nodules stained on the surface of the Ti-BTO-PPy group showed black-red and were distributed in blocks, while the surface of the Ti group showed a relatively uniform dark red, indicating that the Ti-BTO-PPy material had good osteogenic performance.

[0077] The above embodiments are preferred embodiments of the present invention. However, the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface, characterized in that: It consists of a titanium-based implant material and a barium titanate / polypyrrole composite coating on the surface of the titanium-based implant material.

2. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface as described in claim 1, characterized in that it includes the following steps: (1) Construction of barium titanate nanostructures: Place the pretreated titanium-based implant material in an alkali solution for alkali heat treatment, then place it in a barium hydroxide solution for hydrothermal treatment, wash and dry to obtain a titanium-based implant material containing barium titanate nanostructures; (2) Construction of barium titanate / polypyrrole composite coating: Add pyrrole and the titanium-based implant material containing barium titanate nanostructures described in step (2) to a surfactant solution, stir, then add an oxidant to react, and dry to obtain a titanium-based implant material with a barium titanate / polypyrrole composite coating on its surface.

3. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The alkali solution in step (1) is at least one of sodium hydroxide and potassium hydroxide solutions; the concentration of the alkali solution is 2 - 10 mol / L; The concentration of the barium hydroxide solution in step (1) is 0.01 - 0.5 mol / L.

4. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The reaction temperature of the alkali heat treatment in step (1) is 25 - 200 °C, and the time is 4 - 20 h; the reaction temperature of the hydrothermal treatment is 100 - 300 °C, and the time is 6 - 24 h.

5. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The surfactant in step (2) is at least one of polyvinyl alcohol, dodecylbenzenesulfonic acid, and sodium dodecyl sulfate; the concentration of the surfactant in the surfactant solution is 2 - 20 g / L.

6. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The dosage of pyrrole in step (2) satisfies: the concentration of pyrrole in the mixed solution during stirring is 0.01 - 0.5 mol / L.

7. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The solution temperature when adding pyrrole in step (2) is 0 - 4 °C; the stirring time is 10 - 120 min.

8. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The oxidant in step (2) is one of ferric chloride and ammonium persulfate.

9. The preparation method of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on its surface according to claim 2, characterized in that: The dosage of the oxidant in step (2) satisfies: the concentration of the oxidant in the mixed solution during the reaction is 0.01 - 0.3 mol / L; The solution temperature when adding the oxidant in step (2) is 0 - 4 °C; the reaction time is 0.5 - 10 h.

10. Use of the titanium-based implant material with a near-infrared light-responsive piezoelectric coating on the surface as claimed in claim 1 in the preparation of an implant for infectious bone defects.

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