Mesoporous silica / titanium-based composite material and preparation method thereof

Abstract

The invention provides a mesoporous silica / titanium-based composite material and a preparation method thereof, and belongs to the technical field of medical titanium materials. According to the method, femtosecond laser scanning is conducted on the titanium-based material in the mesoporous silicon dioxide suspension, mesoporous silicon dioxide is deposited on the surface of the titanium-based material in situ in the process that the titanium-based material is ablated through femtosecond laser, and the binding force of the mesoporous silicon dioxide and the titanium-based material is improved; a mesoporous silica micro-nano structure is constructed on the surface of the titanium-based material by using femtosecond laser, so that cell adsorption is facilitated, osteoblasts are promoted to grow on the surface of the material, and the biocompatibility of the material is improved; by controlling the concentration of the mesoporous silica suspension, the deposition amount of mesoporous silica can be increased, and the drug loading capacity is improved; by limiting the parameters of the femtosecond laser, a regular micro-nano structure beneficial to cell adsorption can be constructed.

Description

Technical Field

[0001] This invention belongs to the field of medical titanium materials technology, specifically relating to a mesoporous silica / titanium-based composite material and its preparation method. Background Technology

[0002] Titanium and its alloys are widely used in bone implants due to their excellent biocompatibility and mechanical properties. However, in clinical practice, bone implants often face problems such as bacterial infection and inadequate osseointegration. Existing medical metal surface modification technologies, such as sandblasting and acid etching, and anodizing, all have certain limitations: although sandblasting and acid etching can form micron-scale structures to promote cell adsorption, their drug loading capacity is insufficient and their osseointegration is poor; anodizing technology can regulate cell differentiation at the nanoscale, but its drug loading efficiency is limited.

[0003] Mesoporous silica is an ideal drug carrier due to its high specific surface area and regular pores. Traditional mesoporous silica coating deposition methods, such as spin coating and electrodeposition, can prepare titanium-based mesoporous silica coatings that can load drugs, but the adhesion between the mesoporous silica coating and the titanium substrate is insufficient, and the coating is prone to peeling off. Summary of the Invention

[0004] The purpose of this invention is to provide a mesoporous silica / titanium-based composite material and its preparation method. The preparation method provided by this invention can firmly bond mesoporous silica to the surface of a titanium matrix.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for preparing mesoporous silica / titanium-based composite materials, comprising: A titanium-based material is placed in a mesoporous silica suspension, and then the titanium-based material is scanned using a femtosecond laser to obtain a mesoporous silica / titanium-based composite material. The mesoporous silica suspension has a mesoporous silica mass concentration of 0.1% to 5%. The parameters of the femtosecond laser include: frequency 310~620kHz, power 1~10W, scanning speed 100~500mm / s, and line spacing 10~40μm.

[0006] Preferably, the specific surface area of ​​the mesoporous silica in the mesoporous silica suspension is 200~1200 m². 2 / g.

[0007] Preferably, the diameter of the mesoporous silica particles in the mesoporous silica suspension is 50~300nm.

[0008] Preferably, the mass concentration of mesoporous silica in the mesoporous silica suspension is 0.5-4%.

[0009] Preferably, the mass concentration of mesoporous silica in the mesoporous silica suspension is 1-2%.

[0010] Preferably, the parameters of the femtosecond laser include: frequency 310~500kHz, power 2~8W, scanning speed 200~400mm / s, and line spacing 20~35μm.

[0011] Preferably, the parameters of the femtosecond laser include: frequency 310~400kHz, power 4~7W, scanning speed 250~350mm / s, and line spacing 25~30μm.

[0012] Preferably, the titanium-based material is pure titanium or a titanium alloy.

[0013] The present invention also provides a mesoporous silica / titanium-based composite material prepared by the preparation method described above, comprising a titanium matrix with a periodic stripe structure on the surface and mesoporous silica deposited on the surface of the titanium matrix.

[0014] Preferably, the width of the periodic stripe structure is 400~900nm.

