A bimetallic MOF hydrogel dressing for promoting wound healing and its preparation method and application

Abstract

This application provides a bimetallic MOF hydrogel dressing that promotes wound healing, its preparation method, and its application, relating to the field of antibacterial materials technology. The bimetallic MOF hydrogel dressing is composed of a bimetallic organometallic framework loaded onto a multifunctional hydrogel. This bimetallic MOF hydrogel dressing possesses multiple functions, simultaneously exhibiting excellent antibacterial properties, healing-promoting functions, and biocompatibility, and has broad application prospects in biomedicine.

Description

Technical Field

[0001] This application relates to the field of antibacterial materials technology, specifically to a bimetallic MOF hydrogel dressing that promotes wound healing, its preparation method, and its application. Background Technology

[0002] Wound healing is generally considered a dynamic process, and an ideal wound dressing should maintain a suitable moist environment, have the ability to absorb wound exudate and prevent microbial invasion, and also possess some gas exchange capabilities. This can significantly promote wound healing. Traditional wound dressings, such as sterile gauze, sterile absorbent cotton, and bandages, can provide a simple physical protective barrier for the wound, but their absorption and drainage effects on wound exudate are limited, easily leading to wound infection, and are not conducive to maintaining a moist healing environment. The use of anti-infective wound dressings has become the main method to promote wound healing.

[0003] In recent years, hydrogel wound dressings have been extensively studied. Hydrogels possess suitable porosity and good breathability, and they can maintain a moist environment around the wound, effectively promoting wound healing. Hydrogels also exhibit good mechanical strength, making them suitable for joint wounds and as a dressing substrate. However, although hydrogel wound dressings have good biocompatibility, their antibacterial properties do not meet expectations. Summary of the Invention

[0004] The inventors discovered that natural biomaterials possess biodegradability and good compatibility. Good biomaterials include collagen, starch, and chitosan (CS). Among these, CS exhibits excellent adhesion, hemostasis, and antibacterial properties in biomedicine, making it one of the most promising wound dressing materials. By adding modifying materials, the performance of CS can be expanded, giving it antibacterial, hemostatic, and biocompatible functions.

[0005] Metal-organic frameworks (MOFs) are a novel type of inorganic hybrid polymer. Their porous and regular structural properties make them promising for applications in biomedicine and drug delivery. Compared to traditional bactericides, MOF antibacterial agents offer advantages such as broad-spectrum antibacterial activity, high efficacy, long duration of action, tunable structure, and good thermal stability. However, MOF structures have relatively poor biocompatibility. The antibacterial mechanisms of MOFs include two aspects: one is the interaction between active sites on the MOF surface and the bacterial surface, achieving bactericidal effects; the other is the disruption of bacterial cell membrane permeability by metal ions leached from the MOF crystals, thus achieving a bactericidal effect. The numerous three-dimensional structures and large surface area of ​​MOFs provide many metal active sites, enhancing their lipophilicity and enabling lipid peroxidation in bacterial cell membranes, leading to cell membrane damage and exhibiting excellent antibacterial properties.

[0006] Through extensive research, the inventors discovered that wound healing requires the promotion of angiogenesis, collagen deposition, and re-epithelialization. Copper-containing materials possess angiogenesis-promoting and antibacterial properties, and transition metal nanoparticles, particularly silver nanoparticles, have a significant impact on multidrug-resistant bacteria. However, excessive leaching of metal ions from metal nanoparticles is harmful to normal cells in the human body and may lead to cell damage, hindering effective sustained-release sterilization. Combining metal ions with MOFs allows for the slow release of metal ions within the physiological environment, selectively targeting bioactive Ag. + and Cu 2+ Using metal nodes as MOF structures to prepare bimetallic organometallic frameworks (bMOFs) allows for the uniform dispersion of metal ions in polymer matrices due to their unique rod-like structure. This enables the continuous release of metal ions, resulting in long-lasting bactericidal properties and high stability, thus achieving the purpose of slow-release sterilization.

[0007] To address the aforementioned issues, the first aspect of this application provides a bimetallic MOF hydrogel dressing that promotes wound healing. The bimetallic MOF hydrogel dressing (PCbM) is composed of a bimetallic organometallic framework loaded onto a multifunctional hydrogel.

[0008] A second aspect of this application provides a method for preparing a bimetallic MOF hydrogel dressing, the method comprising the following steps:

[0009] S1: The bimetal is mixed with a ligand and heated to obtain a bimetallic organometallic framework.

[0010] S2: Add the bimetallic organometallic framework to the PVA solution, mix and heat.

[0011] S3: Add chitosan solution to step S2 and heat to obtain a viscous sample solution.

[0012] S4: The viscous sample solution is subjected to cyclic freezing and thawing to obtain a bimetallic MOF hydrogel dressing.

