Preparation method and application of a poly-citric acid-based adhesive composite coating

Abstract

This invention discloses a method for preparing a polycitric acid-based adhesive composite coating. The method includes the following steps: Step 1: After melting citric acid, polyethylene glycol and 1,8-octanediol are added, acrylic acid is added dropwise and stirred, and the mixture is dissolved, purified by dialysis, and then freeze-dried under vacuum to obtain a double-bonded polycitric acid ester prepolymer; Step 2: Polylysine is mixed with the double-bonded polycitric acid ester prepolymer to obtain a polycitric acid ester composite solution; Step 3: The polycitric acid ester composite solution is dropwise added to the surface of a substrate and thermosetting to obtain a polycitric acid-based adhesive composite coating. This invention also discloses the applications of the polycitric acid-based adhesive composite coating. This invention, by adding acrylic acid to the polycitric acid prepolymer system to generate a double-bonded polycitric acid ester prepolymer, and by adding polylysine to form a polycitric acid ester composite solution, forms a polycitric acid-based adhesive composite coating with strong adhesion after thermosetting, which is applicable to the field of biodegradable biomedical materials technology.

Description

Technical Field

[0001] This invention belongs to the field of biodegradable biomedical materials technology, and in particular relates to a method for preparing and applying a polycitric acid-based adhesive composite coating. Background Technology

[0002] In recent years, zinc (Zn) and its alloys have become increasingly popular biodegradable metals following magnesium and iron-based metals due to their excellent corrosion resistance and mechanical properties, and are now being applied in the field of bone repair. However, compared with years of research and application in the industrial field, research on Zn-based biodegradable metals in the biological field is still in its early stages. Especially for complex bone defect environments, single-function Zn metals cannot achieve satisfactory therapeutic effects. Therefore, researching how to improve the multifunctional properties of Zn metals to effectively address complex bone defect environments is particularly important.

[0003] Currently, efforts to improve the multifunctional properties of Zn metal mainly focus on constructing coatings with appropriate corrosion behavior and good biocompatibility on the Zn metal surface. For example, constructing a phosphate conversion membrane on the Zn metal surface can improve the viability, adhesion, and proliferation of pre-osteoblastic cells while inhibiting the adhesion of E. coli. Similarly, preparing a calcium phosphate-rich protective film on the Zn-1.5Mg alloy surface can improve the viability and adhesion of U-2OS cells. Furthermore, a dexamethasone-loaded ZnO nanotube composite coating was prepared on a Zn metal substrate via anodic oxidation and silk fibroin / graphene self-assembly. This composite coating enhances biocompatibility and antibacterial properties due to the synergistic release of Zn ions and the drug during degradation. However, the adhesion between these coatings and the substrate is relatively low, leading to easy detachment during practical use. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for preparing a polycitric acid-based adhesive composite coating. This method involves adding acrylic acid to a reaction system for preparing a polycitric acid prepolymer to generate a double-bonded polycitric acid ester prepolymer. This prepolymer then reacts with polylysine to form a polycitric acid ester composite solution, which is subsequently thermocured to form a polycitric acid-based adhesive composite coating. This coating exhibits strong adhesion to the substrate, solving the problem of low adhesion between the coating and the substrate in existing technologies, leading to easy detachment during practical use.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is: a method for preparing a polycitric acid-based adhesive composite coating, characterized in that the preparation method includes the following steps:

[0006] Step 1: After melting citric acid under nitrogen protection, polyethylene glycol and 1,8-octanediol are added, followed by the addition of acrylic acid and stirring under vacuum. The mixture is then dissolved, purified by dialysis, and freeze-dried under vacuum to obtain a double-bonded polycitric acid ester prepolymer.

[0007] Step 2: Mix polylysine with the double-bonded polycitrate prepolymer obtained in Step 1 to obtain a polycitrate composite solution;

[0008] Step 3: The polycitric acid ester composite solution obtained in Step 2 is dropped onto the substrate surface and spread. After thermosetting, a polycitric acid ester-based adhesive composite coating is obtained.