[0015] This invention provides a method for preparing a mesoporous silica / titanium-based composite material, comprising: placing a titanium-based material in a mesoporous silica suspension, and then scanning the titanium-based material using a femtosecond laser to obtain the mesoporous silica / titanium-based composite material; wherein the mass concentration of the mesoporous silica in the mesoporous silica suspension is 0.1-5%; and the parameters of the femtosecond laser include: frequency 310-620 kHz, power 1-10 W, scanning speed 100-500 mm / s, and line spacing 10-40 μm. This invention involves femtosecond laser scanning of titanium-based materials in a mesoporous silica suspension. During the ablation process of the titanium-based material by the femtosecond laser, mesoporous silica is deposited in situ on the ablated surface of the titanium-based material, forming a metallurgical composite and improving the bonding force between the mesoporous silica and the titanium-based material. By controlling the concentration of the mesoporous silica suspension, the deposition amount of mesoporous silica can be increased, thereby improving drug loading capacity. Furthermore, the femtosecond laser constructs micro- and nano-structures on the surface of the titanium-based material, which is beneficial for cell adsorption, promotes osteoblast growth on the material surface, and improves the biocompatibility of the material. By limiting the parameters of the femtosecond laser, regular micro- and nano-structures that are conducive to cell adsorption can be constructed. The results of the embodiments show that the mesoporous silica / titanium-based composite material obtained by the preparation method provided by this invention achieves a coating adhesion grade of 4A and has good cell adsorption effect, and can load a large amount of bioactive substances. Attached Figure Description

[0016] Figure 1This is a SEM image of the material after femtosecond laser scanning processing, magnified 10,000 times, in Embodiment 1 of the present invention. Figure 2 This is a SEM image of the material after femtosecond laser scanning processing, magnified 20,000 times, in Embodiment 1 of the present invention. Figure 3 SEM image of the mesoporous silica / titanium-based composite material prepared in Example 1 of this invention; Figure 4 This is a SEM image of the mesoporous silica / titanium-based composite material prepared in Example 2 of the present invention; Figure 5 This is a SEM image of the mesoporous silica / titanium-based composite material prepared in Example 3 of the present invention; Figure 6 This is a SEM image of the mesoporous silica / titanium-based composite material prepared in Comparative Example 1 of this invention; Figure 7 Cell proliferation diagrams of different samples in Test Example 2 of this invention; Figure 8 The graphs show the protein powder adsorption test results of different samples in Test Example 3 of this invention. Figure 9 This is a graph showing the adsorption of antimicrobial peptides in different samples in Test Example 4 of the present invention. Figure 10 This is a graph showing the antimicrobial peptide release test of different samples in Test Example 4 of the present invention. Detailed Implementation

[0017] All raw materials used in this invention are not particularly limited in their source; they can be purchased from the market or prepared using conventional methods known to those skilled in the art.

[0018] There are no particular restrictions on the purity of any of the raw materials used in this invention, but pharmaceutical / medical grade pure raw materials are preferred.

[0019] This invention provides a method for preparing mesoporous silica / titanium-based composite materials, comprising: A titanium-based material is placed in a mesoporous silica suspension, and then the titanium-based material is scanned using a femtosecond laser to obtain a mesoporous silica / titanium-based composite material. The mesoporous silica suspension has a mesoporous silica mass concentration of 0.1% to 5%. The parameters of the femtosecond laser include: frequency 310~620kHz, power 1~10W, scanning speed 100~500mm / s, and line spacing 10~40μm.

[0020] This invention places titanium-based materials in a mesoporous silica suspension.

[0021] In this invention, the titanium-based material is preferably pure titanium or a titanium alloy; the titanium alloy is preferably pure titanium.

[0022] In one embodiment of the present invention, the titanium-based material can be pretreated before use. The pretreatment may involve mechanical polishing of the titanium-based material, followed by ultrasonic cleaning with anhydrous ethanol and deionized water in sequence; the ultrasonic cleaning time can be 15 minutes. The present invention does not impose any particular limitation on the power of the ultrasonic cleaning, as long as it can effectively clean the titanium-based material.

