Sodium niobate / molybdenum diselenide heterojunction and preparation method and application thereof

Abstract

The invention discloses a sodium niobate / molybdenum diselenide heterojunction and a preparation method and application thereof. The invention provides a sodium niobate / molybdenum diselenide heterojunction which comprises manganese-doped sodium niobate and molybdenum diselenide, and the ion molar ratio of Nb to Mo in the manganese-doped sodium niobate and molybdenum diselenide is 1.5: (0.5-3). The doped sodium niobate / molybdenum diselenide heterojunction has high piezoelectric performance and sonodynamic performance and has enzyme-like activity, under high-power ultrasonic driving, the sonodynamic and enzyme-like activity of the material is enhanced through the piezoelectric effect of the material, multiple ROS are generated, bacteria are killed in a synergistic mode, and biological membranes are removed; under the driving of low-power ultrasonic waves, oxidative stress materials are relieved, osteoblasts are proliferated and differentiated, and potential application prospects are achieved in the aspect of treating infectious bone tissues.

Description

Technical Field

[0001] This invention relates to a sodium niobate / molybdenum diselenide heterojunction, its preparation method, and its uses. Background Technology

[0002] Treatment of infected bone defects is a lengthy and complex process, requiring both control of the infection and repair of the defect, which has always been a challenge in orthopedics. Infectious bone defects caused by bacteria are often insidious and difficult to treat. Bacterial proliferation and biofilm formation can reduce osteoblast activity and hinder bone defect repair. Therefore, treating bacterial infection and promoting bone tissue regeneration are crucial for the repair of infected bone defects.

[0003] Studies have shown that excessive reactive oxygen species (ROS) in the bone tissue repair microenvironment can also damage osteocytes and inhibit bone regeneration. Therefore, endowing materials with antioxidant activity to eliminate excess ROS and alleviate oxidative stress during bone tissue regeneration is crucial. Constructing a microenvironment conducive to osteoblasts is essential. Furthermore, numerous studies have shown that electrical stimulation, through piezoelectric gating of Ca²⁺… 2+ Channel proteins regulate the expression of osteogenic genes, enhance osteoblast responses, and promote bone regeneration. Therefore, endowing bioactive materials with antioxidant and mechano-electrical responsive properties is crucial for accelerating bone tissue regeneration. Consequently, there is an urgent need to develop novel materials that combine piezoelectric properties, enzyme-like activity, sonodynamic properties, and biocompatibility for the treatment of infected bone defects. However, selecting suitable piezoelectric materials and modifying them to obtain biocompatible and suitable bone repair materials remains a challenge.

[0004] Acousto-piezoelectric dynamics therapy (SPT) is a novel antibacterial strategy that couples piezoelectric materials with ultrasound. Under the pressure triggering of ultrasound, non-centrosymmetric piezoelectric acoustic sensitizers can induce band bending by generating an internal electric field, driving charge transfer to the surrounding medium, further promoting electron-hole pair separation, and reacting with oxygen (O2) and (H2O) to produce more reactive oxygen species (ROS). Transition metal nanozymes, due to their ability to interconvert the valence states of metal ions (e.g., Mn2+, 22-, 24 ... 2+ / M n3+ / Mn 4+ Mo 4+ / Mo 6+ Nanozymes exhibit diverse enzyme activities due to their pH responsiveness and are widely used in chemokinetic therapy (CDT). The external electric field generated by ultrasound-triggered piezoelectric response has been shown to accelerate the rapid movement and separation of electrons (valence state transitions of ions), further enhancing nanozyme activity. During tissue repair, reconstructing the physiological electrical microenvironment of defect sites using piezoelectric materials is an effective strategy for repairing bone defects. Furthermore, the introduction of bioactive piezoelectric materials can synergistically release bioactive ions (such as niobium and molybdenum ions), thereby promoting bone tissue regeneration.

[0005] Sodium niobate (NaNbO3) is a kind of piezoelectric semiconductor with perovskite structure, but the wide band gap (about 3.4 eV) makes the carrier migration rate low and the electron-hole separation difficult, which seriously reduces the generation of active oxygen. Ion doping engineering reduces the energy required for electrons to jump from the valence band to the conduction band by reducing the band gap, making it easier to generate electrons under ultrasonic excitation and promoting the generation of active oxygen. Ion doping engineering also improves piezoelectric performance by creating lattice defects and introducing oxygen vacancy defects to promote more efficient charge separation, promote ROS generation and confer enzyme activity. Two-dimensional (2D) piezoelectric semiconductor nanomaterials have attracted widespread attention in the field of catalysis due to their large surface area, high active site, good biocompatibility and other advantages. Heterojunction engineering promotes interface charge transfer by establishing an internal electric field (IEF) at the interface, driving electron and hole separation. And the piezoelectric polarization electric field (PEF) formed by ultrasonic triggering of the heterojunction can enhance the internal electric field, resulting in band bending, reducing the redox energy barrier, achieving efficient electron-hole separation and improving SPT performance. In addition, oxygen vacancy engineering can improve the microenvironment and local electronic structure of the heterojunction interface, forming a tight interface connection. The traps induced by it effectively control the charge separation and trigger a fast charge transport channel on the heterojunction interface, improving the efficiency of charge separation and further improving the SPT performance. And oxygen vacancy engineering can produce unpaired electrons in the crystal and act as active sites to participate in the reaction, reducing the activation energy of the reaction, thereby enhancing enzyme activity. SUMMARY

[0006] To solve the above technical problems, the present application provides a sodium niobate / molybdenum diselenide heterojunction and a preparation method and use thereof. The manganese-doped sodium niobate / molybdenum diselenide heterojunction of the present application has strong piezoelectric performance and sonodynamic performance, and has enzyme-like activity. Under the drive of high-power ultrasonic waves, the piezoelectric effect of the material enhances the sonodynamic and enzyme-like activity of the material, generates multiple ROS, cooperatively kills bacteria and removes biofilms; under the drive of low-power ultrasonic waves, the material relieves oxidative stress and promotes osteoblast proliferation and differentiation, and has potential application prospects in the treatment of infected bone tissue.

[0007] The first aspect of the present application provides a sodium niobate / molybdenum diselenide heterojunction comprising manganese-doped sodium niobate and molybdenum diselenide, wherein the ionic molar ratio of Nb to Mo in the manganese-doped sodium niobate and molybdenum diselenide is 1.5: (0.5-3).

[0008] In an embodiment, the ionic molar ratio of Nb to Mo in the manganese-doped sodium niobate is 1.5: (0.5-2); for example, 1.5:1.5.

[0009] In an embodiment, the molar ratio of manganese to niobium in the manganese-doped sodium niobate of the sodium niobate / molybdenum diselenide heterojunction is x:(100-x); 0

[0010] In an embodiment, the sodium niobate / molybdenum diselenide heterojunction is a composite structure of two semiconductors.

[0011] The manganese-doped sodium niobate is a wide-bandgap semiconductor, preferably having a bandgap of 2.5-3.0 eV.

[0012] The molybdenum diselenide is a narrow-bandgap semiconductor, preferably having a bandgap of 1.2-1.7 eV.

[0013] In an embodiment, the surface of the manganese-doped sodium niobate of the sodium niobate / molybdenum diselenide heterojunction has molybdenum diselenide; the particle size of the molybdenum diselenide is preferably 25-75 nm; more preferably 35-55 nm.

[0014] In an embodiment, the particle size of the manganese-doped sodium niobate can be 100-350 nm, more preferably 170-230 nm.

[0015] In an embodiment, the particle size of the sodium niobate / molybdenum diselenide heterojunction can be 200-450 nm, preferably 250-350 nm.

