Bone cement with fluorescence imaging function and application
By using aggregate-induced luminescence functionalized mesoporous nanoparticles in bone cement for fluorescence imaging, the radiation damage and biocompatibility of X-ray developers to the human body is solved, and a safe and efficient detection method is provided to meet clinical needs. .
Patent Information
- Application Number
- CN202411355571.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-27
- Publication Date
- 2024-12-27
AI Technical Summary
The X-ray developer materials in existing bone cement cause radiation damage and biocompatibility problems to the human body, affecting the mechanical properties and service life of bone cement.
Functionalized mesoporous nanoparticles of aggregate-induced luminescence are used as fluorescent imaging agents, instead of traditional X-ray developer, bone cement detection is carried out through fluorescence imaging technology to avoid the hazards of X-ray radiation and improve biocompatibility.
It achieves avoiding X-ray hazards and improving biocompatibility without affecting the mechanical properties of bone cement, and provides a safe and efficient fluorescence imaging detection method to meet clinical needs.
Smart Images
Figure CN119185644A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of biomaterials, and in particular to bone cement with fluorescence imaging function and application thereof. Background Art
[0002] At present, the developer materials used in bone cement are mainly metal inorganic salt compounds such as BaSO4 or ZrO2, which can achieve good development effects in X-ray imaging. However, X-ray imaging has radiation damage, and the above materials may cause adverse harm to the human body such as neurotoxicity and cell deformation, and cannot form an effective whole in bone cement. They are easily separated from bone cement, thereby affecting the mechanical properties of bone cement, which may cause wear and loosening of artificial joints and shorten the service life of artificial joints. Therefore, how to improve the radiation hazards caused by X-ray imaging and the biocompatibility of the developer is an urgent problem to be solved.
[0003] In view of this, the present invention is proposed. Summary of the invention
[0004] The purpose of the present invention is to provide an application of aggregation-induced luminescence functionalized mesoporous nanoparticles in bone cement fluorescence imaging, so as to alleviate the technical problems of radiation hazards caused by X-ray imaging and poor biocompatibility of the developer existing in the prior art.
[0005] The second object of the present invention is to provide a method for fluorescence imaging of bone cement, in order to use fluorescence imaging functional molecules to replace existing developer, thereby avoiding the use of X-rays for bone cement imaging detection.
[0006] The third object of the present invention is to provide a bone cement with fluorescence imaging function, so that the bone cement can be detected by fluorescence detection means instead of X-ray detection means, thereby avoiding the harm of X-ray detection.
[0007] The fourth object of the present invention is to provide the use of the above-mentioned bone cement with fluorescence imaging function in the preparation of hard tissue repair products.
[0008] In order to solve the above technical problems and achieve the above objectives, the present invention provides the following technical solutions:
[0009] In a first aspect, the present invention provides an application of aggregation-induced emission functionalized mesoporous nanoparticles in fluorescence imaging of bone cement for non-diagnostic purposes.
[0010] Fluorescence molecular imaging technology plays an increasingly important role in in vivo disease observation, drug and biological research with its advantages of low cost, simplicity and ease of use, and no ionizing radiation to organisms. However, traditional organic fluorescent pigments will show serious fluorescence self-quenching after aggregation at high concentrations. The new fluorescent pigments discovered in recent years produce aggregation-induced emission (AIE) phenomenon after aggregation at high concentrations due to restricted intramolecular motion, suppressed non-radiative channels, and energy released in the form of light energy, thus overcoming the disadvantage of fluorescence quenching. However, currently, aggregation-induced emission functional materials are mostly used in sensing detection and drug controlled release. The present invention first uses aggregation-induced emission functional materials to functionalize mesoporous nanoparticles, and then applies them to the development detection of bone cement for non-diagnostic purposes.
[0011] In a second aspect, the present invention provides a method for fluorescence imaging of bone cement, the method comprising adding a developer to the bone cement, wherein the developer comprises aggregation-induced emission functionalized mesoporous nanoparticles.
[0012] Aggregation-induced emission functionalized mesoporous nanoparticles are used as developers to perform fluorescence imaging of bone cement. Compared with the existing bone cement imaging technology, this can avoid the radiation hazards caused by X-ray imaging and ensure that the biocompatibility of bone cement is not affected.