[0023] In this invention, the specific surface area of ​​the mesoporous silica in the mesoporous silica suspension is preferably 200~1200 m². 2 / g, more preferably 400~800m 2 / g; As one embodiment of the present invention, the specific surface area of ​​the mesoporous silica in the mesoporous silica suspension can be 300m². 2 / g、440m 2 / g、600m 2 / g、900m 2 / g or 1000m 2 / g. Mesoporous silica can be deposited on the surface of titanium-based materials under femtosecond laser irradiation and form strong bonds, thereby improving the drug loading capacity of the materials; the specific surface area of ​​mesoporous silica within the above-mentioned range is beneficial for further improving the drug loading capacity of the materials.

[0024] In this invention, the particle diameter of the mesoporous silica in the mesoporous silica suspension is preferably 50-300 nm, more preferably 100-200 nm. As one embodiment of this invention, the particle diameter of the mesoporous silica in the mesoporous silica suspension can be 80 nm, 100 nm, 120 nm, 150 nm, 180 nm, 230 nm, or 250 nm. A particle diameter within the above range is beneficial for further improving the drug loading capacity of the material.

[0025] In this invention, the mass concentration of mesoporous silica in the mesoporous silica suspension is 0.1-5%, preferably 0.5-4%, and more preferably 1-2%. As one embodiment of this invention, the mass concentration of mesoporous silica in the mesoporous silica suspension can be 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, or 5%. The mass concentration of mesoporous silica in the mesoporous silica suspension affects the deposition amount of mesoporous silica. A mass concentration within the above range can increase the deposition amount of mesoporous silica, avoiding situations where too low a concentration results in insufficient deposition, or too high a concentration affects the energy of the femtosecond laser reaching the titanium-based material, thus reducing the deposition amount.

[0026] The present invention does not impose any particular limitation on the preparation method of the mesoporous silica suspension, as long as a uniform suspension can be obtained.

[0027] In one embodiment of the present invention, the mesoporous silica in the mesoporous silica suspension can be a commercially available product.

[0028] In one embodiment of the present invention, the mesoporous silica suspension can be placed in a petri dish.

[0029] After placing the titanium-based material in a mesoporous silica suspension, the present invention uses a femtosecond laser to scan the titanium-based material to obtain a mesoporous silica / titanium-based composite material.

[0030] In this invention, the frequency of the femtosecond laser is 310~620kHz, preferably 310~500kHz, and more preferably 310~400kHz; as one embodiment of this invention, the frequency of the femtosecond laser can be 310kHz, 350kHz, 400kHz, 450kHz, 500kHz, 550kHz or 600kHz.

[0031] In this invention, the power of the femtosecond laser is 1~10W, preferably 2~8W, and more preferably 4~7W; as one embodiment of this invention, the power of the femtosecond laser can be 1W, 3W, 5W, 7W, 9W or 10W.

[0032] In this invention, the scanning speed of the femtosecond laser is 100~500mm / s, preferably 200~400mm / s, and more preferably 250~350mm / s; as one embodiment of this invention, the scanning speed of the femtosecond laser can be 100mm / s, 200mm / s, 300mm / s, 400mm / s, or 500mm / s.

[0033] In this invention, the line spacing of the femtosecond laser is 10~40μm, preferably 20~35μm, and more preferably 25~30μm. As one embodiment of this invention, the line spacing of the femtosecond laser can be 10μm, 20μm, 25μm, 30μm, 35μm, or 40μm. When the parameters of the femtosecond laser are within the above range, a periodic stripe structure can be formed on the surface of the titanium-based material, and mesoporous silica can be deposited in situ, improving the adhesion between the mesoporous silica and the titanium substrate.

[0034] In one embodiment of the present invention, after the scanning process is completed, the obtained material can be ultrasonically cleaned to obtain a mesoporous silica / titanium-based composite material. In the present invention, the ultrasonic cleaning can remove the mesoporous silica on the surface that is not composited with the titanium matrix.