[0013] In step S1, the heating temperature is 100-120℃.

[0014] The heating temperature in step S2 is 80-100℃.

[0015] The heating temperature in step S3 is 45-60℃.

[0016] The third aspect of this application provides the application of a bimetallic MOF hydrogel dressing in antibacterial materials.

[0017] Compared with the prior art, this application achieves at least one of the following beneficial effects:

[0018] (1) The bimetallic MOF hydrogel dressing of this application possesses excellent antibacterial properties, water retention, swelling properties, water vapor permeability, and biocompatibility. The sustained-release characteristics of MOF are closely related to its structure, with low concentrations of exudated metal ions, reducing toxicity to the human body. Due to the special structure of MOF, it exhibits excellent antibacterial properties. The antibacterial dressing isolates external bacteria from contact with the wound surface, destroying the physiological structure of bacteria in a short time. The synergistic effect of metal ions and hydrogel can promote platelet and erythrocyte aggregation and exhibit tissue adhesion, which can be used for rapid hemostasis of wounds. Dressings with a certain ion release amount exhibit better erythrocyte compatibility and can reduce the destructive effect on erythrocytes.

[0019] (2) The bimetallic MOF hydrogel dressing of this application has multiple functions, and can simultaneously have excellent antibacterial properties, healing promotion function and biocompatibility, and has broad application prospects in biomedicine.

[0020] (3) In the bimetallic MOF hydrogel dressing of this application, PVA and CS are selected as hydrogel materials, which have good tissue adhesion and hemostatic ability, can significantly promote wound healing, and have good biocompatibility.

[0021] (4) This application selects bioactive Ag + and Cu 2+ Using metal nodes as MOF structures to fabricate bMOFs, due to their special rod-like structure, not only can they be uniformly dispersed in the polymer matrix, but they can also continuously release metal ions, giving them the characteristics of long-lasting bactericidal performance and high stability, thereby achieving the purpose of slow-release sterilization. Furthermore, they can avoid direct contact with wounds, thus avoiding hemolysis and cell death, and have excellent mechanical properties, resistance to bacterial penetration, and can reduce the amount of metal ions that penetrate the skin.

[0022] (5) The presence of bMOF in the bimetallic MOF hydrogel dressing of this application reduces the crosslinking density of CS in the hydrogel dressing, giving the hydrogel good water retention. It can absorb tissue fluid from the wound and drain it quickly, preventing wound fluid retention and creating a moist environment for the wound. The final PCbM wound dressing has the characteristics of good biocompatibility, low hemolysis rate, and low cytotoxicity, providing ideas for the research of novel wound dressings. Attached Figure Description

[0023] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments of this application and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings:

[0024] Figure 1 The diagram shows a comparison of the antibacterial properties of Example 1 of this application and Comparative Examples 2-4;

[0025] Figure 2 A comparison diagram of cell viability between Example 1 of this application and Comparative Examples 2-4 is shown;

[0026] Figure 3 The comparison graphs of water vapor transmission rate and water retention of Example 1 and Comparative Examples 2-4 are shown.

[0027] Figure 4 The figure shows a test diagram of the hemostatic performance of the PCbM dressing of this application after tail amputation in mice according to Example 1 of this application;

[0028] Figure 5 A comparative diagram showing the hemostatic performance of the PCbM dressing of this application applied to mice after tail amputation in Example 1 of this application is shown.

[0029] Figure 6 The following is a test diagram showing the hemostatic performance of the PCbM dressing of this application applied to a mouse liver wound in Example 1 of this application;

[0030] Figure 7 A comparative diagram showing the wound-healing effect in mice according to Example 1 of this application is shown;

[0031] Figure 8 The diagram shows a test image of the wound area in a mouse according to Example 1 of this application;

[0032] Figure 9 The PCbM EDS spectrum of this application is shown. Detailed Implementation

[0033] To more clearly illustrate the overall concept of this application, a detailed explanation is provided below with reference to the accompanying drawings.

[0034] Many specific details are set forth in the following description in order to provide a full understanding of this application. However, this application may also be implemented in other ways different from those described herein. Therefore, the scope of protection of this application is not limited to the specific embodiments disclosed below.

[0035] Furthermore, it should be understood in the description of this application that the terms "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0036] In this application, unless otherwise expressly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection, an electrical connection, or a communication connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0037] In this application, unless otherwise expressly specified and limited, the "above" or "below" of the second feature can mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. In the description of this specification, references to terms such as "an embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described can be combined in any suitable manner in one or more embodiments or examples.

[0038] In one exemplary embodiment of this application, the bimetallic MOF hydrogel dressing is composed of a bimetallic organometallic framework loaded on a multifunctional hydrogel.

