Metal organic framework, preparation method and application thereof

Abstract

According to the metal organic framework constructed on the titanium metal surface and the preparation method, the titanate is formed on the titanium alloy surface through alkali treatment, on the basis, polyvinylpyrrolidone is used for modifying the titanate, then metal zinc ions and organic ligands are used for alternately treating the surface, and the metal organic framework is obtained. The metal organic framework prepared by the preparation method disclosed by the invention grows on the surface of the titanium alloy in situ, nucleation and a substrate have relatively good binding force, and the metal organic framework has a relatively good drug loading function and has a wide application prospect in the biomedical field.

Description

Technical Field

[0001] The present application relates to the technical field of biomedical materials, and in particular to a method for constructing a metal organic framework on a titanium metal surface, a metal organic framework and applications thereof. Background Art

[0002] Titanium alloys have excellent biocompatibility and mechanical properties and are widely used in the research and development of bone implant materials. However, due to its biological inertness, it cannot form bone integration with surrounding tissues after implantation, and is prone to aseptic loosening, leading to implant failure. Metal-organic framework (MOFs) materials with many excellent properties have great prospects in improving the functionalization of biomaterials. Specifically, MOFs are a class of porous hybrid materials synthesized by coordination of metal ions / clusters and organic ligands. Compared with other porous materials, MOFs are characterized by their highly tunable composition because abundant metal ions / clusters and organic ligands can be utilized. In addition, MOFs have a high specific surface area and adjustable pore structure, which allows guest molecules to be captured, loaded and transported, and helps to improve ion transport capacity and catalytic activity. Many studies have attempted to construct metal-organic frameworks in situ on the surface of titanium alloys to improve the bone integration performance of titanium alloys.

[0003] Junyu Chen prepared Zn-based MOF films composed of zeolitic imidazolate framework-8 (ZIF-8) crystals (nanoZIF-8 and microZIF-8) composed of nano- and micro-sized crystals (nanoZIF-8 and microZIF-8) on porous titanium surfaces by hydrothermal and solvothermal methods, respectively. The nanoZIF-8 films showed good biocompatibility to MG63 cells, while the microZIF-8 films showed significant cytotoxicity to MG63 cells. Compared with pure titanium and porous titanium treated with alkali and heat, the nanoZIF-8 films not only enhanced the alkaline phosphatase (ALP) activity, extracellular matrix mineralization and the expression of osteogenic genes (ALP, Runx2) in MG63 cells, but also inhibited the growth of Streptococcus mutans, but this growth mode was homogeneous nucleation and weakly bound to the substrate. Summary of the invention

[0004] In view of this, it is necessary to provide a method for constructing a metal organic framework on a titanium metal surface with good bonding between the nucleus and the substrate, a metal organic framework and its application in order to address the current technical defects of weak bonding between the nucleus and the substrate in constructing a metal organic framework on a titanium metal surface.

[0005] To solve the above problems, this application adopts the following technical solutions:

[0006] One of the purposes of the present application is to provide a method for constructing a metal organic framework on a titanium metal surface, comprising the following steps:

[0007] Formation of titanate on the surface of titanium metal;

[0008] The titanate is modified with polyvinyl pyrrolidone (pvp);

[0009] The modified titanate is treated alternately with metal ions and organic ligands to in-situ grow a metal organic framework on the titanium metal surface.

[0010] In some embodiments, the step of forming titanate on the surface of titanium metal specifically includes the following steps:

[0011] Titanium metal and an alkaline solution are mixed and reacted to form titanate on the surface of the titanium metal. The titanium metal includes titanium or a titanium alloy. The alkaline solution includes NaOH. The reaction temperature is 60° C. and the reaction time is 12 to 36 hours.

[0012] In some embodiments, the step of modifying the titanate with polyvinyl pyrrolidone specifically includes the following steps:

[0013] The titanium metal with titanate formed on the surface is mixed with a polyvinyl pyrrolidone solution for reaction for 12 to 36 hours, and then washed and dried naturally to obtain polyvinyl pyrrolidone-modified titanate.

[0014] In some embodiments, the modified titanate is treated alternately with metal ions and organic ligands to in-situ grow a metal organic framework on the titanium metal surface, specifically comprising the following steps:

[0015] The polyvinyl pyrrolidone-modified titanate is mixed with a metal zinc ion solution and treated for 1 to 4 hours;

[0016] The treated titanate is washed and mixed with the organic ligand for 1 to 4 hours;

[0017] The treated titanate is cleaned and dried to in-situ grow a metal organic framework on the titanium metal surface.