[0016] In an embodiment, the sodium niobate / molybdenum diselenide heterojunction has a heterojunction interface between the manganese-doped sodium niobate and the molybdenum diselenide.

[0017] The lattice spacing on the side of the manganese-doped sodium niobate is preferably 0.35-0.5 nm, more preferably 0.39-0.41 nm.

[0018] The lattice spacing on the side of the molybdenum diselenide is preferably 0.55-0.7 nm, more preferably 0.64-0.66 nm.

[0019] In an embodiment, the d 33 is about 150-250 pm / V; for example, 180-200 pm / V.

[0020] In an embodiment, the acoustoelectric current density of the manganese-doped sodium niobate is 1.4-2.5 μA / cm 2 , for example, 2.00-2.20 μA / cm 2 .

[0021] The second aspect of the application provides a manganese-doped sodium niobate, wherein the molar ratio of manganese to niobium is x:(100-x); 0

[0022] In one embodiment, the molar ratio of manganese to niobium is x:(100-x); 1

[0023] In one embodiment, the particle size of the manganese-doped sodium niobate is 100-350 nm, preferably 170-230 nm.

[0024] In one embodiment, the total molar percentage of manganese doping is >0% to <6%; preferably >1% to <5%; for example >3% to <5%; preferably 4%.

[0025] In one embodiment, the manganese-doped sodium niobate is a wide band gap semiconductor, preferably with a band gap of 2.5-3.0 eV.

[0026] In one embodiment, the acoustoelectric current density of the manganese-doped sodium niobate is 1.4-2.5 μA / cm 2 , for example 2.00-2.20 μA / cm 2 .

[0027] In one embodiment, the manganese-doped sodium niobate is a square crystal.

[0028] The third aspect of the present application provides a method for preparing the aforementioned manganese-doped sodium niobate, comprising the following steps:

[0029] reacting a sodium source, a manganese source and a niobium source to obtain the manganese-doped sodium niobate; wherein the molar ratio of manganese to niobium in the sodium source, the manganese source and the niobium source is x:(100-x); 0

[0030] In one embodiment, the molar ratio of manganese to niobium is x:(100-x); 1

[0031] In one embodiment, the molar ratio of sodium to niobium in the sodium source and the niobium source is (10-60):1, for example (13-54):1; further for example 13.33:1 or 53.33:1.

[0032] In one embodiment, the sodium source is sodium oxalate, sodium phosphate, sodium carbonate, sodium nitrate, sodium acetate, NaOH, a NaOH solution or NaCl; preferably a NaOH solution; for example an aqueous NaOH solution with a concentration of 1-10 mol / L.

[0033] In one embodiment, the manganese source is Mn(NO3)3.

[0034] In one embodiment, the niobium source is a niobium alkoxide, Nb2O5 or potassium niobate; the niobium alkoxide can be pentaethoxy niobium; preferably Nb2O5.

[0035] In an embodiment, the preparation method is a solid phase reaction method, a sol-gel method (wet chemical method), a hydrothermal synthesis method, a molten salt method or a co-precipitation method; preferably a hydrothermal synthesis method.

[0036] In an embodiment, when the preparation method is a hydrothermal synthesis method, it comprises the following steps:

[0037] The mixture of the sodium source, the manganese source and the niobium source is reacted under heating and pressurization to obtain the manganese-doped sodium niobate;

[0038] Preferably, at least one of the following conditions is met:

[0039] (1) the temperature of the heating is 120-200°C, preferably 160°C;

[0040] (2) the pressure of the pressurization is 0.1-0.5 MPa; preferably 0.1013 MPa;

[0041] (3) after the reaction, the following post-treatment steps are included:

[0042] After the reaction under heating and pressurization, washing and ultrasonic treatment are performed, and the fine particle dispersion liquid is taken from the upper layer; the fine particle dispersion liquid is centrifuged to obtain the precipitate, which is dried to obtain the manganese-doped sodium niobate;

[0043] The washing is performed multiple times using deionized water and anhydrous ethanol;

[0044] The ultrasonic treatment is preferably performed in water;

[0045] The ultrasonic treatment time is preferably 10-40 min, for example 30 min;

[0046] The ultrasonic treatment temperature is preferably room temperature;

[0047] The ultrasonic treatment frequency is preferably 40 kHz;

[0048] The centrifugation frequency is preferably 6000-9000 rpm, for example 8000 rpm;

[0049] The centrifugation time is preferably 3-7 min, for example 5 min;

[0050] The drying temperature is 40-80°C, for example 60°C; and the drying pressure is normal pressure;

[0051] After the drying, the following steps are preferably included:

[0052] The manganese-doped sodium niobate is pressed and subjected to corona polarization;

[0053] The pressing is preferably pressing the manganese-doped sodium niobate into a 0.5-1.5 cm disc per 0.2 g; more preferably a 1 cm disc;

[0054] The voltage of the corona polarization is 3-5 kv, for example 3.5 kv;

[0055] The sodium source is NaOH solution, preferably 1-10 mol / L NaOH aqueous solution;

[0056] The niobium source is Nb2O5;

[0057] The manganese source is Mn(NO3)3.

[0058] The fourth aspect of the present application provides a manganese-doped sodium niobate prepared by the aforementioned method, preferably, the manganese-doped sodium niobate is as aforementioned.

[0059] The fifth aspect of the present application provides a preparation method of the aforementioned sodium niobate / molybdenum diselenide heterojunction, which comprises the following steps:

[0060] Mixing the aforementioned Na2MoO4·2H2O, SeO2 and hydrazine hydrate, and drying, calcining after heating reaction of the aforementioned manganese-doped sodium niobate, to obtain the sodium niobate / molybdenum diselenide heterojunction; wherein the molar ratio of the Na2MoO4·2H2O, the SeO2, the hydrazine hydrate and the manganese-doped sodium niobate is 1.5:3:(0.15):(0.5-3);

[0061] Preferably, at least one of the following conditions is met:

[0062] (1) The molar ratio of the Na2MoO4·2H2O, the SeO2, the hydrazine hydrate and the manganese-doped sodium niobate is 1.5:3:(0.15):(0.5-2); for example 1.5:3:(0.15):1.5;

[0063] (2) The mixing time is 10-14 h, for example 12 h;

[0064] (3) The heating temperature is 120-250°C, preferably 200°C;

[0065] (4) The heating can be heating in a stainless steel hydrothermal reaction kettle with a polytetrafluoroethylene inner liner;

[0066] (5) The heating time can be 8-30 hours, for example 24 hours;

[0067] (6) The heating further comprises a washing step, and the washing is washing multiple times with deionized water and anhydrous ethanol;

[0068] The drying is performed at a temperature of 40-80℃, for example 60℃, and at normal pressure.

[0069] (7) The calcination is performed under an argon atmosphere;

[0070] (8) The calcination is performed at a temperature of 400-600℃, for example 500℃;

[0071] (9) The calcination is performed for 1-3h, for example 2h;

[0072] (10) The calcination is performed under an argon atmosphere at a temperature of 500℃ for 2h.

[0073] The sixth aspect of the present application provides a sodium niobate / molybdenum diselenide heterojunction prepared by the aforementioned preparation method.

[0074] The seventh aspect of the present application provides a use of manganese-doped sodium niobate and a sodium niobate / molybdenum diselenide heterojunction as a bone repair material; the manganese-doped sodium niobate is as described above, and the sodium niobate / molybdenum diselenide heterojunction is as described above.

[0075] The eighth aspect of the present application provides a use of a sodium niobate / molybdenum diselenide heterojunction as a bone repair material; the manganese-doped sodium niobate is as described above, and the sodium niobate / molybdenum diselenide heterojunction is as described above.

