A biomimetic scaffold material for promoting repair and reconstruction of infectious bone defects and a preparation method and application thereof

Abstract

The present application relates to the technical field of biomimetic medical materials, in particular to a kind of biomimetic scaffold material for promoting the repair and reconstruction of infected bone defect and its preparation method and application.The preparation method is, by temperature control, oxygen vacancy titanium dioxide nanorod is wrapped in collagen inside, and makes mineralized crystal directional deposition in collagen internal gap area, obtains the porous biomimetic scaffold with bone-like structure.The biomimetic scaffold material of the present application has bone-like structure, not only can realize efficient physical antibiosis after ultrasonic irradiation, but also can adjust the cytophagous action of macrophage to promote tissue repair, and the repair and reconstruction effect of the material for infected bone defect has been verified in animal experiment.The successful preparation of the present application material can realize the precise antibiosis of space-time controllable, and further promote the repair and regeneration of bone tissue, provide a new method for the clinical treatment of bone defect, especially the bone defect related diseases with infection.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomimetic medical materials, in particular to a biomimetic scaffold material for promoting repair and reconstruction of infected bone defects and a preparation method and application thereof. BACKGROUND

[0002] In recent years, the incidence of bone defect-related diseases caused by factors such as trauma, tumor, congenital malformation, etc. is increasing year by year. Due to many factors such as wound opening, tissue diffusion, surgical exposure, etc., the defect area is often invaded by bacteria, causing more complex infected bone defects. The presence of infection can seriously damage the regenerative capacity of local tissues and bones, making the defect difficult to heal, which greatly hinders the treatment and repair of bone defects. Therefore, the treatment of infected bone defects has become a bottleneck problem that needs to be solved in clinical practice.

[0003] The treatment of infected bone defects includes two tasks of infection control and bone defect repair and reconstruction. For bone infection control, the current more reliable treatment is surgical debridement combined with antibiotic therapy. However, antibiotics have disadvantages such as narrow antibacterial spectrum, destruction of the body's microbial and immune environment, and easy drug resistance due to long-term and large-scale use. Bacteria can avoid the attack of antibiotics through mechanisms such as secretion of inactivating enzymes, drug efflux pumps, targeted modification and penetration barrier. In comparison, physical antibiosis rarely produces drug resistance. Among them, sonodynamic therapy can produce a large number of active oxygen through the interaction of ultrasound and sonosensitizers, directly destroy the integrity of the cell membrane of pathogenic bacteria to induce bacterial death. Compared with traditional antibiotic therapy, sonodynamic therapy not only has good broad-spectrum antibacterial properties, but also has small tissue damage and strong tissue penetration ability, and has good clinical application prospects in the treatment of infectious diseases.

[0004] For bone defect reconstruction, bone transplantation is usually used. Autologous bone transplantation is the gold standard for clinical treatment, but it has problems such as insufficient donor bone volume and complications in the donor area; and allogeneic transplantation is also limited by potential immune rejection and infection risk. Therefore, the clinical application of natural bone transplantation has great limitations. In recent years, many bone replacement materials have appeared, which can promote bone repair by simulating the composition and physicochemical properties of natural bone. However, the existing bone repair materials usually do not have self-antibacterial properties and have poor immune microenvironment regulation ability in the damaged local area, and have limited treatment ability for more complex infected bone defects. The phagocytosis of macrophages can remove apoptotic cells and cell fragments, prevent the continuous release of harmful substances, and maintain immune homeostasis. Studies have shown that restoring the phagocytosis of damaged macrophages can promote the regeneration and repair process of the defect tissue. SUMMARY

[0005] Based on the limitations of the traditional clinical treatment method and the current research status of the defect repair field, the purpose of the present application is to provide a kind of biomimetic scaffold material and its preparation method and application, which can realize high-efficiency antibiosis under ultrasonic irradiation and promote the repair and reconstruction of infectious bone defects by adjusting the phagocytosis of macrophages.