[0018] In some embodiments, the metal zinc ion solution includes zinc nitrate or cobalt nitrate, and the organic ligand includes 2-methylimidazole.

[0019] In some embodiments, the metal organic framework is ZIF-8.

[0020] The second purpose of the present application is to provide a metal organic framework, including one prepared by the method described.

[0021] The third purpose of the present application is to provide an application of the metal organic framework in drug loading.

[0022] This application adopts the above technical solution, and its beneficial effects are as follows:

[0023] The present application provides a method for constructing a metal-organic framework on a titanium metal surface and a preparation method thereof, wherein titanate is formed on the titanium alloy surface by alkali treatment, and on this basis, the titanate is modified by using polyvinyl pyrrolidone, and then its surface is alternately treated with metal zinc ions and organic ligands to in situ grow a metal-organic framework on the titanium alloy surface. The metal-organic framework prepared by the present invention grows in situ on the titanium alloy surface, has good nucleation and substrate bonding, has good drug loading function, and has broad application prospects in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments of the present application or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0025] Figure 1 A flowchart of the steps of the method for constructing a metal organic framework on a titanium metal surface provided in an embodiment of the present application.

[0026] Figure 2 This is a SEM morphology image of titanate (HT) formed on the surface of titanium metal provided in Example 1 of the present application.

[0027] Figure 3 HT-ZIF-8③ is the SEM morphology of HT modified with PVP for 24 hours and HT treated alternately with 25mM Zn ions and 200mM 2-MIM + 10ul 1M ammonia water for 1 hour as provided in Example 1 of the present application.

[0028] Figure 4 This is the SEM morphology of the PVP-modified HT provided in Example 1 of the present application for 36 hours and the HT treated alternately with 25 mM Zn ions and 200 mM 2-MIM + 2 ul 1 M ammonia water for 1 hour.

[0029] Figure 5 This is the SEM morphology of the rBMSCs provided in Example 1 of the present application after being inoculated on HT-ZIF-8② and cultured for 48 hours.

[0030] Figure 6 The polarization of macrophages observed by immunofluorescence after 48 hours of culture on HT-ZIF-8 / IL-4 and HT-ZIF-8 / IL-4 provided in Example 1 of the present application. DETAILED DESCRIPTION

[0031] Embodiments of the present application are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present application, and should not be construed as limiting the present application.

[0032] In the description of the present application, it should be understood that the terms "upper", "lower", "horizontal", "inside", "outside", etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

[0033] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0034] In order to make the objectives, technical solutions and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments.

[0035] See also Figure 1 , which is a step flow chart of the method for constructing a metal organic framework on a titanium metal surface provided in an embodiment of the present application, including the following steps S110 to S130, and the technical solution for its implementation is described in detail below.

[0036] Step S110: forming titanate on the surface of titanium metal.

[0037] In this embodiment, the step of forming titanate on the surface of titanium metal specifically includes the following steps:

[0038] Titanium metal and an alkaline solution are mixed and reacted to form titanate on the surface of the titanium metal. The titanium metal includes titanium or a titanium alloy. The alkaline solution includes NaOH. The reaction temperature is 60° C. and the reaction time is 12 to 36 hours.

[0039] Step S120: modifying the titanate with polyvinyl pyrrolidone.

[0040] In this embodiment, the step of modifying the titanate with polyvinyl pyrrolidone specifically includes the following steps: mixing the titanium metal with titanate formed on the surface with the polyvinyl pyrrolidone solution for reaction for 12 to 36 hours, and then washing and drying naturally to obtain the polyvinyl pyrrolidone-modified titanate.

[0041] Step S130: treating the modified titanate with metal ions and organic ligands alternately to in-situ grow a metal-organic framework on the titanium metal surface.

[0042] In this embodiment, the modified titanate is treated alternately with metal ions and organic ligands to in-situ grow a metal organic framework on the titanium metal surface, specifically comprising the following steps:

[0043] The polyvinyl pyrrolidone-modified titanate is mixed with a metal zinc ion solution for 1 to 4 hours; the treated titanate is washed and mixed with an organic ligand for 1 to 4 hours; the treated titanate is washed and dried to in-situ grow a metal organic framework on the titanium metal surface.

[0044] In this embodiment, the metal zinc ion solution includes zinc nitrate or cobalt nitrate, the organic ligand includes 2-methylimidazole, and the metal organic framework is ZIF-8.

[0045] It can be understood that the size and morphology of the metal organic framework grown on the titanium metal surface provided in the above embodiments of the present application are adjustable and can be customized according to drug loading requirements.