[0039] Optionally, the bimetallic organometallic framework can use 3,5-pyridinedicarboxylic acid (H2PYDC) as a ligand.

[0040] Optionally, the bimetallic organometallic framework contains Ag. + Cu 2+ Fe 3+ Zn 2+ Any two of the following. Preferably, the bimetallic organometallic framework contains Ag. + and Cu 2+ .

[0041] Optionally, the multifunctional hydrogel may be one or more of collagen, starch, CS, and PVA. Preferably, the multifunctional hydrogel is composed of PVA and chitosan.

[0042] Specifically, the preparation method of bimetallic MOF hydrogel dressing includes the following steps:

[0043] S1: The bimetal is mixed with a ligand and heated to obtain a bimetallic organometallic framework;

[0044] S2: Add the bimetallic organometallic framework to the PVA solution, mix, and heat;

[0045] S3: Add CS solution to step S2 and heat to obtain a viscous sample solution;

[0046] S4: The viscous sample solution is subjected to cyclic freezing and thawing to obtain a bimetallic MOF hydrogel dressing;

[0047] In step S1, the heating temperature is 100-120℃. If the temperature in step S1 is too low, the bMOF crystal cannot be formed through self-assembly. If the temperature in step S1 is too high, the pressure inside the reactor will increase, which will affect the safety of the experiment.

[0048] The heating temperature in step S2 is 80-100℃; if the temperature is too low in step S2, it will affect the solubility of PVA, and if the temperature is too high, it will cause the solution to boil, affecting the safety of the experiment.

[0049] The heating temperature in step S3 is 45-60℃. If the temperature in step S3 is too low, it will affect the dissolution and dispersion of CS; if the temperature is too high, it will cause CS to denature.

[0050] Optionally, the heating temperature in step S1 is 110-117℃;

[0051] And / or the heating temperature in step S2 is 85-95℃;

[0052] And / or the heating temperature in step S3 is 50-55℃.

[0053] Preferably, the heating temperature in step S1 is 120°C;

[0054] And / or the heating temperature in step S2 is 100°C;

[0055] The heating temperature in step S3 is 45°C.

[0056] Optionally, in step S1, the bimetallic compounds are silver ions and copper ions, and the mass ratio of silver ions:copper ions:ligand is 0.17–0.96:0.18–0.57:0.14. Preferably, the ratio of silver ions:copper ions:ligand is 0.3–0.5:0.4–0.55:0.14.

[0057] By mass ratio, bMOF:PVA:CS is 0.1–2%: 5–10%: 1–2%.

[0058] Specifically, during the synthesis of bMOF, if the content of a certain metal ion is too high, the assembly of MOF crystals will tend to generate MOF structures with a large number of single metal ions, affecting the synthesis rate of bMOF. In bimetallic MOF hydrogel dressings, if the content of bMOF is too high, the metal ion content in the dressing will be too high, affecting the safety of the dressing. If the hydrogel content is too high, it will affect the dressing's molding; if the hydrogel content is too low, the dressing will be too hard and not easy to adhere to the wound. In addition, the addition of MOF materials can reduce the adhesion density of the hydrogel, increase the porosity, and improve the swelling rate of the hydrogel, giving the prepared PCbM dressing better water absorption, thereby improving the dressing's hemostatic and healing-promoting functions.

[0059] Specifically, the preparation method of the bimetallic MOF hydrogel dressing includes the following steps:

[0060] S1: Preparation of bMOF: Dissolve 0.1-0.55g AgNO3, 0.1-0.6g Cu(NO3)2·3H2O and 0.1-0.3g H2PYDC in deionized water and mix thoroughly. Seal the mixture in an autoclave and heat it at 100-120℃. Then centrifuge at 4800-5000rpm for 10-15min. After precipitation, discard the supernatant, wash the precipitate and dry it at 50℃-60℃ to obtain bMOF.

[0061] S2: PVA is dissolved by heating at 80-100℃ to obtain a PVA solution. bMOF is added to the PVA solution under nitrogen protection to make the bMOF content in the solution 1-1.2 mg / g.

[0062] S3: Dissolve 0.2-0.3g of chitosan in 10-20ml of water, then add it to step S2, and add 5-15ml of acetic acid solution to obtain a viscous sample solution;

[0063] S4: The prepared viscous sample solution is cast onto a plastic mold, vacuum treated, and then the mold is frozen at -20℃ to -15℃ and thawed at 20-30℃. This process is repeated for 4-5 cycles to obtain PCbM.

[0064] refer to Figure 9 The EDS spectrum is shown below. Figure 9 The upper left image shows the structure of PCbM, the upper right image shows the distribution of C in PCbM, the lower left image shows the distribution of Ag in PCbM, and the lower right image shows the distribution of Cu in PCbM. It can be seen that PCbM is indeed loaded with Ag and Cu ions.

