A dual drug release system on titanium-based implant surface and its preparation method and application

Abstract

The present invention belongs to the technical field of medical materials, and relates to a dual-drug release system on the surface of a titanium-based implant, its preparation method and application. It includes a titanium-based implant and a hydrogel layer attached to its surface. The surface of the titanium-based implant is a nanotube array structure. Zinc oxide nanoparticles and upconversion luminescent material particles are provided between the titanium-based implant and the hydrogel layer, and MgO2 nanoparticles are loaded in the hydrogel layer; wherein, the material of the upconversion luminescent material particles is NaYF4:Yb 3+ ,Er 3+ , and the hydrogel layer is composed of a gelatin-sodium alginate hydrogel. The dual-drug release system on the surface of the titanium-based implant provided by the present invention can not only achieve the loading of different drugs and can be used to treat various diseases, but also has a good timing control effect, a long action time, a low cost, and has broad application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of medical materials and relates to a dual drug release system on the surface of a titanium-based implant and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Osteosarcoma is a common primary malignant tumor in children and adolescents. The current treatment method mainly involves surgical resection, followed by chemotherapy and radiotherapy to remove the surrounding residual tumor cells and tissues. However, this treatment method has obvious defects. Chemotherapy and radiotherapy can damage the surrounding normal tissues and cells, and the surrounding tumor tissues and cells that have not been removed may even have the risk of recurrence. At the same time, the filling site is prone to bacterial infection. At the same time, there are differences between individual patients, making it difficult to mass produce titanium implants. Among the many implant materials, 3D printed titanium and its alloys have been widely used in the treatment of bone tissue defects due to their good comprehensive properties. However, the surface of 3D printed titanium implants has limited ability to bond with the surrounding bone tissue, and has limited anti-tumor and anti-infection capabilities. Summary of the invention

[0004] In order to address the deficiencies in the prior art, the purpose of the present invention is to provide a titanium-based implant surface dual drug release system and a preparation method and application thereof. The titanium-based implant surface dual drug release system provided by the present invention can not only realize the loading of different drugs and can be used to treat a variety of diseases, but also has good timing control effect, long action time, low cost, and broad application prospects.

[0005] In order to achieve the above object, the technical solution of the present invention is:

[0006] In the first aspect, a dual drug release system on the surface of a titanium-based implant comprises a titanium-based implant and a hydrogel layer attached to the surface thereof, wherein the surface of the titanium-based implant is a nanotube array structure, zinc oxide nanoparticles and upconversion luminescent material particles are arranged between the titanium-based implant and the hydrogel layer, and MgO is loaded in the hydrogel layer. 2 Nanoparticles; wherein the material of the upconversion luminescent material particles is NaYF 4 : Yb 3+ , Er 3+ , the hydrogel layer is composed of gelatin-sodium alginate hydrogel.

[0007] First, micro-nano structures and zinc ions have been proven to have osteogenic and antibacterial effects. Therefore, the present invention first forms a nanotube array structure on the surface of the titanium-based implant and loads zinc oxide nanoparticles to make it have osteogenic and antibacterial effects. Secondly, magnesium peroxide has multiple effects of osteogenic, antibacterial and anti-tumor. Therefore, the present invention adds magnesium peroxide to the system. However, compared with metal oxides, magnesium peroxide has active chemical properties and is difficult to directly attach to the surface of the titanium-based implant. Therefore, the present invention adopts a hydrogel loading method and sets it on the titanium-based implant through a hydrogel layer. At the same time, the present invention sets upconversion luminescent material particles, which accelerate the degradation of the hydrogel system through its photothermal conversion ability, thereby achieving the release of magnesium peroxide and the delayed release of zinc oxide nanoparticles. The present invention selects NaYF 4 : Yb 3+ , Er 3+ It has good biocompatibility, thus maintaining the normal function of titanium-based implants; at the same time, NaYF 4 : Yb 3+ , Er 3+ The combination with gelatin-sodium alginate hydrogel is also beneficial to the release of dual drugs.