[0076] In an embodiment, the manganese-doped sodium niobate has a percentage of oxygen vacancies of 18-21%, for example 20.92%; the percentage of oxygen vacancies = content of oxygen vacancies / (content of oxygen vacancies + content of lattice oxygen + content of adsorbed oxygen) × 100%.

[0077] In an embodiment, the sodium niobate / molybdenum diselenide heterojunction preferably has the diffraction peaks of the aforementioned manganese-doped sodium niobate and the aforementioned molybdenum diselenide.

[0078] In an embodiment, the micro-morphology of the sodium niobate / molybdenum diselenide heterojunction is detected by electron microscopy and transmission electron microscopy.

[0079] In an embodiment, the micro-morphology of the sodium niobate / molybdenum diselenide heterojunction satisfies one or more of the following conditions:

[0080] (1) The manganese-doped sodium niobate in-situ grows the molybdenum diselenide;

[0081] (2) There is a heterojunction interface between the manganese-doped sodium niobate and the molybdenum diselenide;

[0082] (3) The manganese-doped sodium niobate side of the sodium niobate / molybdenum diselenide heterojunction has a lattice spacing of 0.402nm;

[0083] (4) The sodium niobate / molybdenum diselenide heterojunction has a lattice spacing of 0.650 nm on the molybdenum diselenide side.

[0084] In an embodiment, the manganese-doped sodium niobate and the sodium niobate / molybdenum diselenide heterojunction are tested for sonodynamic performance using Rhodamine B assay, with the following specific test conditions:

[0085] Ultrasonic irradiation, with parameters of 1 MHz, 1.5 W / cm 2 , and a RhB aqueous solution concentration of 10 mg / L, 500 μg / mL of the sodium niobate / molybdenum diselenide heterojunction is added to the RhB aqueous solution; another group has 250 ug / mL of the manganese-doped sodium niobate added to the RhB aqueous solution; after 5 minutes of ultrasonic irradiation, the supernatant is taken by centrifugation, and the absorbance of the supernatant at 550 nm is measured using a UV spectrophotometer;

[0086] wherein the RhB absorbance of the manganese-doped sodium niobate is 0.09;

[0087] The RhB absorbance of the sodium niobate / molybdenum diselenide heterojunction is 0.03.

[0088] In an embodiment, the manganese-doped sodium niobate and the sodium niobate / molybdenum diselenide heterojunction are tested for POD-like enzyme activity, with the following specific test conditions:

[0089] POD-like activity of the particles is determined in the presence of H2O2 (30 mM) using 3,3',5,5'-tetramethylbenzidine (1.2 mM) as a substrate; TMB aqueous solution (pH=5.5); 500 μg / mL of the sodium niobate / molybdenum diselenide heterojunction is added to the TMB aqueous solution; another group has 250 ug / mL of the manganese-doped sodium niobate added to the TMB aqueous solution; after 10 minutes of reaction under ultrasonic irradiation (1.5 W / cm 2 , 1 MHz, 50% duty cycle) or without ultrasonic irradiation, the supernatant is taken by centrifugation, and the absorption spectrum is determined using a UV-vis-NIR;

[0090] wherein the TMB absorbance of the manganese-doped sodium niobate without ultrasonic irradiation is 0.49;

[0091] The TMB absorbance of the sodium niobate / molybdenum diselenide heterojunction without ultrasonic irradiation is 1.13;

[0092] The TMB absorbance of the sodium niobate / molybdenum diselenide heterojunction under ultrasonic irradiation is 1.61.

[0093] In an embodiment, the manganese-doped sodium niobate and the sodium niobate / molybdenum diselenide heterojunction are determined for CAT-like enzyme activity, and the specific test conditions are as follows:

[0094] The 250 ug / mL manganese-doped sodium niobate is immersed in a 50 mL aqueous solution containing 100 mM H2O2; or the 500 ug / mL sodium niobate / molybdenum diselenide heterojunction is immersed in a 50 mL aqueous solution containing 100 mM H2O2; the pH of the solution is adjusted using hydrochloric acid (0.1 mol), pH = 7.4, and the dissolved oxygen content (mg / L) is detected at different times (every 5 min within 1 h) using a dissolved oxygen meter to verify the CAT-like enzyme activity; the detection is carried out under ultrasonic irradiation (1 MHz, 0.5 W / cm 2 ) or without ultrasonic irradiation;

[0095] The oxygen production concentration of the manganese-doped sodium niobate under the condition of no ultrasonic irradiation is 9.3 mg / L;

[0096] The oxygen production concentration of the sodium niobate / molybdenum diselenide heterojunction under the condition of no ultrasonic irradiation is 7.9 mg / L;

[0097] The oxygen production concentration of the sodium niobate / molybdenum diselenide heterojunction under the condition of ultrasonic irradiation is 9.8 mg / L.

[0098] In an embodiment, the in vitro antibacterial performance of the sodium niobate / molybdenum diselenide heterojunction is determined, and the specific test method is as follows:

[0099] The sodium niobate / molybdenum diselenide heterojunction is co-cultured with S. aureus, and the antibacterial ratio is determined by colony counting method, and the sample is sterilized by ultraviolet irradiation for 12 h. The bacterial suspension (1 mL) with a concentration of 1×10 6 CFU / mL is co-cultured with the sample (500 ug / mL) in a 24-well plate for 24 hours: for the H2O2 group, 1 mM H2O2 is added to each group. For the US group, each group is ultrasonically irradiated for 15 min (1.5 W / cm 2 , 1 MHz, 50% duty cycle). After 6 h of continuous co-culture, subsequent tests are carried out. The bacterial suspension after culture is diluted 10 times, and the bacterial suspension (20 uL) is spread on a nutrient agar plate, which is incubated at 37°C for 24 h, and then photographed and counted. The antibacterial rate calculation formula: Antibacterial ratio (%) = (C-S) / S, wherein C and S are the number of colonies of the Control group and the sample group, respectively; the Control group is a reference group without the addition of the sodium niobate / molybdenum diselenide heterojunction;

[0100] The antibacterial rate of the Control group is 3.5%.

[0101] The antibacterial rate of the sodium niobate / molybdenum diselenide heterojunction is 27.84%;

[0102] The antibacterial rate of the sodium niobate / molybdenum diselenide heterojunction added with H2O2 is 83.48%;

[0103] The antibacterial rate of the sodium niobate / molybdenum diselenide heterojunction after ultrasonic irradiation is 86.69%;

[0104] The antibacterial rate of the sodium niobate / molybdenum diselenide heterojunction after ultrasonic irradiation and added with H2O2 is 99.32%.

[0105] In an embodiment, the cell viability of the sodium niobate / molybdenum diselenide heterojunction is determined, and the specific test conditions are as follows:

[0106] The cell culture method is as follows: the cells used are rat bone marrow mesenchymal stem cells (rBMSCs), and the specific cell culture is as follows: the rBMSCs are cultured in aMEM medium added with 10% fetal bovine serum and 1% penicillin / streptomycin, the incubator is set to 37°C, 5% CO2 atmosphere, the medium is replaced every 2 days, and the rBMSCs of 3-5 generations are used for cell experiments;

[0107] The cell viability test conditions are as follows: the US power is 1 MHz, 0.5 W / cm 2 , 20 seconds / time, 3 times / day. After the cells adhere, the cell culture medium is replaced with a culture medium containing 100 μM of H2O2 for one day, and then the cells are cultured with the sample for 1d and 3d, after which the culture medium is removed, and the CCK-8 is used to detect the proliferation of the cells on the sample;

[0108] The cell viability of the sodium niobate / molybdenum diselenide heterojunction added with H2O2 is 89.67%;

[0109] The cell viability of the sodium niobate / molybdenum diselenide heterojunction after ultrasonic irradiation and added with H2O2 is 96.42%.