[0035] This invention utilizes femtosecond laser scanning in a mesoporous silica suspension to deposit mesoporous silica in situ onto the surface of titanium-based materials during the ablation process of the femtosecond laser, thereby improving the bonding force between the mesoporous silica and the titanium-based materials. The femtosecond laser is used to construct mesoporous silica micro / nanostructures on the surface of the titanium-based materials, which facilitates cell adsorption, promotes osteoblast growth on the material surface, and improves the biocompatibility of the material. By controlling the concentration of the mesoporous silica suspension, the deposition amount of mesoporous silica can be increased, thereby enhancing drug loading capacity. By limiting the parameters of the femtosecond laser, regular micro / nanostructures that are conducive to cell adsorption can be constructed.

[0036] The present invention also provides a mesoporous silica / titanium-based composite material prepared by the preparation method described above, comprising a titanium matrix with a periodic stripe structure on the surface and mesoporous silica deposited on the surface of the titanium matrix.

[0037] In this invention, the width of the periodic stripe structure is preferably 400-900 nm. As one embodiment of this invention, the width of the periodic stripe structure fluctuates within the range of 400-900 nm.

[0038] The mesoporous silica / titanium-based composite material provided by this invention has high coating adhesion and good cell adsorption effect, and can load a large amount of bioactive substances.

[0039] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0040] Example 1 A method for preparing a mesoporous silica / titanium-based composite material, the specific steps of which are as follows: The titanium-based material (pure titanium) was mechanically polished, and then the sample was ultrasonically cleaned in anhydrous ethanol and deionized water for 15 min in sequence to obtain the pretreated titanium-based material (P-Ti). The pretreated titanium-based material (P-Ti) was placed in a mesoporous silica suspension, and then the titanium-based material was scanned using a femtosecond laser. After the scanning process was completed, the obtained material was ultrasonically cleaned to obtain a mesoporous silica / titanium-based composite material, denoted as FS-MSN-Ti. The mesoporous silica suspension has a mesoporous silica mass concentration of 1% and a specific surface area of ​​440 m². 2 / g, the particle diameter of mesoporous silica is 100nm; The parameters of the femtosecond laser are: frequency 310kHz, power 6.7W, scanning speed 100mm / s, and line spacing 40μm.

[0041] The material obtained after femtosecond laser scanning was observed using a scanning electron microscope, and the SEM images are shown below. Figure 1 and Figure 2 As shown, where Figure 1 To obtain a SEM image magnified 10,000 times, Figure 2 This is a SEM image magnified 20,000 times. From... Figure 1 and Figure 2 It can be seen that a large amount of mesoporous silica is deposited on the surface of the titanium matrix, and its deposited morphology is loose and disordered, and the periodic stripe structure constructed by the femtosecond laser is completely covered.

[0042] The final mesoporous silica / titanium-based composite material after cleaning was observed using a scanning electron microscope (SEM), and the SEM images are shown below. Figure 3 As shown, from Figure 3 As can be seen, after cleaning and removing the unfixed mesoporous silica, the periodic stripe structure constructed by the femtosecond laser is clearly visible, and a large amount of mesoporous silica is deposited on the surface of the titanium substrate.

[0043] Example 2 A method for preparing a mesoporous silica / titanium-based composite material is the same as in Example 1, except that the mass concentration of mesoporous silica in the mesoporous silica suspension is 5%.

[0044] The prepared mesoporous silica / titanium-based composite material was observed using a scanning electron microscope, and the SEM images are shown below. Figure 4 As shown. Comparison Figure 3 , Figure 4 It can be seen that as the mass concentration of mesoporous silica in the mesoporous silica suspension increases, the deposition of mesoporous silica nanoparticles decreases relatively, indicating that a higher density of the mesoporous silica solution is not necessarily better.