[0008] In a second aspect, a method for preparing the above-mentioned titanium-based implant surface dual drug release system comprises the following steps:

[0009] Preparation of MgO 2 Nanoparticles, and MgO 2 Nanoparticles are loaded into the hydrogel;

[0010] The residual particles on the surface of the titanium-based implant are removed by acid etching and anodizing, and a nanotube array is constructed on the surface to obtain a pretreated titanium-based implant; the solution used in the anodizing method contains fluoride ions;

[0011] First, zinc oxide nanoparticles are deposited on the surface of a pretreated titanium-based implant, and then upconversion luminescent material particles are deposited on the surface of the pretreated titanium-based implant by a hydrothermal method to obtain a titanium-based implant with a double surface modification;

[0012] Loading MgO 2 The hydrogel of nanoparticles is coated on the surface of titanium-based implant to obtain the implant.

[0013] The present invention first deposits zinc oxide nanoparticles on the surface of the pretreated titanium-based implant, which is beneficial to the subsequent NaYF 4 : Yb 3 + , Er 3+ Deposited on the surface of pretreated titanium-based implants; at the same time, since the preparation process of zinc oxide nanoparticles requires pyrolysis, this method avoids the need to deposit NaYF 4 : Yb3+ , Er 3+ NaYF induced by post-deposition ZnO nanoparticles 4 : Yb 3+ , Er 3+ Inactivation.

[0014] Anodic oxidation is a process in which titanium is used as an anode in a fluoride-based electrolyte and a constant voltage is applied to generate titanium dioxide nanotubes on the surface. During the anodization process, titanium reacts with the electrolyte under the action of an electric field to generate a titanium dioxide layer, but this will hinder the electrochemical reaction. At this time, titanium dioxide reacts with the fluoride in the solution. - The reaction generates water-soluble [TiF 6 ] 2- , exposing the titanium substrate, and a tightly packed array of nanotubes is formed in a dynamic cycle of dissolution and generation. As time goes by, the nanotubes gradually extend toward the substrate, thereby increasing in length. The reaction equation is as follows:

[0015]

[0016] In a third aspect, a dual drug release system on the surface of a titanium-based implant is used in the preparation of implant materials for treating osteosarcoma.

[0017] The beneficial effects of the present invention are:

[0018] The titanium-based implant surface dual drug release system provided by the present invention can realize the release of dual drugs under the excitation of near-infrared light (wavelength of 808nm) through the cooperation of upconversion luminescent materials and hydrogels, has good timing control effect and long action time.

[0019] In the preparation method provided by the present invention, a nanotube array is first constructed on the surface of a titanium-based implant and zinc oxide nanoparticles are attached to construct a first heavy zinc ion release system; then, through hydrothermal treatment, upconversion luminescent material particles are further deposited on the surface of the titanium-based implant to construct a photothermal switch; then, MgO is loaded through a gelatin-sodium alginate system. 2 Nanoparticles are coated on titanium-based implants to construct a second drug release system. Under the irradiation of near-infrared light, the surface temperature rises, accelerating the degradation of the hydrogel system, thereby achieving drug release, thereby completing the preparation of a dual drug release system. This method has strong operability, good timing control effect, long action time, low cost, and can realize the loading of different drugs for the treatment of various diseases, with broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0021] Figure 1 This is a scanning electron microscope (SEM) image of the magnesium peroxide particles prepared in Example 1 of the present invention;

[0022] Figure 2 This is a transmission electron microscope (TEM) image of the magnesium peroxide particles prepared in Example 1 of the present invention;

[0023] Figure 3 This is a SEM image of an implant with a surface that has been modified once, as prepared in Example 1 of the present invention;

[0024] Figure 4 This is a SEM image of a titanium-based implant with double surface modification prepared in Example 1 of the present invention;

[0025] Figure 5 This is a SEM picture of a titanium-based implant partially immersed in hydrogel and cross-linked prepared in Example 1 of the present invention, the left side is not immersed in hydrogel, and the right side is immersed in hydrogel;

[0026] Figure 6 This is a magnified SEM image of the surface of the titanium-based implant surface dual drug release system prepared in Example 1 of the present invention;

[0027] Figure 7 This is a result diagram of the photothermal conversion effect of the titanium-based implant with double surface modification prepared in Example 1 of the present invention;

[0028] Figure 8 This is the Mg ion release curve of the titanium-based implant with double surface modification prepared in Example 1 of the present invention;

[0029] Fig. 9 This is the Zn ion release curve of the titanium-based implant with double surface modification prepared in Example 1 of the present invention;

[0030] Fig.10 The curcumin release curve of the titanium-based implant with double surface modification prepared in Example 2 of the present invention;