[0006] To solve the above technical problems, the present application provides the following technical solutions:

[0007] A preparation method of a biomimetic scaffold material for promoting the repair and reconstruction of infectious bone defects, specifically: by temperature control, oxygen vacancy titanium dioxide nanorods are wrapped in collagen, and mineralized crystals are deposited in the interstitial region of collagen, obtaining a porous biomimetic scaffold with bone-like structure. While improving the mechanical properties and bone conduction properties of the scaffold material, it also has multi-dimensional and multi-functional characteristics to better match the clinical treatment needs.

[0008] Among them, the preparation method of the oxygen vacancy titanium dioxide nanorod (TiO 2-x ) is to use titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation to obtain oxygen vacancy titanium dioxide nanorods.

[0009] Among them, the titanium precursor solution is to dissolve titanium tetrachloride and oleic acid in 1-octadecene to prepare a titanium precursor solution containing 0.2 M titanium tetrachloride and 1.0 M titanium tetrachloride.

[0010] Among them, in the preparation method of the oxygen vacancy titanium dioxide nanorod, 1-octadecene, oleylamine and oleic acid are added to the reactor and heated under vacuum at 90℃, then cooled to 60℃ under N2; then the titanium precursor solution is injected into the system, then rapidly heated to 290℃ and kept at this temperature for a period of time, the remaining titanium precursor solution is added at a certain rate, after cooling to room temperature, collect the titanium dioxide nanorods, wash with isopropanol, and centrifuge at 8000 rpm to obtain oxygen vacancy titanium dioxide nanorods.

[0011] Further, the type I mouse tail collagen solution is concentrated to 8-10 mg / mL, the prepared oxygen vacancy titanium dioxide nanorods are mixed with the type I mouse tail collagen solution, and the mixture is stirred under constant temperature and light protection; then the mixed solution is slowly injected into the dialysis bag, and the dialysis bag is transferred to a mineralization solution that can provide calcium, phosphorus and other mineralization related substances, and assembled in a constant temperature shaker for 7-10 days, and the fresh mineralization solution is replaced every other day, then after the steps of freeze-drying, cross-linking and washing, the three-dimensional porous biomimetic scaffold material is obtained.

[0012] The preparation method of the mineralized solution is as follows: 8g of NaCl, 3g of Na2HPO4, 0.2g of KCl and 0.35g of KH2PO4 are weighed and dissolved in 1L of deionized water for standby use; before each use, 100mL of the above solution is taken, 47.9mg of K2HPO4, 66.2mg of CaCl2·2H2O and 10mg of polyaspartic acid are added, and the solution is fully dissolved.

[0013] Pre-freezing at-20℃ for 24h before freeze-drying, freeze-drying time is 12-14h; the crosslinking agent used is 80% anhydrous ethanol solution containing 1-ethyl (3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC), and the crosslinking time is 4-5 hours.

[0014] The light-proof constant temperature stirring temperature is 25±0.5℃; and the temperature of the constant temperature shaker is 37±0.5℃.

[0015] The present application controls the temperature to make the oxygen vacancy titanium dioxide nanorod and the mineralized crystal directional assembly in the collagen fiber, forms the biomimetic scaffold material with the ultrasonic response performance, the macrophage regulation performance and the similar structure and component of the natural bone under the premise of not changing the original topological structure and physical and chemical properties of the collagen. The biomimetic scaffold material prepared by the present application can produce active oxygen through the sonodynamic effect under ultrasonic irradiation, and has high efficient physical antibacterial effect. The antibacterial rate can reach more than 95% by using ultrasonic (1MHz, 50% air occupancy, 1.5 W / cm 2 ) irradiation for 15 minutes. The phagocytosis of macrophages can also be adjusted, and the tissue repair is further promoted.

[0016] The biomimetic scaffold material has good biocompatibility, can produce a large amount of active oxygen under the action of ultrasound to achieve high efficient physical antibacterial effect and reduce the occurrence of infection; in addition, the scaffold material can adjust the phagocytosis of macrophages, play the role of bone guidance, reshape the local immune microenvironment, and promote the repair and reconstruction of bone defects. The efficacy is preliminarily verified in an infected bone defect animal model. The material is implanted in the defect and combined with ultrasonic treatment, and excellent anti-infection and bone defect repair effect can be obtained.