[0110] In an embodiment, the ROS scavenging ability of the sodium niobate / molybdenum diselenide heterojunction in cells is determined, and the specific cell culture method is as described above, and further comprising the following steps: after co-culturing for 1d, the culture medium is removed, and the sample is stained with DCFH-HA fluorescent probe for intracellular ROS. The CLSM is used to observe the stained cells. The ROS fluorescence intensity is quantitatively analyzed by Image J software;

[0111] The relative fluorescence intensity of the sodium niobate / molybdenum diselenide heterojunction added with H2O2 is 4192.70 a.u;

[0112] The relative fluorescence intensity of the sodium niobate / molybdenum diselenide heterojunction after adding H2O2 and ultrasonic irradiation is 1257.11 a.u.

[0113] In an embodiment, the effect of the sodium niobate / molybdenum diselenide heterojunction on the osteogenic differentiation of rBMSCs is determined, and the specific cell culture method is as described above, and the specific determination method is as follows: alkaline phosphatase (ALP) staining and ALP activity quantitative analysis are used to evaluate the early osteogenic differentiation of cells. After the cells are cultured with the sample for 14 d, the cells are fixed with 4% paraformaldehyde, the cells on the sample are stained with an alkaline phosphatase color developing kit, the staining condition on the 7th day is observed under an optical microscope, in order to quantitatively analyze the ALP activity, 1% Nonidet P-40 solution is added to the hole plate to lyse the cells for 1 h, and centrifugation (2000 rpm) is performed for 10 min. After treatment with an alkaline phosphatase detection kit, the absorbance (OD value) of the solution is determined at 405 nm by using an enzyme-labeled instrument. The total protein amount is determined by using a BCA protein determination kit, and the ALP activity is calculated according to the absorbance at 405 nm divided by the total protein amount;

[0114] The ALP activity of the sodium niobate / molybdenum diselenide heterojunction after adding H2O2 is 6.72 (IU / g);

[0115] The ALP activity of the sodium niobate / molybdenum diselenide heterojunction after adding H2O2 and ultrasonic irradiation is 7.42 (IU / g).

[0116] In an embodiment, the late osteogenic differentiation performance of the sodium niobate / molybdenum diselenide heterojunction is determined, and the specific cell culture method is as described above, and the method further comprises the following steps: after the cells are cultured with the sample for 21 d, the cells are fixed with 4% PA, the cells on the sample are stained with 1% ARS solution, and the staining condition on the 21st day is observed under an optical microscope. In order to quantitatively analyze the ARS, the sample is soaked in a 10% cetylpyridinium chloride solution for 1 h, and the absorbance of the solution is determined at 620 nm:

[0117] The ARS absorbance of the sodium niobate / molybdenum diselenide heterojunction after adding H2O2 is 0.621;

[0118] The ARS absorbance of the sodium niobate / molybdenum diselenide heterojunction after adding H2O2 and ultrasonic irradiation is 0.836.

[0119] In an embodiment, the intracellular Ca2+ content of the sodium niobate / molybdenum diselenide heterojunction is determined, and the specific cell culture method is as described above, and the method further comprises the following steps of determining by using a Fluo-4 probe: 2+

[0120] ​The relative fluorescence intensity of the sodium niobate / molybdenum diselenide heterojunction added with H2O2 is 5876.29 a.u.

[0121] The relative fluorescence intensity of the sodium niobate / molybdenum diselenide heterojunction added with H2O2 and ultrasonically irradiated is 11463.25 a.u.

[0122] On the basis of common general knowledge in the art, the above-mentioned preferred conditions can be combined arbitrarily, thereby obtaining various preferred examples of the present application.

[0123] The reagents and raw materials used in the present application are commercially available.

[0124] The positive progress effect of the present application is that the doped sodium niobate / molybdenum diselenide heterojunction has strong piezoelectric properties and acoustic power properties, and has enzyme-like activity. Under the driving of high-power ultrasonic waves, the piezoelectric effect of the material enhances the acoustic power and enzyme-like activity of the material, generates various ROS, cooperatively kills bacteria and removes biofilm; under the driving of low-power ultrasonic waves, relieves oxidative stress materials and promotes osteoblast proliferation and differentiation, and has potential application prospects in the treatment of infected bone tissue. BRIEF DESCRIPTION OF DRAWINGS

[0125] Figure 1 SEM image of NNO prepared for Example 1

[0126] Figure 2 SEM image of MNNO2 prepared for Example 1

[0127] Figure 3 SEM image of MNNO prepared for Example 1

[0128] Figure 4 SEM image of MNNO6 prepared for Example 1

[0129] Figure 5 Electrochemical impedance spectrogram of NNO, MNNO2, MNNO, MNNO6 prepared for Example 1.

[0130] Figure 6 O 1s high-resolution XPS spectrogram of MNNO prepared for Example 1.

[0131] Figure 7 Mn high-resolution XPS spectrogram of MNNO prepared for Example 1.

[0132] Figure 8 X-ray diffraction (XRD) diagram of the crystal structure of MNNO@MS prepared for Example 1.

[0133] Figure 9 SEM image of MNNO@MS prepared for Example 1.

[0134] Figure 10 HRTEM image of MNNO@MS prepared for Example 1.

[0135] Figure 11 Amplitude and phase images of PFM induced piezoelectric response in NNO, MNNO, MS, MNNO@MS prepared for Example 1.

[0136] Figure 12 Butterfly hysteresis loop of NNO prepared for Example 1.

[0137] Figure 13 Butterfly hysteresis loop of MNNO prepared for Example 1.

[0138] Figure 14 Butterfly hysteresis loop of MS prepared for Example 1.

[0139] Figure 15 Butterfly hysteresis loop of MNNO@MS prepared for Example 1.

[0140] Figure 16 Mo high resolution XPS spectra of surface chemical environment of MNNO@MS prepared for Example 1.

[0141] Figure 17 ALP cell staining of MNNO@MS prepared for Example 1 and Control.

[0142] Figure 18 ARS cell staining of MNNO@MS prepared for Example 1 and Control.

[0143] Figure 19 In vitro antibacterial performance of MNNO@MS prepared for Example 1

[0144] Figure 20 DCFH-HA fluorescent probe staining of intracellular ROS of MNNO@MS prepared for Example 1 and Control.

[0145] Figure 21 Calcium ion influx of MNNO@MS prepared for Example 1 and Control. DETAILED DESCRIPTION

[0146] The application will be further described in the following examples without limiting the application to the examples described. The experimental methods in the following examples, if not otherwise specified, are selected according to the conventional methods and conditions, or according to the commercial instructions.

[0147] Example 1

[0148] The embodiment provides a preparation method of a manganese-doped sodium niobate / molybdenum diselenide heterojunction, comprising the following steps:

[0149] Step one: preparation of manganese-doped sodium niobate

[0150] In 50ml (8mol / L) sodium hydroxide aqueous solution, Nb2O5 and Mn(NO3)3 are added according to different element mole ratios (Nb:Mn), (1g of niobium oxide, manganese nitrate (according to the mass required by Mn(NO3)3 calculated according to the mole ratio, the actual used manganese nitrate is a commercially available 50% aqueous solution of manganese nitrate, and the density is 1.54g / ml) 17.53μL (2%), 35.06μL (4%), 52.59μL (6%) according to different proportions), stir uniformly and pour into a hydrothermal kettle (normal pressure), put the hydrothermal kettle into an oven to react at 160℃ for 12h, the obtained product is washed with water and ethanol, centrifuged to take the precipitate, then ultrasonic is taken for 30min to take the supernatant, centrifuged to take the precipitate, dried to obtain manganese-doped sodium niobate powder, and the particle size is 150-300nm (230nm). The specific samples are shown in Table 1.