[0009] The present invention improves the antibacterial ability of polycitric acid-based adhesive composite coating by adding polylysine. At the same time, polylysine has binding sites, which can improve the adhesion of polycitric acid-based adhesive composite coating to substrate and cells.

[0010] The method for preparing a polycitric acid-based adhesive composite coating is characterized in that the melting temperature in step one is 160°C and the temperature during the addition of acrylic acid is 130°C.

[0011] This invention adjusts the temperature to 130°C to prevent the reaction system from solidifying when the temperature is below 130°C and to prevent a large amount of acrylic acid from volatilizing when the temperature is above 130°C.

[0012] The method for preparing a polycitric acid-based adhesive composite coating is characterized in that the molar ratio of citric acid to acrylic acid in step one is 1:1.

[0013] The method for preparing a polycitric acid-based adhesive composite coating is characterized in that, in step two, the concentration of polylysine in the polycitric acid composite solution is 1 mg / mL to 2 mg / mL, and the mass concentration of the double-bonded polycitric acid prepolymer in the polycitric acid composite solution is 1% to 15%.

[0014] This invention controls the concentration of polylysine and double-bonded polycitrate prepolymer in the polycitrate composite solution to avoid cytotoxicity caused by excessively high concentrations and to avoid weakening the biological function of the polycitrate-based adhesive composite coating by excessively low concentrations.

[0015] The method for preparing a polycitric acid-based adhesive composite coating is characterized in that bioactive glass nanoparticles are added to the polycitric acid ester composite solution in step two.

[0016] This invention enhances the bioactivity of polycitrate-based adhesive composite coatings by adding bioactive glass nanoparticles to a polycitrate composite solution.

[0017] The method for preparing a polycitric acid-based adhesive composite coating is characterized in that the concentration of the bioactive glass nanoparticles in the polycitric acid composite solution is 1 mg / mL to 2 mg / mL.

[0018] The method for preparing a polycitric acid-based adhesive composite coating described above is characterized in that the amount of polycitric acid ester composite solution added in step three is 10 μL to 100 μL.

[0019] The method for preparing a polycitric acid-based adhesive composite coating is characterized in that the thermosetting temperature in step three is 50℃~80℃ and the thermosetting time is 2h~5h.

[0020] In addition, the present invention also discloses the use of the above-mentioned polycitric acid-based adhesive composite coating, characterized in that the polycitric acid-based adhesive composite coating is used for bone repair.

[0021] Compared with the prior art, the present invention has the following advantages:

[0022] 1. This invention generates a double-bonded polycitric acid ester prepolymer with excellent reactivity and functionality by adding acrylic acid to the reaction system for preparing polycitric acid prepolymer. This introduces more crosslinking points and functional groups, which is beneficial to improving the adhesion between the polycitric acid-based adhesive composite coating and the substrate, thus making it less likely to fall off during use. At the same time, the polycitric acid-based adhesive composite coating can provide an acidic environment to accelerate the decomposition of the Zn matrix and increase the release rate of Zn ions.

[0023] 2. The polycitric acid-based adhesive composite coating prepared by the present invention can still have strong adhesion when the thickness of the polycitric acid-based adhesive composite coating reaches more than 60μm, and can be firmly bonded to the Zn matrix.

[0024] 3. This invention uses citric acid, acrylic acid, and polylysine as raw materials to prepare a polycitric acid-based adhesive composite coating, which can greatly reduce production costs. Moreover, the preparation process is simple and can be completed without complex equipment or harsh conditions, effectively reducing the difficulty of technology promotion and industrial production.