[0017] Compared with the prior art, the biomimetic scaffold material for promoting repair and reconstruction of infected bone defects, the preparation method and application of the biomimetic scaffold material have at least the following beneficial effects:

[0018] (1) The biomimetic scaffold material prepared by the method has sonodynamic effect under ultrasonic irradiation, and plays a high-efficiency physical antibacterial performance; by temperature control, the oxygen vacancy titanium dioxide nanorod is assembled into the inside of the collagen fiber, the topological structure and physical and chemical properties of the collagen are not changed, and the antibacterial and anti-infection effects of the material are enhanced. Meanwhile, the material degrades slowly, can maintain the space structure of the bone defect area, and can adjust the cell corpse effect of macrophages, which is beneficial to the repair and reconstruction of bone defects. The material has important clinical significance for the precise treatment of bone defect related diseases, especially complex bone defects with infection.

[0019] (2) The treatment effect of the biomimetic scaffold material has been preliminarily verified in an animal model of infectious bone defects. The material is implanted in the defect and combined with ultrasonic treatment, and excellent anti-infection and bone defect repair effect can be obtained.

[0020] (3) The successful preparation of the material can be used for the treatment of refractory infectious bone defects in clinic, realizes the precise antibiosis of space-time controllable, and further promotes the repair and regeneration of bone tissue, thereby providing a new method for the clinical treatment of bone defects, especially bone defect related diseases with infection. The material has the dual advantages of infection control and defect reconstruction, can provide more choices for the clinical treatment of infectious bone defects, reduce the overall treatment cost of patients, alleviate the pain and treatment side effects of patients, and promote the development of biological medicine.

[0021] The biomimetic scaffold material for promoting repair and reconstruction of infectious bone defects, the preparation method and application thereof will be further described below in combination with the drawings. DESCRIPTION OF DRAWINGS

[0022] Figure 1 is the solution absorption spectrum of the mixture of oxygen vacancy titanium dioxide nanorods and 1,3-diphenyl isobenzofuran solution (DPBF) in Example 1 at different time points under ultrasonic irradiation, and the sonodynamic performance of the reaction material.

[0023] Figures 2-3 is the morphology and energy spectrum under a transmission electron microscope and the morphology under a scanning electron microscope of the oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material in Example 1. Among them, Figure 2 the left drawing in is a transmission electron microscope graph, and the right drawing is an energy spectrum thereof, Figure 3 is a scanning electron microscope graph.

[0024] Figure 4 is the cell proliferation of bone marrow mesenchymal stem cells co-cultured with the biomimetic mineralized scaffold material containing different concentrations of oxygen vacancy titanium dioxide nanorods for 1 day, 3 days and 5 days in Example 2.

[0025] Figure 5is the survival of bacteria after the oxygen vacancy titanium dioxide-biomimetic mineralization scaffold material was co-cultured with Staphylococcus aureus or Escherichia coli in Example 3, and was irradiated with 1 MHz, 50% empty occupation, 1.5 W / cm 2 for 15 minutes.

[0026] Figures 6-7 is the flow cytometry analysis result of detecting the strength of cell thanatosis after the oxygen vacancy titanium dioxide-biomimetic mineralization scaffold material was co-cultured with Raw264.7 cells for 24 hours in Example 4.

[0027] Figures 8-9 is the HE staining and Gram staining of the local defect area of the rats after the oxygen vacancy titanium dioxide-biomimetic mineralization scaffold material was used to treat the infected skull defect of the rats in Example 5, and 2 weeks after the operation. Among them, Figure 7 is the HE staining of each group, and the arrow shows the infiltration of inflammatory cells. Figure 8 is the Gram staining, and the arrow shows the distribution of gram-positive Staphylococcus aureus.