[0013] In an optional embodiment, the aggregation-induced emission functionalized mesoporous nanoparticles include aggregation-induced emission functionalized mesoporous silica nanoparticles.
[0014] Mesoporous silica materials have regular and ordered mesoporous structures, adjustable pore sizes, modifiable surface properties, good biocompatibility and other characteristics, making them a good carrier for loading fluorescent sensing molecules. By grafting fluorophores onto the surface of mesoporous materials, the application range of inorganic mesoporous silica can be expanded, and the optical sensitivity of fluorophores can be significantly improved, providing a good choice for constructing new optical sensors with high sensitivity and fast response.
[0015] In a third aspect, the present invention provides a bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises aggregation-induced emission functionalized mesoporous nanoparticles.
[0016] Preferably, the aggregation-induced emission functionalized mesoporous nanoparticles include aggregation-induced emission functionalized mesoporous silica nanoparticles.
[0017] AIE functionalized mesoporous silica material combines the dual advantages of porous structure and AIE fluorescent group. When applied to bone cement, it can be used to observe the condition of bone cement at the surgical site by fluorescence imaging, thereby improving the radiation problem caused by X-ray imaging. At the same time, the addition of AIE functionalized mesoporous silica improves the poor biocompatibility of traditional inorganic salt compounds.
[0018] In an optional embodiment, the powder component further includes polymethyl methacrylate and an initiator, and the liquid component includes methyl methacrylate monomer, a promoter and an inhibitor.
[0019] Preferably, the initiator comprises benzoyl peroxide.
[0020] Preferably, the accelerator comprises N,N-dimethyl-p-toluidine.
[0021] Preferably, the polymerization inhibitor comprises hydroquinone.
[0022] In an optional embodiment, the powder component includes, by mass percentage, 88.5% to 90.5% of polymethyl methacrylate, 0.4% to 0.6% of benzoyl peroxide and 9% to 11% of aggregation-induced emission functionalized mesoporous silica nanoparticles.
[0023] Preferably, the powder component comprises, by mass percentage, 89.5% of polymethyl methacrylate, 0.5% of benzoyl peroxide and 10% of aggregation-induced luminescence functionalized mesoporous silica nanoparticles.
[0024] In an optional embodiment, the liquid component includes, by mass percentage, 97% to 98% of methyl methacrylate monomer, 1.5% to 2.5% of N,N-dimethyl-p-toluidine and 0.5% to 1% of hydroquinone.
[0025] Preferably, the liquid component comprises, by mass percentage, 97.5% of methyl methacrylate monomer, 2.0% of N,N-dimethyl-p-toluidine and 0.5% of hydroquinone.
[0026] In an optional embodiment, the mass ratio of the powder component to the liquid component is (2-2.2):1, preferably a mass ratio of 2:1.
[0027] In an optional embodiment, the method for preparing the aggregation-induced emission functionalized mesoporous silica nanoparticles comprises heating the mesoporous silica nanoparticles and functional molecules having aggregation-induced emission in a solvent to obtain the aggregation-induced emission functionalized mesoporous silica nanoparticles.
[0028] Preferably, the functional molecule having aggregation-induced emission comprises tetraphenylethylene.
[0029] Preferably, the solvent comprises acetonitrile.
[0030] Preferably, the mass ratio of the mesoporous silica nanoparticles to the functional molecules having aggregation-induced emission is (1-1.67):1.
[0031] Preferably, the amount of the mesoporous silica nanoparticles is 20-25 mg, and the amount of the functional molecules having aggregation-induced emission is 15-20 mg.
[0032] Preferably, the heating temperature is 50-70° C., and the heating time is 2-4 hours.
[0033] Preferably, the method for preparing the mesoporous silica nanoparticles comprises adding ethyl orthosilicate dropwise to a template agent and then heating at a constant temperature to prepare the mesoporous silica nanoparticles.
[0034] Preferably, the templating agent comprises an alkaline solution of hexadecyltrimethylammonium bromide.
[0035] In a fourth aspect, the present invention provides use of the bone cement described in any one of the aforementioned embodiments in the preparation of a hard tissue repair product.