[0031] Fig.11 The paclitaxel release curve of the titanium-based implant with double surface modification prepared in Example 3 of the present invention;

[0032] Fig.12 The results of the expression of osteogenic related genes in mesenchymal stem cells in the embodiment of the present invention are shown in Figure A. ALP Gene, B BMP-2 , C is Runx-2 , D is OPN , E is OCN , F is Col-I ;

[0033] Fig.13 Figure 1 is a graph showing the results of detecting the viability of osteosarcoma cells with and without near-infrared light irradiation in an embodiment of the present invention, A is without near-infrared light irradiation, and B is with near-infrared light irradiation;

[0034] Fig.14 This is a result diagram of bacterial plate coating in an embodiment of the present invention. DETAILED DESCRIPTION

[0035] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0036] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0037] In order to solve the problems of limited bonding ability between the titanium implant surface and the surrounding bone tissue and limited anti-tumor and anti-infection capabilities, the present invention proposes a titanium-based implant surface dual drug release system and a preparation method and application thereof.

[0038] A typical embodiment of the present invention provides a titanium-based implant surface dual drug release system, including a titanium-based implant and a hydrogel layer attached to the surface thereof, wherein the titanium-based implant surface is a nanotube array structure, zinc oxide nanoparticles and upconversion luminescent material particles are arranged between the titanium-based implant and the hydrogel layer, and MgO is loaded in the hydrogel layer. 2 Nanoparticles; wherein the material of the upconversion luminescent material particles is NaYF 4 : Yb 3+ , Er 3+ , the hydrogel layer is composed of gelatin-sodium alginate hydrogel.

[0039] In some embodiments, the titanium-based implant is a porous titanium-based implant. Specifically, the porous titanium-based implant is a three-periodic minimal surface structure. Specifically, the pore size of the porous titanium-based implant is 600-800 μm. Specifically, the porosity of the porous titanium-based implant is 65-75%.

[0040] In some embodiments, the titanium-based implant is a Ti-6Al-4V implant.

[0041] In some embodiments, the hydrogel layer is also loaded with active drugs, particularly, the active drugs include curcumin and / or paclitaxel.

[0042] Another embodiment of the present invention provides a method for preparing the above-mentioned dual drug release system on the surface of titanium-based implants, comprising the following steps:

[0043] Preparation of MgO 2 Nanoparticles, and MgO 2 Nanoparticles are loaded into the hydrogel;

[0044] The residual particles on the surface of the titanium-based implant are removed by acid etching and anodizing, and a nanotube array is constructed on the surface to obtain a pretreated titanium-based implant; the solution used in the anodizing method contains fluoride ions;

[0045] First, zinc oxide nanoparticles are deposited on the surface of a pretreated titanium-based implant, and then upconversion luminescent material particles are deposited on the surface of the pretreated titanium-based implant by a hydrothermal method to obtain a titanium-based implant with a double surface modification;

[0046] Loading MgO 2 The hydrogel of nanoparticles is coated on the surface of titanium-based implant to obtain the implant.

[0047] In some embodiments, MgO nanoparticles are reacted with hydrogen peroxide to form MgO 2 Nanoparticles. Specifically, MgO 2 The process of preparing the nanoparticles is carried out in an alcohol solvent. The alcohol solvent described in the present invention can be methanol, ethanol, isopropanol, etc. More specifically, the alcohol solvent is ethanol.

[0048] In some embodiments, the titanium-based implant is fabricated using selective laser melting (SLM) technology.

[0049] In some embodiments, the acid solution used in the acid etching method is a mixed solution of hydrofluoric acid and nitric acid.

[0050] In some embodiments, the anodization process is performed using a 24-26 V DC power supply.

[0051] In some embodiments, during the anodization process, the 4 F-glycerol aqueous solution was used for anodization.

[0052] In some embodiments, the process of depositing zinc oxide nanoparticles on the surface of a pretreated titanium-based implant is: immersing the pretreated titanium-based implant in a zinc salt solution, and then pyrolyzing the zinc salt to convert it into zinc oxide. Specifically, the pyrolysis conditions are: vacuum heating to 400-500 ° C. The zinc salt described in the present invention is a compound whose cation is a zinc ion, such as zinc nitrate, zinc sulfate, zinc acetate, etc. Specifically, the zinc salt used in the present invention is zinc acetate.