[0028] Figure 10 is the bone defect repair situation (left figure) and the new bone volume and BV / TV value (right figure) of each group in the defect area displayed by Micro-CT after 8 weeks and 12 weeks after the operation in Example 5, using the oxygen vacancy titanium dioxide-biomimetic mineralization scaffold material combined with ultrasound to treat the infected skull defect of the rats. DETAILED DESCRIPTION

[0029] Example 1 Preparation and morphology characterization of oxygen vacancy titanium dioxide-biomimetic mineralization scaffold material

[0030] (1) Synthesis of oxygen vacancy titanium dioxide nanorods (TiO 2-x ): Dissolve titanium tetrachloride (2.19 mL) and oleic acid (31.59 mL) in 1-octadecene (66.25 mL) to prepare a titanium precursor solution containing 0.2 M titanium tetrachloride and 1.0 M titanium tetrachloride, and store it in a glove box filled with N2. In a four-necked reactor, 1-octadecene (10 mL), oleylamine (10 mL), and oleic acid (0.48 mL) were heated at 90°C under vacuum for 1 hour to remove dissolved water and oxygen, and then cooled to 60°C under N2. Inject 1.5 mL of titanium precursor solution into the system, then quickly heat to 290°C and maintain at this temperature for 10 min. Add 8 mL of additional titanium precursor solution at a rate of 0.3 mL•min-1. After cooling to room temperature, collect the oxygen vacancy titanium dioxide nanorods, wash with isopropanol, and centrifuge at 8000 revolutions per minute for 8 min.

[0031] (2) Ultrasonic response performance detection of oxygen vacancy titanium dioxide nanorods: 1,3-diphenyl isobenzofuran solution (DPBF) was mixed with oxygen vacancy titanium dioxide nanorod suspension (final concentration 0.5 mg / mL), and the mixture was irradiated with ultrasound (1 MHz, 50% air occupancy, 1.5 W / cm 2 ) for 10 minutes. The absorption spectrum of the solution was recorded every 2 minutes and the corresponding curve was plotted. Figure 1 The results showed that the characteristic absorption peak of the solution at 410-420 nm gradually increased with time, indicating that the prepared oxygen vacancy titanium dioxide nanorods could produce reactive oxygen under the action of ultrasound, and the reactive oxygen production was positively correlated with the irradiation time.

[0032] (3) Preparation of oxygen vacancy titanium dioxide-bionic mineralized scaffold material (IMC / TiO 2-x ): Type I mouse tail collagen solution was concentrated to a concentration of 8-10 mg / mL, and the prepared titanium dioxide nanorods were mixed with the type I mouse tail collagen solution. The mixture was stirred in the dark at a constant temperature of 25±0.5℃ for 30 minutes. Then the mixture was slowly injected into a dialysis bag, and the dialysis bag was transferred to a mineralization solution that could provide mineralization-related substances such as calcium and phosphorus. The dialysis bag was assembled in a constant temperature shaker for 7-10 days, with the temperature set at 37±0.5℃, and the fresh mineralization solution was replaced every other day. The suspension obtained in the dialysis bag was gently taken out and poured into a mold. After pre-freezing at -20℃ for 24 h, freeze-drying was performed for 12-14 h. The material was taken out of the mold and cross-linked with 1-ethyl (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in 80% anhydrous ethanol solution for 4-5 hours to obtain the oxygen vacancy titanium dioxide-bionic mineralized scaffold material. The cross-linked scaffold material was washed with 1% glycine solution and deionized water alternately.

[0033] The specific configuration method of the mineralization solution is as follows: weigh 8 g of NaCl, 3 g of Na2HPO4, 0.2 g of KCl, and 0.35 g of KH2PO4, and dissolve them in 1 L of deionized water for standby use; before each use, take 100 mL of the above solution, add 47.9 mg of K2HPO4, 66.2 mg of CaCl2•2H2O, and 10 mg of polyaspartic acid, and dissolve thoroughly.

[0034] (4) Transmission electron microscope observation Figure 2 : Oxygen vacancy titanium dioxide and type I collagen were co-assembled for 48 h in the above manner. The formed composite material was placed on a nickel mesh, and 1-2% sodium phosphotungstate staining solution was used for negative staining, and the material was washed thoroughly with deionized water. After drying, the material morphology was observed by transmission electron microscope, and EDS energy spectrum analysis was performed to understand the distribution of C, N, O, Ti, Ca, and P in the material.

[0035] (5) Scanning electron microscope observationFigure 3 ): Take the prepared oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material in an appropriate amount, and perform gold spraying treatment. The surface morphology of the material is observed by scanning electron microscope.