[0036] The present invention provides an application of aggregation-induced emission functionalized mesoporous nanoparticles in fluorescence imaging of bone cement for non-diagnostic purposes. AIE functionalized mesoporous silica material combines the dual advantages of porous structure and AIE fluorescent group. When applied to bone cement, the condition of bone cement at the surgical site can be observed by fluorescence imaging, thereby improving the radiation problem caused by X-ray imaging. At the same time, the addition of AIE functionalized mesoporous silica improves the problem of poor biocompatibility of traditional inorganic salt compounds. BRIEF DESCRIPTION OF THE DRAWINGS
[0037] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.
[0038] Figure 1 Effects of the bone cement provided in Example 2 and Comparative Example 1 of the present invention on cell proliferation;
[0039] Figure 2 This is an electron microscope image of mesoporous silica;
[0040] Figure 3 The fluorescence imaging performance comparison of Examples 1 and 2 is shown in FIG. DETAILED DESCRIPTION
[0041] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Generally, the components of the embodiments of the present invention described and shown in the drawings here can be arranged and designed in various different configurations.
[0042] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0043] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, further definition and explanation thereof is not required in subsequent drawings.
[0044] In a specific embodiment, the present invention provides a method for preparing AIE functionalized mesoporous silica nanoparticles, which specifically comprises the following steps:
[0045] (1) Using surfactant hexadecyltrimethylammonium bromide (CTAB) as a template, add 200-500 mg of CTAB into an appropriate amount of deionized water, stir in a 30°C water bath to completely dissolve it, then add 500-700 ml of sodium hydroxide solution (2M) while maintaining stirring, and stir for 30-60 min.
[0046] (2) Slowly drop 1.5-2 ml of tetraethyl orthosilicate (TEOS) and continue stirring for 15-30 min. Then, add 300-500 ml of deionized water to the mixture and react in a 30°C water bath for 24 h to obtain a white precipitate.
[0047] (3) After centrifugation and washing, the sample was heated from room temperature to 550 °C in a muffle furnace and calcined for 6 h.
[0048] (4) Take 20-25 mg of the obtained product and mix it with 15-20 mg of tetraphenylethylene having AIE function in acetonitrile, heat it to 50-70° C., and react for 2-4 h.
[0049] (5) Collecting the solid by centrifugation, washing and drying, and obtaining AIE functionalized mesoporous silica nanoparticles.
[0050] In another specific embodiment, the present invention provides bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises, by mass percentage, 88.5% to 90.5% of polymethyl methacrylate, 0.4% to 0.6% of benzoyl peroxide and 9% to 11% of aggregation-induced emission functionalized mesoporous silica nanoparticles; the liquid component comprises, by mass percentage, 97% to 99% of methyl methacrylate monomer, 1.5% to 2.5% of N,N-dimethyl-p-toluidine and 0.5% to 1% of hydroquinone.
[0051] Some embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. In the absence of conflict, the following embodiments and features in the embodiments can be combined with each other.
[0052] Example 1
[0053] This embodiment provides a method for preparing AIE functionalized mesoporous silica nanoparticles, which specifically comprises the following steps:
[0054] (1) Using surfactant CTAB as a template, add 200 mg of CTAB into 100 ml of deionized water, stir in a 30°C water bath to completely dissolve it, then add 500 ml of sodium hydroxide solution with a concentration of 2 M while maintaining stirring, and stir for 30 min.
[0055] (2) Slowly drop 1.5 ml of TEOS and continue stirring for 15 min. Then, add 300 ml of deionized water to the mixture and react in a 30 °C water bath for 24 h to obtain a white precipitate.
[0056] (3) After centrifugation and washing, the sample was heated from room temperature to 550 °C in a muffle furnace and calcined for 6 h.
[0057] (4) Take 20 mg of the obtained product and mix it with 15 mg of tetraphenylethylene having AIE function in acetonitrile, heat it to 50°C, and react for 2 h.
[0058] (5) Collect the solid by centrifugation, wash and dry to obtain AIE functionalized mesoporous silica nanoparticles. Figure 2 shown.
[0059] Example 2
[0060] The present embodiment provides a bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises, by mass percentage, 88.5% of polymethyl methacrylate, 0.5% of benzoyl peroxide and 11% of aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1; and the liquid component comprises, by mass percentage, 98% of methyl methacrylate monomer, 1.5% of N,N-dimethyl-p-toluidine and 0.5% of hydroquinone.