[0151] Table 1. Sample grouping of manganese-doped sodium niobate

[0152]

[0153] Step two: preparation of manganese-doped sodium niobate / molybdenum diselenide heterojunction

[0154] In a mixed aqueous solution (25mL) of Na2MoO4·2H2O (1.5mmol) and SeO2 (3mmol), 15mL of 50% hydrazine hydrate is added, and stirred for 12h. Then the manganese-doped sodium niobate (MNNO, 1.5 mmol, 0.01g) prepared in the above step one is added to the above solution. After stirring uniformly, the mixture is transferred to a polytetrafluoroethylene-lined autoclave (200℃, pressure 0-0.5MPa), and hydrothermally treated at 200℃ for 24h. After cooling to room temperature, the precipitate is washed with ethanol and deionized water for several times, and then vacuum dried at 60℃ overnight. Finally, the heterojunction is calcined at 500℃ for 2h under an argon atmosphere. To obtain the manganese-doped sodium niobate / molybdenum diselenide heterojunction (MNNO@MS). The particle size of the molybdenum diselenide ranges from 25nm to 75nm. At the same time, according to the above method, without adding MNNO, pure molybdenum diselenide (MS) is prepared as a control group.

[0155] Before use, the sample is polarized by corona polarization. The polarization steps are as follows: 0.2g of manganese-doped sodium niobate / molybdenum diselenide heterojunction or manganese-doped sodium niobate powder is pressed into a disc with a diameter of 1cm and placed in a corona polarization device. The corona polarization voltage is 3.5kV and the polarization time is 20min. After polarization, the disc is ground into powder (pressure 6MPa) to obtain the corona-polarized sample.

[0156] Example 1

[0157] The manganese-doped sodium niobate prepared in Example 1 of this invention was analyzed by ultrasonic transient current, electrochemical impedance spectroscopy, microstructure, structure, and oxygen vacancy content.

[0158] First, the ultrasonic transient currents of NNO, MNNO2, MNNO, and MNNO6 prepared in Example 1 were studied, and the results are shown in Table 2 below. With the increase of Mn ion doping concentration, the current density first increased and then decreased (NNO: 0.43 μA / cm). 2 MNNO2: 1.29 μA / cm 2 MNNO: 2.03 μA / cm 2 MNNO6: 0.67 μA / cm 2 The current density is highest when the Mn doping concentration reaches 4%.

[0159] Table 2

[0160]

[0161] The electrochemical impedance spectroscopy of NNO, MNNO2, MNNO, and MNNO6 prepared in Example 1 was studied, and the results are as follows: Figure 5 As shown. Compared to other samples, the semicircular arc of MNNO is much smaller, indicating that MNNO has a lower electron transfer resistance. These results indicate that ( Figure 5 As shown in Table 2, charge separation capability and carrier concentration are closely related to the Mn ion doping level. When the Mn ion doping content is 4%, MNNO exhibits the best electron-hole separation and migration capability, showing potential as an excellent acoustic sensor. Therefore, MNNO is preferred for the preparation of heterojunctions.

[0162] SEM and DLS images show that NNO ( Figure 1 ), MNNO2 ( Figure 2 ), MNNO ( Figure 3 All of them have a blocky structure, MNNO6 ( Figure 4In addition to the block structure, the presence of a filamentous structure was also found in the SEM image. The particle size of MNNO4 was reduced (200 nm) compared to that of NNO (about 260 nm), indicating that Mn doping can reduce the particle size by inhibiting the growth of crystal nuclei.

[0163] The surface chemical environment of MNNO prepared in Example 1 above was studied by X-ray photoelectron spectroscopy (XPS), and the specific results are shown in Figure 6 and Figure 7 .

[0164] In the O 1s high-resolution XPS spectrum ( Figure 6 ), O1, O2 and O3 correspond to lattice oxygen, oxygen defects and surface adsorbed oxygen, respectively. According to the formula Vo / O (%) = content of oxygen vacancies / (content of oxygen vacancies + content of lattice oxygen + content of adsorbed oxygen) x 100%, the content of oxygen vacancies in MNNO is 20.92%. It shows that manganese doping can create oxygen vacancies. In the Mn high-resolution XPS spectrum ( Figure 7 ), there are Mn ions with variable valence in MNNO. The multi-valence ion form of Mn can theoretically provide various potential enzyme activities.

[0165] Effect Example 2

[0166] The manganese-doped sodium niobate / molybdenum diselenide heterojunction prepared in Example 1 of the application was analyzed in terms of micro-morphology, element distribution, crystal structure, piezoelectric performance, sonodynamic performance, enzyme activity and ion release.

[0167] First, the crystal structure of MNNO@MS was studied by X-ray diffraction (XRD), and the specific results are shown in Figure 8 , the standard PDF card number of NaNbO3 is 73-0803 ( Figure 8 , the blue part), the standard PDF card of MoSe2 is 29-0914 ( Figure 8 , the black part), and the results show that the diffraction peaks of MNNO and SeMo2 are all present in the diffraction peaks of MNNO@MS.

[0168] The micro-morphology of MNNO@MS prepared in Example 1 above was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the results are shown in Figure 9 and Figure 10 .

[0169] From the SEM image ( Figure 9 ), molybdenum diselenide was in situ grown on the surface of MNNO, and the HRTEM image ( Figure 10) indicates the existence of heterojunction interface between MNNO and MoSe2, and the lattice spacing of 0.402 nm is observed on one side of the interface, which is attributed to the (110) plane of MNNO. Compared with pure sodium niobate (0.390 nm), the lattice spacing is expanded, which is due to the introduction of Mn 2+ (80 pm) has a larger ionic radius than Nb 5+ (70 pm) and the introduction of oxygen vacancies. These results show that Mn ion doping leads to the lattice expansion of MNNO, causing lattice distortion, resulting in the existence of non-centrosymmetric structure in MNNO, increasing the polarity, so as to exhibit stronger piezoelectricity. On the other side of the interface, the lattice spacing of 0.650 nm is observed, which is attributed to the (002) plane of MoSe2.

[0170] The piezoelectric properties of NNO, MNNO, MS, MNNO@MS prepared in Example 1 above were studied by PFM method, and the results are shown in Figure 11 .

[0171] The amplitude and phase images of the piezoelectric response caused by PFM in the a part, b part, c part, d part of Figure 11 , show that NNO, MNNO, MS, MNNO@MS all have piezoelectricity. In the range of bias voltage from-10 to +10 V, the butterfly loop and phase hysteresis curve (P-H curve) Figure 12 , Figure 13 , Figure 14 , Figure 15 ) show that when the direction of applied voltage changes, the phase hysteresis curve undergoes a phase inversion of about 180°, which confirms the piezoelectricity of NNO and BCNNO. From the butterfly loop Figure 12 , Figure 13 , Figure 14 , Figure 15 , it can be seen that compared with NNO, the amplitude change of MNNO is increased, indicating that doping significantly improves the piezoelectricity. Further, compared with MNNO and MS, the amplitude change of MNNO@MS is higher, indicating that MNNO@MS produces greater strain under the action of electric field, indicating that the piezoelectricity of MNNO@MS is better. Combined with the butterfly loop, according to the local d 33 formula:

[0172]

[0173] A and V are the maximum amplitude of the butterfly loop and the corresponding voltage value, respectively, and A0 and V0 are the amplitude value and voltage value at the intersection.

[0174] The d33 of NNO, MNNO, MS, MNNO@MS is 21.43 pm / V, 108.52 pm / V, 49.33 pm / V, 193.33 pm / V respectively, which shows that the heterojunction can enhance the polarization by forming the built-in stress at the heterojunction interface, and improve the piezoelectricity.