[0025] 4. This invention, by precisely controlling the composition and concentration of each component in the polycitric acid ester composite solution, can control the function and thickness of the polycitric acid-based adhesive composite coating. This polycitric acid-based adhesive composite coating has a large number of active sites, which can attach multiple components to the substrate surface, thus preparing a polycitric acid-based adhesive composite coating with adjustable composition and controllable performance. This polycitric acid-based adhesive composite coating has a high degree of customization capability, and can be precisely designed according to different biomedical needs, opening up broad space for the application of Zn metal in diverse medical scenarios.

[0026] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0027] Figure 1 The graph shows the osteogenic performance test results of the polycitric acid-based adhesive composite coating, Zn, and blank group prepared in Example 1 of this invention.

[0028] Figure 2 This is a microscopic morphology diagram of Zn in Embodiment 1 of the present invention.

[0029] Figure 3 This is a microscopic morphology diagram of the polycitric acid-based adhesive composite coating prepared in Example 1 of the present invention.

[0030] Figure 4 This is a microscopic morphology diagram of the polycitric acid-based adhesive composite coating obtained in Example 2 of the present invention.

[0031] Figure 5 This is a microscopic morphology image of the side surface of the polycitric acid-based adhesive composite coating prepared in Example 1 of the present invention.

[0032] Figure 6 This is a microscopic morphology image of the side surface of the polycitric acid-based adhesive composite coating prepared in Example 2 of the present invention.

[0033] Figure 7 This is a graph showing the relationship between acoustic signal, friction force, and displacement of the polycitric acid-based adhesive composite coating prepared in Example 1 of the present invention.

[0034] Figure 8 This is a graph showing the relationship between the acoustic signal and probe pressure of the polycitric acid-based adhesive composite coating prepared in Example 1 of the present invention.

[0035] Figure 9 This is a graph showing the relationship between acoustic signal, friction force, and displacement of the polycitric acid-based adhesive composite coating prepared in Example 2 of the present invention.

[0036] Figure 10 This is a graph showing the relationship between the acoustic signal and probe pressure of the polycitric acid-based adhesive composite coating prepared in Example 2 of the present invention.

[0037] Figure 11 The figures show the results of hydrophilic experiments on the polycitric acid-based adhesive composite coatings and Zn prepared in Examples 1 and 2 of this invention.

[0038] Figure 12 The graph shows the 1-day cell compatibility test results of the polycitric acid-based adhesive composite coating, Zn, and blank group prepared in Examples 1 and 2 of this invention.

[0039] Figure 13The graph shows the 3-day cell compatibility test results of the polycitric acid-based adhesive composite coating, Zn, and blank group prepared in Examples 1 and 2 of this invention.

[0040] Figure 14 The graph shows the detection results of Zn ion release of the polycitric acid-based adhesive composite coating and Zn obtained in Examples 1 and 2 of this invention. Detailed Implementation

[0041] Example 1

[0042] This embodiment includes the following steps:

[0043] Step 1: Melt 4g of citric acid at 160℃ for 10min under nitrogen protection, then add 6.25g of polyethylene glycol and 1,8-octanediol. Lower the temperature to 130℃ and add 1.5g of acrylic acid dropwise. Stir vigorously under vacuum for 5h, then sequentially dissolve, dialyze, purify, and freeze-dry under vacuum to obtain double-bonded polycitric acid ester prepolymer; the dialyze purification time is 3 days.

[0044] Step 2: Mix polylysine with the double-bonded polycitrate prepolymer obtained in Step 1, and then add bioactive glass nanoparticles to obtain a polycitrate composite solution; the concentration of polylysine in the polycitrate composite solution is 1 mg / mL, the concentration of bioactive glass nanoparticles in the polycitrate composite solution is 1 mg / mL, the mass concentration of the double-bonded polycitrate prepolymer in the polycitrate composite solution is 1%, and the bioactive glass nanoparticles are Cu ion-doped bioactive glass nanoparticles;

[0045] Step 3: Drop 100 μL of polycitric acid ester composite solution obtained in Step 2 onto the Zn surface and spread it. Heat cure it at 50°C for 3 hours to obtain a polycitric acid-based adhesive composite coating.