[0053] In some embodiments, the process of depositing upconversion luminescent material particles is: adding the pretreated titanium-based implant to a solution containing urea, yttrium salt, ytterbium salt and erbium salt, and heating it to 85-95°C for soaking, then adding it to a mixed solution containing NaF and HF, performing hydrothermal treatment, and then washing and drying. The hydrothermal treatment described in the present invention refers to a method of treating the reaction system under high pressure under closed conditions, using water as a solvent, and heating it. Specifically, the temperature of the hydrothermal treatment is 100-110°C. Specifically, the time of the hydrothermal treatment is 20-40 min. The yttrium salt described in the present invention refers to a compound whose cation is yttrium ion, such as yttrium nitrate, etc. The ytterbium salt described in the present invention refers to a compound whose cation is ytterbium ion, such as ytterbium nitrate, etc. The erbium salt described in the present invention refers to a compound whose cation is erbium ion, such as erbium nitrate, etc.

[0054] Specifically, the molar ratio of the yttrium salt, the ytterbium salt and the erbium salt is 200-300:60-70:5-10, preferably 240-260:60-65:5-7.

[0055] A third embodiment of the present invention provides an application of the above-mentioned dual drug release system on the surface of a titanium-based implant in the preparation of an implant material for treating osteosarcoma.

[0056] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0057] Example

[0058] A method for preparing a dual drug release system on a titanium-based implant surface, comprising the following steps:

[0059] MgO 2 Preparation method:

[0060] MgO nanoparticles were ultrasonically dispersed in anhydrous ethanol, and then hydrogen peroxide was added and stirred for 4 hours. The resulting solution was transferred to a centrifuge tube, centrifuged at high speed for 5 minutes, and then placed in a vacuum drying oven overnight. The resulting product is MgO 2 Nanoparticles.

[0061] Sample preparation method:

[0062] A porous Ti-6Al-4V implant (denoted as Ti) based on a three-periodic minimal surface with a pore size of 700 μm and a porosity of 70% was prepared using selective laser melting technology.

[0063] A mixed acid solution was prepared by mixing nitric acid with a mass concentration of 65%, hydrofluoric acid with a mass concentration of 40%, and water in a volume ratio of 31:5:64. The implant was subjected to flow acid etching for 90 s using the mixed acid solution. 4 F-Propylene glycol aqueous solution (NH 4 The concentration of F is 0.27 mol·L -1 The pretreated implant was anodized in 4% paraformaldehyde (PVA), with the volume ratio of glycerol to water being 1:1) for 1 h and dried to obtain the pretreated implant.

[0064] The pretreated implant (10×10×2 mm 3 ) was immersed in 50 mL 0.3mmol·L -1 The implant was taken out of the zinc acetate solution and heated at 450 °C in vacuum for 2 h to obtain an implant with a single surface modification (denoted as Ti-Zn).

[0065] 0.25 g urea was dissolved in 25 mL deionized water, and then 250 μL of 1.0 M Y(NO 3 ) 3 , 100 μL Yb(NO 3 ) 3 and 15 μL of 0.4 M Er(NO 3 ) 3 , and obtain a rare earth mixed solution.

[0066] The implant with the first surface modification was placed in a rare earth mixture and immersed in a 90°C water bath for 3 h. After removal, 20 mL of NaF (0.01 g mL -1 ) and HF (0.03 mol·L -1 ) mixed solution, placed in a 30 mL hydrothermal reactor, hydrothermally treated at 100 °C for 30 min, taken out, ultrasonically cleaned in deionized water and dried in air to obtain a titanium-based implant with dual surface modification.

[0067] Prepare gelatin-sodium alginate hydrogel: weigh 0.5 g gelatin and 0.125 g sodium alginate, then weigh 100 μg MgO 2 The nanoparticles were dissolved in 5 mL of deionized water by heating and stirring. After the hydrogel cooled, the double-modified titanium-based implant was immersed in the hydrogel for 5 minutes and 2% CaCl 2The solution was cross-linked at room temperature for 5 minutes to complete the filling of the hydrogel on the surface and inside of the implant (denoted as Ti-Zn-Mg).

[0068] The magnesium peroxide particles synthesized in this embodiment are as follows Figure 1~2 As shown, it is shown that the particle size of the magnesium peroxide particles synthesized in this example is about 80 nm.