[0175] The surface chemical environment of MNNO@MS prepared in Example 1 is studied by XPS, and the specific results are shown in Figure 16 In the Mo high-resolution XPS spectrum, there are Mo ions with variable valence in MNNO@MS. The multi-valence ion form of Mo can theoretically provide various potential enzyme activities.

[0176] The sonodynamic performance of NNO, MNNO, MS, MNNO@MS prepared in Example 1 is further studied by detecting the degradation effect of rhodamine B, and the specific test conditions are as follows: the US (ultrasonic irradiation) parameters are 1 MHz, 1.5 W / cm 2 ; the concentration of RhB (solvent is water) is 10 mg / L. After US irradiation for 5 min, the supernatant is centrifuged, and the absorbance of the supernatant at 550 nm is measured by ultraviolet spectrophotometer. The detection results are shown in Table 3.

[0177] Among them, the Control group is a pure RhB solution; the rest of the groups are based on the RhB solution and add each group of samples with a concentration of 250 ug / mL (MNNO), 250 ug / mL (MS), 500 ug / mL (MNNO@MS).

[0178] The results show that MNNO@MS has the best sonodynamic performance. This is because the heterojunction enhances the macroscopic polarization electric field, so that its piezoelectric performance is improved, and under the trigger of US, the built-in electric field is generated, the piezoelectricity promotes the band bending, promotes the separation of electrons and holes, accelerates the charge transfer rate, and catalyzes the conversion of H2O and O2 in the surrounding environment into ROS (·OH and ·O2 - ), thereby enhancing the sonodynamic performance.

[0179] Table 3

[0180]

[0181] The heterojunction MNNO@MS prepared in Example 1 of the application is analyzed for POD-like enzyme activity. Specifically, 3,3',5,5'-tetramethylbenzidine (1.2 mM) is used as a substrate, and the POD simulation activity of the nanoparticles is measured in the presence of H2O2 (30 mM). 500 ug / mL of nanoparticles are dispersed in a TMB solution (pH=5.5) (solvent is deionized water), and the ultrasonic (1.5 W / cm 2After 10 minutes of reaction under ultrasound (1 MHz, 50% duty cycle) or without ultrasound, the supernatant was centrifuged and the absorption spectrum was determined using UV-vis-NIR. The results are shown in Table 4.

[0182] The Control group is a control group without nanoparticles. The other groups are based on the Control group, and each group of samples is added with a concentration of 250 ug / mL (MNNO), 250 ug / mL (MS), and 500 ug / mL (MNNO@MS).

[0183] Compared with NNO, MNNO, MS, and MNNO@MS all have POD-like enzyme activity. The piezoelectric response triggered by ultrasound can enhance the POD-like enzyme activity of MNNO@MS.

[0184] Table 4

[0185] POD (pH = 5.5):

[0186]

[0187] The CAT-like enzyme activity of NNO, MNNO, MS, and MNNO@MS prepared in Example 1 above was detected using a dissolved oxygen meter. Specifically, 50 mg of the sample was immersed in a 50 mL aqueous solution containing 10 mM H2O2, and the pH of the solution was adjusted using hydrochloric acid (0.1 mol). At different times (every 5 min within 1 h), the dissolved oxygen content (mg / L) was detected using a dissolved oxygen meter to verify the CAT-like enzyme activity. In addition, MNNO@MS was given US stimulation (1 MHz, 0.5 W / cm 2 ). The results are shown in Table 5.

[0188] The Control group is a control group without nanoparticles. The other groups are based on the Control group, and each group of samples is added with a concentration of 250 ug / mL (MNNO), 250 ug / mL (MS), and 500 ug / mL (MNNO@MS).

[0189] MNNO, MS, and MNNO@MS all have CAT-like enzyme activity. The piezoelectric response triggered by ultrasound can enhance the CAT-like enzyme activity of MNNO@MS. These results show that MNNO@MS can form a heterojunction, use the electron transfer at the heterojunction interface, and accelerate the generation and movement of electrons through the piezoelectric effect to improve the enzyme-like activity.

[0190] Table 5

[0191] CAT (pH = 7.4):

[0192]

[0193] Example 3

[0194] The antibacterial performance, oxidation resistance and osteoblast response of the manganese-doped sodium niobate / molybdenum diselenide heterojunction prepared in Example 1 of the present application were studied.

[0195] The in vitro antibacterial performance of MNNO@MS prepared in Example 1 of the present application was studied.

[0196] The bacteria were divided into 7 groups:

[0197] (1) Control group;

[0198] (2) H2O2 group;

[0199] (3) US group;

[0200] (4) MNNO@MS group;

[0201] (5) MNNO@MS+H2O2 group;

[0202] (6) MNNO@MS+US group;

[0203] (7) MNNO@MS+H2O2+US group.

[0204] The samples were co-cultured with S. aureus, and the antibacterial ratio was determined by colony counting method. The samples were sterilized by ultraviolet irradiation for 12 h. The bacterial suspension (1 mL) with a concentration of 1×10 6 CFU / mL was co-cultured with the samples (500 ug / mL) in a 24-well plate for 24 h: for the H2O2 group, 1 mM H2O2 was added to each group. For the US group, each group was ultrasonicated for 15 min (1.5 W / cm 2 , 1 MHz, 50% duty cycle). After 6 h of continuous co-culture, subsequent tests were performed. The cultured bacterial suspension was diluted 10-fold, and the bacterial suspension (20 μL) was spread on nutrient agar plates, which were incubated at 37°C for 24 h. Photographs were taken and colonies were counted. The antibacterial ratio calculation formula: Antibacterial ratio (%) = (C-S) / S, where C and S are the number of colonies in the Control group and the sample group, respectively. The test results are shown in Table 6 and Figure 19

[0205] Table 6

[0206]

[0207] ​Results show that compared with the Control group (3.50%), H2O2 (18.33%), US (24.71%) and MNNO@MS alone have only weak antibacterial ability. Under the action of H2O2, MNNO@MS+H2O2 has good antibacterial effect (83.48%), which is that the heterojunction improves the enzyme-like activity of MNNO@MS in the presence of bacteria in an acidic environment. In the presence of US, MNNO@MS+US also has good antibacterial ability (86.69%), because the piezoelectric effect enhances the sonodynamic effect. Further, the MNNO@MS+H2O2+US group obtains the best antibacterial effect (99.32%). This is because the piezoelectric effect of the heterojunction synergistically enhances the sonodynamic effect and the enzyme-like activity, and the combination of the two produces multiple ROS, which synergistically kills a large number of bacteria.

[0208] The cells used in this example are rat bone marrow mesenchymal stem cells (rBMSCs). The specific cell culture is as follows: rBMSCs are cultured in aMEM medium supplemented with 10% fetal bovine serum and 1% penicillin / streptomycin, the incubator is set to 37°C, 5% CO2 atmosphere, and the medium is replaced every 2 days. rBMSCs of 3-5 passages are used for cell experiments.

[0209] After the sample is sterilized by ultraviolet irradiation, it is divided into 5 groups:

[0210] (1) Control;

[0211] (2) H2O2;

[0212] (3) H2O2+US;

[0213] (4) MNNO@MS+H2O2;

[0214] (5) MNNO@MS+H2O2+US.

[0215] The US power is 1 MHz, 0.5 W / cm 2 , 20 seconds / time, 3 times / day. After the cells adhere, the cell culture medium is replaced with a medium containing 100 μM of H2O2. After 1 day and 3 days of culture with the sample, the culture medium is removed, and CCK-8 is used to detect the proliferation of cells on the sample. The specific results are shown in Table 7. The results show that after H2O2 treatment, compared with the Control group, the proliferation of cells is significantly inhibited (52.67%). MNNO@MS+H2O2 significantly promotes cell proliferation (89.67%) due to the enzyme-like activity. Under the stimulation of US, MNNO@MS+H2O2+US eliminates oxidative stress due to the piezoelectric effect and its amplified enzyme-like activity, further promoting cell proliferation (96.42%).