[0046] The polycitric acid-based adhesive composite coating obtained in this embodiment is denoted as Zn@P1.

[0047] Osteogenic properties of uncoated Zn and Zn@P1 were assessed using MC3T3-E1 osteoblasts. Extracts of uncoated Zn and Zn@P1 were prepared according to the relevant provisions of ISO 10993, "Biocompatibility Testing". The extracts of uncoated Zn and Zn@P1 were diluted 25-fold and co-cultured with MC3T3-E1 osteoblasts for 28 days. Results of calcium deposition (CAL) and collagen secretion (COL) are as follows: Figure 1As shown, compared with Ctrl (representing co-culture with MC3T3-E1 osteoblasts under blank cell culture plate conditions), the calcium deposition of both Zn and Zn@P1 was increased, with Zn@P1 showing shorter error bars and more uniform calcium deposition. Compared with Ctrl and Zn, Zn@P1 exhibited a higher collagen secretion value. In summary, this indicates that the polycitric acid-based adhesive composite coating prepared in this embodiment has a good osteopromoting effect.

[0048] Example 2

[0049] The difference between this embodiment and Embodiment 1 is that the mass concentration of the double-bonded polycitric acid ester prepolymer in the polycitric acid ester composite solution in step two is 5%.

[0050] The polycitric acid-based adhesive composite coating obtained in this embodiment is denoted as Zn@P5.

[0051] Morphological characterization was performed on uncoated Zn, Zn@P1, and Zn@P5, and the surface morphology characteristics are as follows: Figures 2 to 4 As shown, obvious scratches were observed on the Zn surface, and a large number of bioactive glass nanoparticle aggregates were observed on the Zn@P1 surface. The Zn@P5 surface was smoother than Zn@P1, and both Zn@P1 and Zn@P5 were able to adhere uniformly to the Zn surface. The side morphology of Zn@P1 and Zn@P5 was also characterized, as shown below. Figure 5 and Figure 6 As shown, the thickness of Zn@P1 was measured to be 25.70 μm and the thickness of Zn@P5 was 66.99 μm, indicating that the preparation method of the present invention can adjust the thickness of the polycitric acid-based adhesive composite coating by adjusting the concentration of the double-bonded polycitric acid ester prepolymer.

[0052] The adhesion of Zn@P1 and Zn@P5 coatings was tested using a nano-scratch tester, and the results are as follows: Figures 7 to 10 As shown, the critical adhesion force (Fc) of the coating was determined based on the abrupt change point of the acoustic signal and friction force. The adhesion force of the Zn@P1 coating was 5004.56 mN and the adhesion force of the Zn@P5 coating was 4115.36 mN, indicating that the polycitric acid-based adhesive composite coating has strong adhesion to the Zn surface.

[0053] Hydrophilicity experiments were conducted on Zn@P1 and Zn@P5 using a water contact angle meter, and the results are as follows: Figure 11 As shown, compared with Zn, both Zn@P1 and Zn@P5 have good hydrophilicity, and the surface water contact angle of Zn@P1 and Zn@P5 decreases continuously with time.

[0054] Cell compatibility was assessed using MC3T3-E1 osteoblasts. Following the guidelines in ISO 10993, uncoated Zn, Zn@P1, and Zn@P5 extracts were prepared and diluted 25-fold and 50-fold (denoted as x25 and x50, respectively). These diluted extracts were then co-cultured with MC3T3-E1 osteoblasts for 1 day and 3 days, respectively. The results are as follows: Figure 12 and Figure 13 As shown (Ctrl indicates co-culture with MC3T3-E1 osteoblasts under blank cell culture plate conditions), the extracts of each group showed good cell activity after co-culturing with MC3T3-E1 osteoblasts for 1 day and 3 days, indicating that the polycitrate adhesive composite coating has good compatibility with osteoblasts.