[0036] Example 2: Determination of biocompatibility of oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material

[0037] (1) According to the preparation method of steps (1)-(3) in Example 1, mineralized collagen (IMC) and biomimetic mineralized scaffold material containing different concentrations of oxygen vacancy titanium dioxide (IMC / TiO 2-x ) (0.1 mg / mL, 0.25 mg / mL, 0.5 mg / mL, 1 mg / mL, 1.5 mg / mL, 2 mg / mL) were prepared for subsequent cell experiments.

[0038] (2) Co-culture of bone marrow mesenchymal stem cells (BMSCs) with the material: Bone marrow mesenchymal stem cells were subcultured in α-MEM medium containing 15% fetal bovine serum, and then seeded in a 48-well plate at a cell density of 6×10 3 cells / well. After the cells adhered, different scaffold materials prepared in step (1) were placed in the culture for 1 day, 3 days, and 5 days, and then the medium containing 10% CCK-8 was replaced, incubated at 37°C for 90 minutes, and the absorbance value of the solution at 450 nm was detected using a spectrophotometer (OD Figure 4 ). The results showed that when the assembly concentration of titanium dioxide nanorods reached 1.5 mg / mL, the material had no significant effect on cell survival rate, indicating that the oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material (IMC / TiO 2-x ) had good biocompatibility.

[0039] Example 3: Detection of antibacterial performance of oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material

[0040] (1) According to the preparation method of steps (1)-(3) in Example 1, mineralized collagen (IMC) and oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material (IMC / TiO 2-x ) were synthesized.

[0041] (2) The Staphylococcus aureus or Escherichia coli liquid in the logarithmic growth phase (OD 600 =1.0-1.5) was diluted to 1×10 7 CFU / mL and added to EP tubes containing mineralized collagen or oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material, and the light was balanced for 30 minutes. After that, the experimental group used ultrasonic waves (1 MHz, 50% air occupancy, 1.5 W / cm 2) for 15 min. The bacteria treated with different methods were diluted to proper concentration, and 50 μL of each was spread on LB agar plates using a spiral plater and incubated at 37 °C for 24 h. The results of colony counting showed that (Fig. 1) the number of colonies of bacteria treated with the oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material combined with ultrasonic treatment was significantly reduced, and the antibacterial rate was more than 95%. Figure 5

[0042] Example 4: Investigation of the ability of the oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material to regulate the phagocytosis of macrophages

[0043] (1) According to the preparation method of steps (1)-(3) in Example 1, mineralized collagen (IMC) and oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material (IMC / TiO 2-x ).

[0044] (2) Co-culture of Raw264.7 and materials: Raw264.7 cells were subcultured in DMEM high glucose medium (containing 10% fetal bovine serum), and then seeded in a 12-well plate at a cell density of 5×10 5 cells per well. After the cells adhered, the biomimetic scaffold material prepared in step (1) was placed (or not placed) and co-cultured for 24 h.

[0045] (3) Flow cytometry detection of phagocytosis: 1 μM of STS was added to the jurkat cell suspension to induce jurkat cell apoptosis. After 4 h, the cells were centrifuged, and the apoptotic jurkat cells were stained according to the PKH26 staining kit instructions. The apoptotic cells were added to the well plate with seeded Raw264.7 cells at a ratio of 5:1, and after 45 min, the Raw264.7 cells were washed with PBS three times, the cells were blown off, and FITC-F4 / 80 staining was performed. Flow cytometry was used to analyze the phagocytosis ratio of macrophages (i.e. the ratio of PKH26+FITC+ cells). The results showed that (Fig. 3) the double positive cell ratio of Raw264.7 cells co-cultured with the oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material increased significantly, indicating that the biomimetic scaffold material can enhance the phagocytosis of macrophages. Figures 6-7

[0046] Example 5: Therapeutic effect of the oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material on infected skull defects in rats

[0047] (1) According to the preparation method of steps (1)-(3) in Example 1, mineralized collagen (IMC) and oxygen vacancy titanium dioxide-biomimetic mineralized scaffold material (IMC / TiO 2-x ).