[0216] Table 7

[0217]

[0218] The ability of MNNO@MS to scavenge intracellular ROS was investigated. The specific experimental steps were consistent with the above. After co-culturing for 1 d, the culture medium was removed, and the samples were stained with DCFH-HA fluorescent probe for intracellular ROS. CLSM was used to observe the stained cells. The ROS fluorescence intensity was quantitatively analyzed by Image J software (Table 8, Figure 20 ). The results showed that after treatment with H2O2, the ROS level was significantly increased (21953.50 a.u.). MNNO@MS+H2O2could significantly reduce the ROS level in rBMSC cells (4192.70 a.u.), and under ultrasonic stimulation, the ROS level was further decreased (1257.11 a.u.).

[0219] Table 8

[0220]

[0221] The effect of MNNO@MS on the osteogenic differentiation of rBMSC was further studied. The samples were divided into 4 groups:

[0222] (1) H2O2;

[0223] (2) H2O2+US;

[0224] (3) MNNO@MS+H2O2;

[0225] (4) MNNO@MS+H2O2+US.

[0226] First, alkaline phosphatase (ALP) staining and ALP activity quantitative analysis were used to evaluate the early osteogenic differentiation of cells. After the cells were cultured with the samples for 14 d, the cells were fixed with 4% paraformaldehyde, the cells on the samples were stained using an alkaline phosphatase color reagent kit, and the staining of the 7th day was observed using an optical microscope. In order to quantitatively analyze the ALP activity, 1% Nonidet P-40 solution was added to the hole plate to lyse the cells for 1 h, and centrifuged (2000 rpm) for 10 min. After treatment with an alkaline phosphatase detection kit, the absorbance (OD value) of the solution was measured at 405 nm using a microplate reader. The total protein amount was determined using a BCA protein determination kit, and the ALP activity was calculated according to the absorbance at 405 nm divided by the total protein amount. The specific ALP staining diagram is shown in Figure 17 , and the ALP activity is shown in Table 9.

[0227] Table 9

[0228]

[0229] Secondly, Alizarin Red S (ARS) staining and calcium nodule quantification were used to evaluate the late osteogenic differentiation of cells. After 21 d of cell culture with samples, cells were fixed with 4% PA and stained with 1% ARS solution on the samples, and the staining of the 21st day was observed using an optical microscope. For ARS quantification, the samples were immersed in a 10% cetylpyridinium chloride solution for 1 h, and the absorbance of the solution was measured at 620 nm. The specific ARS staining diagram is shown in Figure 18 Table 10 shows the calcium nodule quantification.

[0230] Table 10

[0231]

[0232] According to Figure 17 , Figure 18 , Table 9, Table 10, it can be seen that: compared with the mineral deposition (H2O2: 1.75 IU / g; H2O2+US: 2.20 IU / g) and calcium nodule formation (H2O2: 0.118; H2O2+US: 0.139) of the H2O2 group and the H2O2+US group, the MNNO@MS+H2O2 group (6.72 IU / g, 0.621) was significantly enhanced, which indicated that the MNNO@MS combined ion release and oxidative stress relief synergistically promoted osteogenic differentiation. After further applying electric stimulation, the differentiation of osteogenic differentiation was more significant, and due to the piezoelectricity of MNNO@MS and its enhanced enzyme-like activity, it showed the best mineral deposition (7.42 IU / g) and calcium nodule (0.836) formation.

[0233] The possible mechanism of electric stimulation promoting osteogenic differentiation involves the up-regulation of intracellular Ca 2+ concentration related to osteoblasts, the main opening of voltage-gated Ca 2+ channels and the acceleration of osteogenesis through the up-regulation of calmodulin signaling pathways. Therefore, the intracellular Ca 2+ content was studied by Fluo-4 probe (Table 11 Figure 21 ).

[0234] Table 11

[0235]

[0236] The results show that after applying electrical stimulation, the MNNO@MS+H2O2+US group (11436.25 a.u.) exhibits stronger calcium signals than the MNNO@MS+H2O2 group (5876.29 a.u.), indicating that electrical stimulation significantly promotes calcium ion influx to promote osteogenic differentiation. These results show that MNNO@MS can positively affect the proliferation and differentiation of BMSC cells by eliminating oxidative stress, releasing bioactive factors, and opening calcium ion influx pathways through electrical stimulation.

[0237] Note: "US" means ultrasonic irradiation, and the irradiation conditions are (1 MHz, 0.5 W / cm 2 ) / / .

[0238] In summary, the present application prepared manganese-doped sodium niobate piezoelectric material with appropriate oxygen vacancies by hydrothermal method. Through appropriate oxygen vacancies and ion doping to increase polarization, improve piezoelectricity, and promote electron-hole separation. It is easier to be excited by US to produce sonodynamic effect, and can improve its POD and CAT enzyme activity. Then the correct manganese-doped sodium niobate / molybdenum diselenide heterojunction (MNNO@MS) is prepared by hydrothermal method. The heterojunction structure enhances the piezoelectric properties of MNNO@MS compared with MNNO and MS. Therefore, under the trigger of US, MNNO@MS can generate an internal electric field through enhanced piezoelectric effect, promote electron-hole separation and migration, improve charge transfer rate, and enhance sonodynamic effect. In addition, piezoelectric effect and heterojunction interface also promote the valence state transformation of Mn ions and Mo ions, which together improve the POD-like and CAT-like enzyme activity of MNNO@MS. Therefore, MNNO@MS heterojunction has enhanced piezoelectric properties, sonodynamic properties and enzyme-like activity. Antibacterial experiments show that under the infected microenvironment, MNNO@MS heterojunction generates a large amount of ROS due to enhanced sonodynamic effect and enzyme-like activity through piezoelectric response, which synergistically kills S. aureus. Under physiological conditions, MNNO@MS heterojunction relieves oxidative stress, promotes osteoblast response due to enzyme-like activity, piezoelectric response, and enhanced enzyme-like activity through piezoelectric response. The present application proposes a new strategy for piezoelectric effect and enhanced nanoscale enzyme activity and sonodynamic effect to synergistically promote osteoblast response and antibacterial effect. It can be used as an antibacterial bone repair material and has great application prospect in the field of bacterial infection and tissue healing.

[0239] The above merely describes preferred embodiments of the present application, and is not intended to limit the present application in any form or in essence. It should be noted that those skilled in the art can make some improvements and supplements without departing from the method of the present application, and these improvements and supplements should also be considered as the protection scope of the present application. For those skilled in the art, some slight changes, modifications and equivalent changes made by using the disclosed technical content without departing from the spirit and scope of the present application are equivalent embodiments of the present application; meanwhile, any equivalent changes, modifications and evolution made according to the essential technology of the present application to the above embodiments are still within the scope of the technical solutions of the present application.

Claims

1. A sodium niobate / molybdenum diselenide heterojunction, characterized in that, It includes manganese-doped sodium niobate and molybdenum diselenide, wherein the molar ratio of Nb to Mo ions in the manganese-doped sodium niobate and molybdenum diselenide is 1.5:(0.5~3).