[0055] Uncoated Zn, Zn@P1, and Zn@P5 were immersed in DMEM cell culture medium for 24 hours, and the Zn ion release was tested. The results are as follows: Figure 14 As shown, compared with uncoated Zn, the Zn ion release in the immersion solution of Zn@P1 and Zn@P5 is higher, both exceeding 370 mg / L, indicating that the polycitric acid-based adhesive composite coating can significantly increase the release of Zn ions.

[0056] Example 3

[0057] The difference between this embodiment and Example 1 is that: in step two, the concentration of polylysine in the polycitrate composite solution is 2 mg / mL, the concentration of bioactive glass nanoparticles in the polycitrate composite solution is 2 mg / mL, and the mass concentration of double-bonded polycitrate prepolymer in the polycitrate composite solution is 15%; in step three, 90 μL of polycitrate composite solution is dropped onto the Zn surface and spread, and then thermo-cured at 60°C for 5 h.

[0058] The citric acid-based adhesive composite coating obtained in this embodiment was tested and found to have a thickness of 200.01 μm and an adhesion of 4500.00 mN.

[0059] Example 4

[0060] The difference between this embodiment and embodiment 3 is that in step 3, 10 μL of polycitric acid ester composite solution is dropped onto the Zn surface and spread, and then heat-cured at 80°C for 2 hours.

[0061] The citric acid-based adhesive composite coating obtained in this embodiment has a thickness of 46.12 μm and an adhesion strength of 4710.21 mN.

[0062] The above description is merely a preferred embodiment of the present invention and does not constitute any limitation on the present invention. Any simple modifications, alterations, or equivalent structural transformations made to the above embodiments based on the technical essence of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A method for preparing a polycitric acid-based adhesive composite coating that can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, characterized in that, The preparation method includes the following steps: Step 1: After melting citric acid under nitrogen protection, polyethylene glycol and 1,8-octanediol are added, followed by the addition of acrylic acid and stirring under vacuum. The mixture is then dissolved, purified by dialysis, and freeze-dried under vacuum to obtain a double-bonded polycitric acid ester prepolymer. Step 2: Mix polylysine with the double-bonded polycitrate prepolymer obtained in Step 1 to obtain a polycitrate composite solution; add bioactive glass nanoparticles to the polycitrate composite solution; the concentration of polylysine in the polycitrate composite solution is 1 mg / mL to 2 mg / mL, and the mass concentration of the double-bonded polycitrate prepolymer in the polycitrate composite solution is 1% to 15%; Step 3: The polycitric acid ester composite solution obtained in Step 2 is dropped onto the Zn matrix surface and spread. After thermosetting, a polycitric acid ester adhesive composite coating is obtained.

2. The method for preparing a polycitric acid-based adhesive composite coating according to claim 1, which can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, is characterized in that... The melting temperature in step one is 160°C, and the temperature during the addition of acrylic acid is 130°C.

3. The method for preparing a polycitric acid-based adhesive composite coating according to claim 1, which can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, is characterized in that... The molar ratio of citric acid to acrylic acid in step one is 1:

1.

4. The method for preparing a polycitric acid-based adhesive composite coating according to claim 1, which can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, is characterized in that... The concentration of the bioactive glass nanoparticles in the polycitrate composite solution is 1 mg / mL to 2 mg / mL.

5. The method for preparing a polycitric acid-based adhesive composite coating according to claim 1, which can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, is characterized in that... The amount of polycitric acid ester composite solution added in step three is 10 μL to 100 μL.

6. The method for preparing a polycitric acid-based adhesive composite coating according to claim 1, which can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, is characterized in that... The thermosetting temperature in step three is 50℃~80℃, and the thermosetting time is 2h~5h.

7. The use of a polycitric acid-based adhesive composite coating prepared according to any one of claims 1 to 6, which can accelerate the decomposition of Zn matrix and increase the release rate of Zn ions, characterized in that, The polycitric acid-based adhesive composite coating is used for bone repair.

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