[0069] like Figure 3 As shown, the implant of this embodiment forms orderly arranged nanotubes after acid etching and anodizing, and ZnO nanoparticles are formed around the nanotubes.

[0070] like Figure 4 As shown, in the titanium-based implant with double surface modification prepared in this embodiment, cube-shaped rare earth element particles are deposited on the surface of the nanotubes.

[0071] In order to show the difference before and after coating with hydrogel, another part of the titanium-based implant with double surface modification was immersed in hydrogel for 5 minutes using 2% CaCl 2 Solution, crosslinked at room temperature for 5 minutes, the result is as Figure 5 As shown in the figure, the left side is without gel, and the right side is with gel. It is observed that the residual particles in the 3D printing process are completely removed, and micron-scale pits are formed on the surface. In addition, a loose and porous structure is formed after adding gel, which proves that the gel is filled into the porous implant. At the same time, the hydrogel has a large specific surface area and forms larger pores, such as Figure 6 shown.

[0072] Example 2

[0073] The same as Example 1, except that 75 μg of curcumin was further added to the hydrogel.

[0074] Example 3

[0075] The same as Example 1, except that 17 μg of paclitaxel was further added to the hydrogel.

[0076] Performance Testing:

[0077] Surface temperature monitoring:

[0078] The titanium-based implant with double surface modification prepared in Example 1 was irradiated with near infrared light (wavelength 808 nm) to detect its photothermal conversion effect. The results are as follows: Figure 7 As shown, the results show that under the irradiation of near-infrared light, the surface temperature rises, photothermal conversion is achieved, and the temperature finally stabilizes at around 53°C.

[0079] Drug release testing:

[0080] Experimental method: To evaluate the ion and drug release behavior of the samples, the samples were placed in 1 mL of PBS solution at 37°C for 60 days, and one group of samples was irradiated with 808 nm near-infrared light for 10 minutes every day. The ion and drug release behavior of the samples were evaluated every 3 days. Zn was measured using inductively coupled plasma mass spectrometry. 2+ and Mg 2+ Determination of release concentration. For curcumin and paclitaxel, the loading amount of the drug on the surface can be determined by calculation. For curcumin, the absorbance is measured at 428nm using a UV-visible spectrophotometer. For paclitaxel, it is measured at 230nm. The release concentration is characterized by the obtained standard curve.

[0081] The results are as follows Figures 8 to 11 As shown in the figure, after adding photothermal, the release rate of Mg was significantly improved, the first release effect was ended in advance, and the release effect of curcumin and paclitaxel was the same as that of Mg. In addition, under the action of photothermal, the second drug (i.e. zinc) was released in advance and the release result was achieved in advance, as shown in the figure. Fig. 9 shown.

[0082] RT-qPCR detection of mesenchymal stem cell osteogenesis-related genes:

[0083] Experimental method: cells were cultured at 1×10 5 cells / mL were inoculated on the sample surface. After 7 and 14 days of culture, the cells on the sample surface were washed with PBS. 600 μL Trizol was added to each sample well to lyse the cells. The RNA concentration was measured at 260 / 280 nm using a spectrophotometer. Afterwards, the RNA was converted into cDNA using a reverse transcription kit. ALP , OCN , Col-I , BMP-2 , OPN and Runx-2 As the target gene for detection, and select GAPDH The expression level of the target gene was standardized as an internal reference gene. Real-time fluorescence quantitative PCR was used for detection, and the relative quantitative comparison method (2 -ΔΔCT method) to calculate and analyze sample results.

[0084] The results are as follows Fig.12 As shown, under the action of the dual release system, the expression of osteogenic-related genes in mesenchymal stem cells was significantly enhanced, which was helpful for the next step of new bone formation.

[0085] CCK-8 method to detect cell viability of osteosarcoma cells:

[0086] Experimental method: cells were cultured at 2×104 The cells / mL density was inoculated in a 24-well plate with a size of 10×10×2 mm 3 The porous sample surface was placed on the plate. After 1, 4, and 7 days of culture, the samples were transferred to new sample wells, and 1 mL of culture medium and 100 μL of CCK-8 dye were added to the wells. After incubation in a 37°C incubator for 1 hour, 200 μL of liquid was aspirated and transferred to a 96-well plate. The absorbance of each group of samples was detected at 450 nm using an ELISA reader.