[0061] The powder component and the liquid component are stirred and evenly mixed in a mass ratio of 2:1 to obtain bone cement.
[0062] Example 3
[0063] The present embodiment provides a bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises, by mass percentage, 89.5% of polymethyl methacrylate, 0.5% of benzoyl peroxide and 10% of aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1; and the liquid component comprises, by mass percentage, 98% of methyl methacrylate monomer, 1.5% of N,N-dimethyl-p-toluidine and 0.5% of hydroquinone.
[0064] The powder component and the liquid component are stirred and evenly mixed in a mass ratio of 2:1 to obtain bone cement.
[0065] Example 4
[0066] The present embodiment provides a bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises, by mass percentage, 90.5% of polymethyl methacrylate, 0.4% of benzoyl peroxide and 9.1% of aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1; and the liquid component comprises, by mass percentage, 98% of methyl methacrylate monomer, 1.5% of N,N-dimethyl-p-toluidine and 0.5% of hydroquinone.
[0067] The powder component and the liquid component are stirred and evenly mixed in a mass ratio of 2:1 to obtain bone cement.
[0068] Example 5
[0069] The present embodiment provides a bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises, by mass percentage, 88.5% of polymethyl methacrylate, 0.6% of benzoyl peroxide and 10.9% of aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1; and the liquid component comprises, by mass percentage, 97% of methyl methacrylate monomer, 2.5% of N,N-dimethyl-p-toluidine and 0.5% of hydroquinone.
[0070] The powder component and the liquid component are stirred and mixed evenly at a mass ratio of 2.1:1 to obtain bone cement.
[0071] Example 6
[0072] The present embodiment provides a bone cement with fluorescence imaging function, wherein the bone cement comprises a powder component and a liquid component, wherein the powder component comprises, by mass percentage, 88.5% of polymethyl methacrylate, 0.5% of benzoyl peroxide and 11% of aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1; and the liquid component comprises, by mass percentage, 97% of methyl methacrylate monomer, 2% of N,N-dimethyl-p-toluidine and 1% of hydroquinone.
[0073] The powder component and the liquid component are stirred and mixed evenly at a mass ratio of 2.2:1 to obtain bone cement.
[0074] Comparative Example 1
[0075] This comparative example provides a bone cement with imaging function, which is different from the bone cement provided in Example 2 only in that the aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1 are replaced with BaSO4.
[0076] Comparative Example 2
[0077] This comparative example provides a bone cement with imaging function, which is different from the bone cement provided in Example 2 only in that the aggregation-induced emission functionalized mesoporous silica nanoparticles prepared in Example 1 are replaced with ZrO2.
[0078] Experimental Example 1 Mechanical Properties Test
[0079] The mechanical properties of the bone cements obtained in the examples and comparative examples were tested according to the medical standard YY0459-2003. The results are shown in Table 1.
[0080] Table 1 Comparison of mechanical properties of bone cement provided by Examples and Comparative Examples
[0081]
[0082]
[0083] It can be seen from Table 1 that the addition of the AIE functionalized mesoporous silica nanoparticles provided in Example 1 of the present invention has substantially no effect on the mechanical properties of bone cement, and the performance meets the requirements of YY0459 and does not affect the use.
[0084] Experimental Example 2 Biocompatibility Test
[0085] According to the national standard GB / T 16886.5-2003 "Biological Evaluation of Medical Devices Part 5: In Vitro Cytotoxicity Test", the extract test was selected, and the biocompatibility of the bone cement provided in Example 2 of the present invention and that in Comparative Example 1 was compared according to the tetrazolium (MTT) colorimetric method recommended in the cytotoxicity test in GB / T14233.2-2005. The effects of the bone cement provided in Example 2 and Comparative Example 1 on cell proliferation were used as the test standard. The test results are as follows: Figure 1 shown.
[0086] Depend on Figure 1 It can be seen that the cell proliferation rate of the bone cement provided in Example 2 is in the range of 90%-100%, while the cell proliferation rate of the bone cement provided in Comparative Example 1 is in the range of 80%-90%, which proves that the bone cement provided by the present invention has better biocompatibility than the bone cement commonly used in the prior art provided in Comparative Example 1.