2. The sodium niobate / molybdenum diselenide heterojunction as described in claim 1, characterized in that, It meets one or more of the following conditions: (1) The molar ratio of Nb to Mo ions in the manganese-doped sodium niobate and molybdenum diselenide is 1.5:(0.5~2); for example, 1.5:1.5; (2) In the manganese-doped sodium niobate, the molar ratio of manganese to niobium is x:(100-x); 0 < x < 6; for example, 1 < x < 5; preferably 2 < x < 4; more preferably x = 4; (3) The sodium niobate / molybdenum diselenide heterojunction is a composite structure of two semiconductors; Among them, manganese-doped sodium niobate is a wide bandgap semiconductor, with a preferred bandgap of 2.5~3.0 eV; Molybdenum diselenide is a narrow bandgap semiconductor, with a preferred bandgap of 1.2~1.7 eV; (4) The particle size of the molybdenum diselenide is 25~75nm; preferably 35~55nm; (5) The particle size of the manganese-doped sodium niobate is 100~350nm, preferably 170~230nm; (6) The particle size of the sodium niobate / molybdenum diselenide heterojunction is 200-450 nm, preferably 250-350 nm; (7) There is a heterojunction interface between the manganese-doped sodium niobate and molybdenum diselenide in the sodium niobate / molybdenum diselenide heterojunction; The lattice spacing on the manganese-doped sodium niobate side is preferably 0.35~0.5 nm, more preferably 0.39~0.41 nm; for example, 0.40 nm. The lattice spacing on one side of the molybdenum diselenide is preferably 0.55~0.7 nm; more preferably 0.64~0.66 nm. (8) The d of the sodium niobate / molybdenum diselenide heterojunction 33 Approximately 150~250 pm / V; for example, 180~200 pm / V; (9) The acoustic current density of the manganese-doped sodium niobate is 1.4~2.5 μA / cm. 2 For example, 2.00~2.20 μA / cm 2 .

3. A manganese-doped sodium niobate, characterized in that, In the manganese-doped sodium niobate, the molar ratio of manganese to niobium is x:(100-x); 0<x<6.

4. The manganese-doped sodium niobate as described in claim 3, characterized in that, It meets one or more of the following conditions: (1) The molar ratio of manganese to niobium is x:(100-x); 1<x<5; for example, 2<x<4; (2) The particle size of the manganese-doped sodium niobate is 100~350nm, preferably 170~230nm; (3) The manganese-doped sodium niobate is a wide bandgap semiconductor, preferably with a bandgap of 2.5~3.0 eV; (4) The acoustic current density of manganese-doped sodium niobate is 1.4~2.5 μA / cm. 2 For example, 2.00~2.20 μA / cm 2 .

5. A method for preparing manganese-doped sodium niobate, comprising the following steps: Sodium, manganese, and niobium sources are reacted to obtain the manganese-doped sodium niobate; wherein, the molar ratio of manganese to niobium in the sodium, manganese, and niobium sources is x:(100-x); 0<x<6.

6. The method for preparing manganese-doped sodium niobate as described in claim 5, characterized in that, It meets one or more of the following conditions: (1) The molar ratio of manganese to niobium is x:(100-x); 1<x<5; for example, 3<x<5; preferably x=4; (2) In sodium and niobium sources, the molar ratio of sodium to niobium is (10~60):1, for example (13~54):1; (3) The sodium source is sodium oxalate, sodium phosphate, sodium carbonate, sodium nitrate, sodium acetate, NaOH, NaOH solution, or NaCl; preferably NaOH solution; (4) The manganese source is Mn(NO3)3; (5) The niobium source is niobium alkoxide, Nb2O5 or potassium niobate; the niobium alkoxide is niobium pentaethoxy; (6) The preparation method is solid-phase reaction method, sol-gel method, hydrothermal synthesis method, molten salt method or coprecipitation method.

7. The method for preparing manganese-doped sodium niobate as described in claim 6, characterized in that, When the preparation method is a hydrothermal synthesis method, it includes the following steps: A mixture of sodium, manganese, and niobium sources is reacted under heating and pressure to obtain the manganese-doped sodium niobate. Preferably, it satisfies one or more of the following conditions: (1) The heating temperature is 120-200℃, preferably 160℃; (2) The pressurization pressure is 0.1~0.5MPa; preferably 0.1013MPa; (3) After the reaction is completed, the following post-processing steps are also included: After heating and pressurizing to carry out the reaction, the mixture is washed and sonicated, and the upper fine particle dispersion is taken; the fine particle dispersion is centrifuged to collect the precipitate, dried, and the manganese-doped sodium niobate is obtained. The washing process involves washing multiple times with deionized water and anhydrous ethanol. The ultrasound is preferably performed in water; The ultrasound duration is preferably 10-40 minutes, for example, 30 minutes; The preferred temperature for the ultrasound is room temperature. The preferred frequency of the ultrasound is 40 kHz; The centrifugation frequency is preferably 6000~9000 rpm, for example 8000 rpm; The centrifugation time is preferably 3 to 7 minutes, for example, 5 minutes; The drying temperature is 40-80℃, for example, 60℃; the drying pressure is atmospheric pressure. The drying process preferably further includes the following steps: The manganese-doped sodium niobate is pressed and corona-polarized; The pressing is preferably performed by pressing 0.2g of the manganese-doped sodium niobate into discs of 0.5-1.5cm in diameter; more preferably, discs of 1cm in diameter. The voltage for corona polarization is 3~5kV, for example 3.5kV; (4) The sodium source is a 1-10 mol / L NaOH aqueous solution.

8. A manganese-doped sodium niobate, prepared by the method according to any one of claims 6-7.

9. A method for preparing a sodium niobate / molybdenum diselenide heterojunction, comprising the following steps: Na₂MoO₄·2H₂O, SeO₂, and hydrazine hydrate are mixed and reacted with manganese-doped sodium niobate as described in any one of claims 1-2, then dried and calcined to obtain the sodium niobate / molybdenum diselenide heterojunction; wherein the molar ratio of Na₂MoO₄·2H₂O, SeO₂, and manganese-doped sodium niobate is 1.5:3:(0.5-3). Preferably, it satisfies one or more of the following conditions: (1) The molar ratio of Na2MoO4·2H2O, SeO2, hydrazine hydrate and manganese-doped sodium niobate is 1.5:3:(0.1-0.2):(0.5~2), preferably 1.5:3:(0.15):(0.5~2); for example, 1.5:3:(0.15):1.5; (2) The mixing time is 10-14 hours, for example, 12 hours; (3) The heating temperature is 120-250℃, preferably 200℃; (4) The heating is carried out in a stainless steel hydrothermal reactor lined with polytetrafluoroethylene; (5) The heating time is 8-30 hours, for example 24 hours; (6) The heating process also includes a washing step, wherein the washing is performed multiple times with deionized water and anhydrous ethanol; The washing and drying process takes place at a temperature of 40-80°C, for example, 60°C; the drying pressure is atmospheric pressure. (7) The calcination is carried out under an argon atmosphere; (8) The calcination temperature is 400℃-600℃, for example 500℃; (9) The calcination time is 1-3 hours, for example, 2 hours; (10) The calcination is carried out in an argon atmosphere at a temperature of 500°C for 2 hours.

10. A sodium niobate / molybdenum diselenide heterojunction, prepared by any one of the preparation methods in claims 7-8; preferably, it is as described in claim 1 or 2.

11. Use of a manganese-doped sodium niobate or a sodium niobate / molybdenum diselenide heterostructure in the preparation of bone repair materials; wherein the manganese-doped sodium niobate is as described in claim 3 or 4, and the sodium niobate / molybdenum diselenide heterostructure is as described in claim 1 or 2.

12. The use of a manganese-doped sodium niobate or a sodium niobate / molybdenum diselenide heterostructure as a bone repair material; wherein the manganese-doped sodium niobate is as described in claim 3 or 4, and the sodium niobate / molybdenum diselenide heterostructure is as described in claim 1 or 2.

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