[0087] The results are as follows Fig.13 As shown, in the absence of near-infrared irradiation, MgO is slowly released 2 The cell viability is reduced, and under the irradiation of near-infrared light, the surface temperature increases, the degradation and release of the hydrogel are accelerated, and at the same time, under the treatment of photothermal and photodynamic therapy, the viability of tumor cells is significantly reduced.

[0088] Bacterial plate spreading

[0089] Experimental method: The 24-well plate inoculated with bacterial solution was placed in a 37°C constant temperature incubator for 24 hours. The concentration of the bacterial solution was 1×10 5 CFU·mL -1 , then transfer the sample to a new sample well, add 1 mL of PBS to each well, and blow the live bacteria off the surface. Then dilute the obtained solution 10 times with PBS. After that, add the liquid dropwise to the culture dish containing LB solid culture medium, and use a sterilized glass curved rod to spread the liquid evenly. Place the culture dish in a 37°C constant temperature incubator for 12 hours, take it out and take a photo to observe the colony size.

[0090] The results are as follows Fig.14 As shown, MgO 2 The particles significantly inhibited bacterial growth, and under the action of photothermal therapy and gel accelerated release, the colony formation area was further significantly reduced.

[0091] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A dual drug release system on the surface of a titanium-based implant, characterized in that: The invention comprises a titanium-based implant and a hydrogel layer attached to the surface thereof, wherein the surface of the titanium-based implant is a nanotube array structure, zinc oxide nanoparticles and upconversion luminescent material particles are arranged between the titanium-based implant and the hydrogel layer, and MgO2 nanoparticles are loaded in the hydrogel layer; wherein the material of the upconversion luminescent material particles is NaYF4: Yb 3+ , Er 3+ , the hydrogel layer is composed of gelatin-sodium alginate hydrogel.

2. The titanium-based implant surface dual drug release system as claimed in claim 1, characterized in that: The titanium-based implant is a porous titanium-based implant.

3. The titanium-based implant surface dual drug release system as claimed in claim 1, characterized in that: The titanium-based implant is a Ti-6Al-4V implant.

4. The titanium-based implant surface dual drug release system as claimed in claim 1, characterized in that: The hydrogel layer is also loaded with active drugs; the active drugs include curcumin and / or paclitaxel.

5. A method for preparing a dual drug release system on a titanium-based implant surface according to any one of claims 1 to 4, characterized in that: The steps include: preparing MgO2 nanoparticles and loading the MgO2 nanoparticles into the hydrogel; The residual particles on the surface of the titanium-based implant are removed by acid etching and anodizing, and a nanotube array is constructed on the surface to obtain a pretreated titanium-based implant; the solution used in the anodizing method contains fluoride ions; First, zinc oxide nanoparticles are deposited on the surface of a pretreated titanium-based implant, and then upconversion luminescent material particles are deposited on the surface of the pretreated titanium-based implant by a hydrothermal method to obtain a titanium-based implant with a double surface modification; The hydrogel loaded with MgO2 nanoparticles is coated on the surface of a titanium-based implant to obtain the implant.

6. The preparation method according to claim 5, characterized in that: MgO nanoparticles are prepared by double decomposition reaction with hydrogen peroxide to form MgO2 nanoparticles; Alternatively, titanium-based implants can be fabricated using selective laser melting technology.

7. The preparation method according to claim 5, characterized in that: The acid solution used in the acid etching method is a mixed solution of hydrofluoric acid and nitric acid; Or, the anodic oxidation method is carried out using a 24-26V DC power supply; Alternatively, in the anodizing method, anodizing treatment is performed in an NH4F-glycerol aqueous solution.

8. The preparation method as claimed in claim 5, characterized in that The process of depositing zinc oxide nanoparticles on the surface of a pretreated titanium-based implant is as follows: immersing the pretreated titanium-based implant in a zinc salt solution, and then pyrolyzing the zinc salt to convert it into zinc oxide.

9. The preparation method according to claim 5, characterized in that: The process of depositing upconversion luminescent material particles is as follows: adding the pretreated titanium-based implant into a solution containing urea, yttrium salt, ytterbium salt and erbium salt, heating it to 85-95°C for soaking, then adding it into a mixed solution containing NaF and HF for hydrothermal treatment, and then washing and drying.

10. Use of the dual drug release system on the surface of a titanium-based implant according to any one of claims 1 to 4 in the preparation of an implant material for treating osteosarcoma.

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