[0045] Example 3 A method for preparing a mesoporous silica / titanium-based composite material is the same as in Example 1, except that the mass concentration of mesoporous silica in the mesoporous silica suspension is 0.1%.

[0046] The prepared mesoporous silica / titanium-based composite material was observed using a scanning electron microscope, and the SEM images are shown below. Figure 5 As shown. Comparison Figure 3 , Figure 5 It can be seen that the mass concentration of mesoporous silica in the mesoporous silica suspension decreases, but the deposition of mesoporous silica nanoparticles is relatively reduced.

[0047] Comparative Example 1 A method for preparing a mesoporous silica / titanium-based composite material is the same as in Example 1, except that the power of the femtosecond laser is 13W.

[0048] The prepared mesoporous silica / titanium-based composite material was observed using a scanning electron microscope, and the SEM images are shown below. Figure 6 As shown. Comparison Figure 3 , Figure 6 It can be seen that the presence of relatively flat, sheet-like areas in the titanium matrix indicates that the power of the femtosecond laser was too high. The large laser energy caused sheet-like molten areas to appear in the titanium matrix, resulting in an incomplete periodic stripe structure.

[0049] Comparative Example 2 A method for preparing a titanium-based material is the same as in Example 1, except that a mesoporous silica suspension is not used. Instead, a femtosecond laser is used to directly scan the pretreated titanium-based material, and the resulting material is denoted as FS-Ti.

[0050] Test Example 1 The coating adhesion of the mesoporous silica / titanium-based composite material prepared in Example 1 was tested according to ASTM D3359 to evaluate the adhesion level of the coating, and the coating adhesion reached level 4A.

[0051] Test Example 2 Cell adhesion and proliferation experiments were conducted on the mesoporous silica / titanium-based composite material prepared in Example 1, the titanium-based material prepared in Comparative Example 2, and the titanium-based material pretreated in Example 1. Osteoblasts were seeded onto the surfaces of the three samples, and cell adhesion on various surfaces was detected after 1, 3, and 5 days. The experimental method was as follows: 1 mL of 2×10⁻⁶ mol / L silica / titanium-based composite material was added to the surface of the samples. 4 Cell suspensions of 100 cells / mL were seeded onto the surfaces of three different samples. After culturing for 1, 3, and 5 days, the surfaces were washed with PBS, and cell viability was compared using the CCK-8 assay. The results are as follows: Figure 7 As shown in the figure, * indicates statistically significant differences. Figure 7 It can be seen that the mesoporous silica / titanium-based composite material prepared in Example 1 has the best cell-promoting effect.

[0052] Test Example 3 Protein adsorption tests were performed on the mesoporous silica / titanium-based composite material prepared in Example 1, the titanium-based material prepared in Comparative Example 2, and the pretreated titanium-based material from Example 1. Protein powder was weighed and added to PBS to prepare a BSA suspension with a concentration of 2 mg / mL. The protein was evenly dispersed in the PBS using an ultrasonic cleaner. Three parallel samples were prepared for each type of sample. The samples were placed in 24-well plates, with 1 mL of protein suspension added to each well. The plates were placed in a constant-temperature shaker at 37°C for 2 hours. After 2 hours, the plates were removed and gently rinsed to remove any unadsorbed protein from the sample surface. Then, 500 μL of 5% sodium dodecyl sulfate solution was added to each well of the plate, and the plates were placed in a constant-temperature shaker at 37°C for 1 hour. The protein concentration was then measured using a BCA protein quantification kit. The test results are shown below. Figure 8 As shown in the figure, * indicates statistically significant differences. Figure 8 It can be seen that the protein adsorption on the surface of the titanium-based material treated by femtosecond laser is higher than that on the pretreated titanium-based material. This is because the femtosecond laser treatment increases the specific surface area and roughness of the titanium-based material surface, providing favorable conditions for protein adsorption. The protein adsorption on the surface of the mesoporous silica / titanium-based composite material is higher than that of the previous two groups. This is because it retains the periodic stripe micro-nano structure constructed by the femtosecond laser, and also has a large number of mesoporous silica nanoparticles to help adsorb proteins.