[0046] The present application provides a method for constructing a metal-organic framework on a titanium metal surface and a preparation method thereof, wherein titanate is formed on the titanium alloy surface by alkali treatment, and on this basis, the titanate is modified by using polyvinyl pyrrolidone, and then its surface is alternately treated with metal zinc ions and organic ligands to in situ grow a metal-organic framework on the titanium alloy surface. The metal-organic framework prepared by the present invention grows in situ on the titanium alloy surface, has good nucleation and substrate bonding, has good drug loading function, and has broad application prospects in the biomedical field.

[0047] The above technical solution of the present application is described in detail below in conjunction with specific embodiments.

[0048] Example

[0049] (1) Preparation, configuration and precautions of each solution and reagent

[0050] a. Sodium hydroxide solution (concentration: 5M): weigh 10g sodium hydroxide and dissolve it in 50ml ultrapure water (deionized water is also acceptable, the same below). Note: It is easy to lose its effectiveness if stored for a long time, and the usage time should not exceed 1 month.

[0051] b. Polyvinylpyrrolidone (PVP) (3% wt): Weigh 0.3 g of PVP powder and dissolve it in 10 ml of anhydrous ethanol. Note: Anhydrous ethanol is very volatile, so use the solution quickly each time, cover the bottle cap in time, and seal it with a sealing film.

[0052] c. Zinc nitrate solution (25mM): Weigh 0.371g of Zn(NO3)2·6H2O and dissolve it in distilled water. After it is completely dissolved, adjust the volume to 50ml. Note: Zinc nitrate absorbs water seriously. During the weighing process, the surrounding environment must be kept dry and the action must be quick. After weighing, seal it and store it in a drying cabinet.

[0053] d. Dimethylimidazole solution (200mM): Weigh 0.821g of dimethylimidazole and dissolve it in distilled water. After it is completely dissolved, adjust the volume to 50ml. Note: Dimethylimidazole easily absorbs water. During the weighing process, the surrounding environment must be kept dry and the action must be quick. After weighing, seal it and store it in a drying cabinet.

[0054] (2) Alkali treatment of titanium alloy to form titanate

[0055] a. Take 7 titanium alloy discs with a diameter of 1.2 cm, clean them ultrasonically, place them in a reactor, add 50 ml 5M NaOH, react in an oven at 60°C for 24 hours, and ultrasonically clean them with anhydrous ethanol and distilled water for 5 minutes respectively to obtain titanate, which is then dried for later use.

[0056] (3) PVP modification of titanate

[0057] a. Take three alkali-treated titanium alloys and place them in a 6-well plate, add 3 ml of 3% PVP solution and react for 24 hours, wash three times with distilled water, and dry naturally for 24 hours to obtain PVP-modified titanate.

[0058] (4) In situ growth of metal organic framework ZIF-8 on titanate surface

[0059] a. Place the PVP-modified titanate in a 24-well plate, add 1 mL of 25 mM zinc nitrate for 1 h, wash twice with distilled water, then add 1 mL of 200 mM 2-methylimidazole for 1 h, wash twice with distilled water, and blow dry with cold air from a hair dryer.

[0060] See also Figure 2 , is a SEM morphology of titanate (HT) formed on the titanium metal surface provided in Example 1, Figure 2 From left to right in the figure are: SEM morphology of HT formed on the titanium metal surface ( Figure 2 HT (shown in Figure 1) was modified with PVP for 24 h and then treated with Zn ion and imidazole exchange ( Figure 2 HT-ZIF-8① in the figure); PVP modified HT for 24h, and then added 2μl 1M ammonia water ( Figure 2 (shown in HT-ZIF-8②).

[0061] from Figure 2 It can be seen that the HT formed by alkali-treated titanium alloy presents a nanofiber structure. After HT is modified by PVP and then treated alternately with Zn ions and imidazole, ZIF-8 nanomaterials are grown in situ on the nanofibers. After the addition of ammonia water for adjustment, the nanomaterials are significantly reduced.

[0062] See also Figure 3 , which is the SEM morphology of HT modified with PVP for 24h and HT treated with 25mM Zn ions and 200mM 2-MIM + 10ul 1M ammonia water for 1h provided in Example 1 HT-ZIF-8③( Figure 3 ).

[0063] In order to verify the effect of ammonia on the growth of nanomaterials, the volume of ammonia was increased from 2 μl to 10 μl. Figure 3 It can be seen that when the amount of ammonia water increases, the growth of nanomaterials increases significantly and grows in a flake-like manner.

[0064] See also Figure 4 , which is the SEM morphology of the PVP-modified HT provided in Example 1 for 36 h and the HT treated with 25 mM Zn ions and 200 mM 2-MIM + 2 ul 1 M ammonia water for 1 h ( Figure 4 ).