[0087] Experimental Example 3 Fluorescence Imaging Test
[0088] Figure 3 These are in vitro fluorescence images of Examples 1 and 2 of the present invention under 365 nm UV excitation.
[0089] Depend on Figure 3 It can be seen that the bone cement added with AIE functionalized mesoporous silica nanoparticles in Example 2 of the present invention exhibits good fluorescence imaging performance, meeting the development performance requirements in clinical use.
[0090] Therefore, the bone cement provided by the present invention has better biological properties without affecting the mechanical properties and imaging properties, and can avoid the radiation hazards caused by X-ray detection, thus meeting clinical needs.
[0091] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.
Claims
1. Application of aggregation-induced emission functionalized mesoporous nanoparticles in fluorescence imaging of bone cement for non-diagnostic purposes.
2. A method for fluorescence imaging of bone cement, characterized in that: The fluorescent imaging method comprises adding a developer into bone cement, wherein the developer comprises aggregation-induced luminescence functionalized mesoporous nanoparticles.
3. The fluorescence imaging method according to claim 2, characterized in that: The aggregation-induced emission functionalized mesoporous nanoparticles include aggregation-induced emission functionalized mesoporous silica nanoparticles.
4. A bone cement with fluorescence imaging function, characterized in that: The bone cement comprises a powder component and a liquid component, wherein the powder component comprises aggregation-induced luminescence functionalized mesoporous nanoparticles; Preferably, the aggregation-induced emission functionalized mesoporous nanoparticles include aggregation-induced emission functionalized mesoporous silica nanoparticles.
5. The bone cement according to claim 4, characterized in that The powder component also includes polymethyl methacrylate and an initiator, and the liquid component includes methyl methacrylate monomer, a promoter and an inhibitor; Preferably, the initiator comprises benzoyl peroxide; Preferably, the accelerator comprises N,N-dimethyl-p-toluidine; Preferably, the polymerization inhibitor comprises hydroquinone.
6. The bone cement according to claim 5, characterized in that The powder component comprises, by mass percentage, 88.5% to 90.5% of polymethyl methacrylate, 0.4% to 0.6% of benzoyl peroxide and 9% to 11% of aggregation-induced luminescence functionalized mesoporous silica nanoparticles; Preferably, the powder component comprises, by mass percentage, 89.5% of polymethyl methacrylate, 0.5% of benzoyl peroxide and 10% of aggregation-induced luminescence functionalized mesoporous silica nanoparticles.
7. The bone cement according to claim 5, characterized in that The liquid component comprises, by mass percentage, 97% to 98% of methyl methacrylate monomer, 1.5% to 2.5% of N,N-dimethyl-p-toluidine and 0.5% to 1% of hydroquinone; Preferably, the liquid component comprises, by mass percentage, 97.5% of methyl methacrylate monomer, 2.0% of N,N-dimethyl-p-toluidine and 0.5% of hydroquinone.
8. The bone cement according to claim 4, characterized in that The mass ratio of the powder component to the liquid component is (2-2.2):1, preferably 2:
1.
9. The bone cement according to any one of claims 4 to 8, characterized in that: The method for preparing the aggregation-induced luminescence functionalized mesoporous silica nanoparticles comprises heating the mesoporous silica nanoparticles and functional molecules having aggregation-induced luminescence in a solvent to obtain the aggregation-induced luminescence functionalized mesoporous silica nanoparticles; Preferably, the functional molecule having aggregation-induced emission comprises tetraphenylethylene; Preferably, the solvent comprises acetonitrile; Preferably, the mass ratio of the mesoporous silica nanoparticles to the functional molecules having aggregation-induced emission is (1-1.67):1; Preferably, the amount of the mesoporous silica nanoparticles is 20-25 mg, and the amount of the functional molecules having aggregation-induced luminescence is 15-20 mg; Preferably, the heating temperature is 50-70°C and the heating time is 2-4h; Preferably, the method for preparing the mesoporous silica nanoparticles comprises adding tetraethyl orthosilicate dropwise to a template agent and then heating at a constant temperature to prepare the mesoporous silica nanoparticles; Preferably, the templating agent comprises an alkaline solution of hexadecyltrimethylammonium bromide.
10. Use of the bone cement according to any one of claims 4 to 9 in the preparation of hard tissue repair products.