[0053] Test Example 4 The mesoporous silica / titanium-based composite material prepared in Example 1, the titanium-based material prepared in Comparative Example 2, and the pretreated titanium-based material in Example 1 were subjected to antimicrobial peptide adsorption tests. Antimicrobial peptide LL-37 labeled with fluorescein isothiocyanate was selected, and three groups of samples were used for antimicrobial peptide loading. The differences in antimicrobial peptide adsorption and release among different groups were compared. The experimental method was as follows: the three groups of samples were immersed in 30 μg / mL of isothiocyanate-labeled antimicrobial peptide for 16 h, and the antimicrobial peptide loading on the titanium surface was observed using a fluorescence microscope. The test results are as follows. Figure 9 As shown. From Figure 9 It can be seen that, compared with the other two groups, the mesoporous silica / titanium-based composite material has a stronger green fluorescence on its surface. This is due to the presence of a large number of mesoporous silica nanoparticles on its surface, which enhances the ability of the titanium surface to load antimicrobial peptides.

[0054] The isothiocyanate-labeled antimicrobial peptides were dissolved at different mass concentrations (0, 0.03125, 0.0625, 0.125, 0.25, 0.5, 1, 2, 4, 8 μg / mL). Fluorescence intensity was read using a fluorescence microplate reader at excitation / emission wavelengths of 490 / 520 nm, and a standard curve was constructed. The release of antimicrobial peptides from the sample surface was calculated based on the curve. The results are as follows: Figure 10 As shown. From Figure 10It can be seen that the surface of the mesoporous silica / titanium-based composite material continuously releases antimicrobial peptides within 14 days, and the number of released peptides is higher than that of femtosecond laser-treated titanium-based materials and pretreated titanium-based materials.

[0055] As can be seen from the above embodiments, the mesoporous silica / titanium-based composite material coating prepared by the method of the present invention has good adhesion and good cell adsorption effect, and can load more bioactive substances.

[0056] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a mesoporous silica / titanium-based composite material, comprising: A titanium-based material is placed in a mesoporous silica suspension, and then the titanium-based material is scanned using a femtosecond laser to obtain a mesoporous silica / titanium-based composite material. The mesoporous silica suspension has a mesoporous silica mass concentration of 0.1% to 5%. The parameters of the femtosecond laser include: frequency 310~620kHz, power 1~10W, scanning speed 100~500mm / s, and line spacing 10~40μm.

2. The preparation method according to claim 1, characterized in that, The specific surface area of ​​the mesoporous silica in the mesoporous silica suspension is 200~1200 m². 2 / g.

3. The preparation method according to claim 1, characterized in that, The mesoporous silica suspension contains mesoporous silica particles with a diameter of 50~300nm.

4. The preparation method according to any one of claims 1 to 3, characterized in that, The mesoporous silica suspension has a mesoporous silica mass concentration of 0.5-4%.

5. The preparation method according to claim 4, characterized in that, The mass concentration of mesoporous silica in the mesoporous silica suspension is 1-2%.

6. The preparation method according to claim 1, characterized in that, The parameters of the femtosecond laser include: frequency 310~500kHz, power 2~8W, scanning speed 200~400mm / s, and line spacing 20~35μm.

7. The preparation method according to claim 6, characterized in that, The parameters of the femtosecond laser include: frequency 310~400kHz, power 4~7W, scanning speed 250~350mm / s, and line spacing 25~30μm.

8. The preparation method according to claim 1, characterized in that, The titanium-based material is pure titanium or a titanium alloy.

9. The mesoporous silica / titanium-based composite material prepared by the preparation method according to any one of claims 1 to 8 comprises a titanium matrix with a periodic stripe structure on its surface and mesoporous silica deposited on the surface of the titanium matrix.

10. The mesoporous silica / titanium-based composite material according to claim 9, characterized in that, The width of the periodic stripe structure is 400~900nm.

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