[0065] In order to verify the effect of PVP treatment time on the growth of nanomaterials, the PVP treatment time was extended from 24 h to 36 h. As can be seen from Figure 4, when the PVP treatment time was extended, the nanomaterials grew more and more densely on the titanate.

[0066] See also Figure 5 , is the SEM morphology of the rBMSCs provided in Example 1 after being inoculated on HT-ZIF-8② and cultured for 48 hours.

[0067] In order to verify the biocompatibility of HT-ZIF-8 nanomaterials, rat mesenchymal stem cells (rBMSCs) were seeded on HT-ZIF-8② and incubated for 48 h. Figure 5 It can be seen that the cells spread well on the surface of the material, and the ZIF-8 nanomaterials grown on the titanate nanofibers are still retained. Therefore, it is expected to give titanium implants good drug loading capabilities and thus regulate cell behavior.

[0068] See also Figure 6 Immunofluorescence was used to observe the polarization of macrophages after they were cultured on HT-ZIF-8 / IL-4 and HT-ZIF-8 / IL-4 for 48 h.

[0069] In order to verify that the HT-ZIF-8② drug-loading platform can load drugs to regulate cell behavior, HT-ZIF-8② was treated with 100ng / ml IL-4 for 24h to obtain HT-ZIF-8 / IL-4, and then macrophages RAW264.7 were inoculated on the surface of the material to examine the polarization behavior of macrophages after 48h of culture. Figure 6 It can be seen that compared with the unloaded HT-ZIF-8 in the control group, loading IL-4 on the material can significantly promote the expression of macrophage M2 marker protein Arg and inhibit the expression of macrophage M1 marker protein M1. Studies have reported that macrophage polarization to M2 is expected to promote cell osteogenic differentiation. Therefore, the results show that HT-ZIF-8 / IL-4 can regulate the polarization of immune cells (macrophages) from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. HT-ZIF-8 can be used as a carrier for titanium alloy surface modification to regulate the behavior of macrophages, thereby improving their osteogenic effect.

[0070] The above are only preferred embodiments of the present application, and only specifically describe the technical principles of the present application. These descriptions are only for explaining the principles of the present application and cannot be interpreted as limiting the scope of protection of the present application in any way. Based on the explanation here, any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application, and other specific implementation methods of the present application that can be associated with the technicians in this field without creative work, should be included in the scope of protection of the present application.

Claims

1. A method for constructing a metal organic framework on a titanium metal surface, characterized in that: The steps include: Formation of titanate on the surface of titanium metal; Modifying the titanate with polyvinyl pyrrolidone; The modified titanate is treated alternately with metal ions and organic ligands to in-situ grow a metal organic framework on the titanium metal surface.

2. The method for constructing a metal organic framework on a titanium metal surface according to claim 1, characterized in that: The step of forming titanate on the titanium metal surface specifically includes the following steps: Titanium metal and an alkaline solution are mixed and reacted to form titanate on the surface of the titanium metal. The titanium metal includes titanium or a titanium alloy. The alkaline solution includes NaOH. The reaction temperature is 60° C. and the reaction time is 12 to 36 hours.

3. The method for constructing a metal organic framework on a titanium metal surface according to claim 1, characterized in that: The step of modifying the titanate with polyvinyl pyrrolidone specifically includes the following steps: The titanium metal with titanate formed on the surface is mixed with a polyvinyl pyrrolidone solution for reaction for 12 to 36 hours, and then washed and dried naturally to obtain polyvinyl pyrrolidone-modified titanate.

4. The method for constructing a metal organic framework on a titanium metal surface according to claim 1, characterized in that: The modified titanate is treated alternately with metal ions and organic ligands to in-situ grow a metal organic framework on the titanium metal surface, specifically comprising the following steps: The polyvinyl pyrrolidone-modified titanate is mixed with a metal zinc ion solution and treated for 1 to 4 hours; The treated titanate is washed and mixed with the organic ligand for 1 to 4 hours; The treated titanate is cleaned and dried to in-situ grow a metal organic framework on the titanium metal surface.

5. The method for constructing a metal organic framework on a titanium metal surface as claimed in claim 4, characterized in that: The metal zinc ion solution includes zinc nitrate or cobalt nitrate, and the organic ligand includes 2-methylimidazole.

6. The method for constructing a metal organic framework on a titanium metal surface according to claim 5, characterized in that: The metal organic framework is ZIF-8.

7. A metal organic framework, characterized in that The method comprises preparing the product by the method described in any one of claims 1 to 6.

8. Use of the metal organic framework as claimed in claim 7 in drug loading.

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