[0048] ​​(2) Establishment of a rat model of infectious skull defects: 6-8 week old SD rats were randomly divided into control group, IMC+US group, and IMC / TiO group. 2-x Group and IMC / TiO 2-x +US group. A rat model of infectious skull defect was established under general anesthesia: the skull was exposed by full-thickness incision, and a 5mm diameter circular defect was created bilaterally along the midline using an implantation machine. 100μL of Staphylococcus aureus bacterial suspension in the logarithmic growth phase was then applied (10... 7 (CFU / mL), after filling with the appropriate material, suture in layers for alignment. For the IMC+US group and IMC / TiO2 group... 2-x The +US group received ultrasound irradiation treatment on local tissues 1 and 3 days after surgery.

[0049] (3) Evaluation of anti-infective and osteogenic effects in the treatment of infected bone defects: Some rats were sacrificed after 2 weeks for HE (hematoxylin and eosin) treatment. Figure 8 ) and Gram staining ( Figure 9 The results showed that IMC / TiO 2-x The +US group showed the least amount of inflammatory cell infiltration and residual bacteria at the defect site, indicating that the oxygen-vacancy titanium dioxide-biomimetic mineralized scaffold material combined with ultrasound therapy has excellent anti-infective properties. Rats were sacrificed at 8 and 12 weeks for Micro-CT (micro-CT scan). Figure 10 The bone formation rate and BV / TV values ​​of each group were measured and analyzed. Results showed IMC / TiO₂ 2-x The +US group showed the highest amount of new bone formation at the defect site, demonstrating excellent bone defect repair. In conclusion, this oxygen-vacancy titanium dioxide-biomimetic mineralized scaffold material exhibits excellent therapeutic effects on infected bone defects.

[0050] The results of Examples 1-5 show that the oxygen-vacancy titanium dioxide-biomimetic mineralization scaffold material proposed in this invention can generate a large amount of reactive oxygen species under ultrasonic conditions to achieve highly efficient physical antibacterial activity. This biomimetic scaffold material exhibits good biocompatibility and osteoconductivity, and can regulate the burial of macrophages, promoting the regeneration and repair of damaged tissues by reshaping the local immune microenvironment. In an animal model of infectious bone defects, the use of this biomimetic scaffold material combined with ultrasound therapy achieved excellent anti-infection and defect repair effects. Therefore, the oxygen-vacancy titanium dioxide-biomimetic mineralization scaffold material proposed in this invention has significant advantages in addressing refractory infectious bone defects.

[0051] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing a biomimetic scaffold material to promote repair and reconstruction of an infected bone defect, characterized in that: By temperature control, the oxygen vacancy titanium dioxide nanorods are wrapped in the collagen, and the mineralized crystals are deposited in the gap region of the collagen, so that a porous biomimetic scaffold with a bone-like structure is obtained; The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained. In the preparation method of the oxygen vacancy titanium dioxide nanorods, 1-octadecene, oleylamine and oleic acid are added into a reactor, and then heated under vacuum at 90℃, and then cooled to 60℃ under N2; then the titanium precursor solution is injected into the system, and then rapidly heated to 290℃, and kept at this temperature for a period of time, and the remaining titanium precursor solution is added at a certain rate, and after cooling to room temperature, the titanium dioxide nanorods are collected, washed with isopropyl alcohol, and centrifuged at 8000 rpm to obtain the oxygen vacancy titanium dioxide nanorods.

2. The method of claim 1, wherein: The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained.

3. The method for preparing the biomimetic scaffold material according to claim 2, characterized in that: The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained.

4. The method of claim 1, wherein: The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained.

5. The method of claim 1, wherein: The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained.

6. The method of claim 1, wherein: The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained. The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained. The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained. The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained. The preparation method of the oxygen vacancy titanium dioxide nanorods comprises the following steps: taking titanium tetrachloride and oleic acid as raw materials to prepare a titanium precursor solution, then vacuum heating, cooling, rapid heating, washing and centrifugation are carried out, and finally the oxygen vacancy titanium dioxide nanorods are obtained.

7. The biomimetic scaffold material prepared by the preparation method of any one of claims 1-6.

8. The application of the biomimetic scaffold material of claim 7 in the preparation of anti-infection and bone defect repair materials.

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