[0065] Example 1

[0066] The preparation method of bimetallic MOF hydrogel dressing includes the following steps:

[0067] Preparation of bMOF (S1): Dissolve 0.34g AgNO3 and 0.374g Cu(NO3)2·3H2O in 10-15ml deionized water. Disperse 0.14g H2PYDC in 8-15ml deionized water by ultrasonication. Mix the two solutions together and seal them in a steel autoclave. Heat at 120℃ for 24h, then centrifuge at 5000rpm for 10min. After precipitation, discard the supernatant. Wash the precipitate three times and dry it at 50℃ for 4h to obtain bMOF. The content of Ag ions in bMOF is 2mmol and the content of Cu ions is 2mmol.

[0068] Synthetic PCbM:

[0069] S2: Dissolve PVA in distilled water and stir continuously at 100℃ for 2 hours to form a PVA solution. Add bMOF to the PVA solution under nitrogen protection to make the bMOF content in the final hydrogel 1.2 mg / g.

[0070] S3: Dissolve 0.2g of chitosan in 10ml of water and add it to step S2. Then add 5ml of acetic acid solution to form a viscous sample solution. Stir the viscous solution at 45℃ for 45min, cast it onto a plastic mold, and vacuum process it. Then freeze it at -20℃ for 10h and thaw it at 20℃ for 5h. Repeat this cycle for 4 consecutive cycles.

[0071] The bimetallic MOF hydrogel dressing prepared in Example 1 was subjected to 500 μg / ml. -1 and 1000μgml -1 When incubated with Staphylococcus aureus and Escherichia coli, SEM analysis showed that Staphylococcus aureus and Escherichia coli exhibited severe morphological damage, demonstrating good antibacterial properties. The bimetallic MOF hydrogel dressing prepared in this application was found to have an antibacterial rate of 99.9%.

[0072] The skin penetration rate was 45.23 μg / cm³ after 24 hours. 2 The water retention capacity was 29.1%, the water contact angle was close to 18%, the water vapor transmission rate was 2120.1 g / m² 24h, the cell viability was 99.6% when testing biocompatibility, the coagulation time was 242.56 s, and the blood loss in the mouse tail amputation experiment was 23.0 mg.

[0073] Example 2

[0074] The preparation method of bimetallic MOF hydrogel dressing includes the following steps:

[0075] Preparation of bMOF (S1): Dissolve 0.272g AgNO3 and 0.448g Cu(NO3)2·3H2O in 10-15ml deionized water. Disperse 0.14g H2PYDC in 8-15ml deionized water by ultrasonication. Mix the two solutions together and seal them in a steel autoclave. Heat at 100℃ for 24h, then centrifuge at 4800rpm for 10min. After precipitation, discard the supernatant. Wash the precipitate three times and dry it at 50℃ for 4h to obtain bMOF. The content of Ag ions in bMOF is 1.6mmol and the content of Cu ions is 2.4mmol.

[0076] Synthetic PCbM:

[0077] S2: Dissolve PVA in distilled water and stir continuously at 80°C for 2 hours to form a PVA solution. Add bMOF to the PVA solution under nitrogen protection to make the bMOF content in the final hydrogel 1.2 mg / g.

[0078] S3: Dissolve 0.2g of chitosan in 10ml of water and add it to step S2. Then add 5ml of acetic acid solution to form a viscous sample solution. Stir the viscous solution at 45℃ for 45min, cast it onto a plastic mold, and vacuum process it. Then freeze it at -20℃ for 10h and thaw it at 20℃ for 5h. Repeat this cycle for 4 consecutive cycles.

[0079] The bimetallic MOF hydrogel dressing prepared in Example 2 was subjected to a 500 μg / ml test. -1 After incubation with Staphylococcus aureus and Escherichia coli, SEM analysis showed that Staphylococcus aureus and Escherichia coli suffered severe morphological damage, proving that the sample had good antibacterial properties. The bimetallic MOF hydrogel dressing prepared in this application had an antibacterial rate of 95.7%.

[0080] The skin penetration rate was 47.68 μg / cm³ after 24 hours. 2 It has a water retention capacity of 28.2%, a water contact angle of nearly 18%, a water vapor transmission rate of 2011.1 g / m²24h, a cell viability of 99.1% during biocompatibility testing, a coagulation time of 277.22 s, and a blood loss of 68.1 mg in a mouse tail amputation experiment.

[0081] Example 3

[0082] The preparation method of bimetallic MOF hydrogel dressing includes the following steps:

[0083] Preparation of bMOF (S1): 0.17 g AgNO3 and 0.561 g Cu(NO3)2·3H2O were dissolved in 10-15 ml of deionized water. 0.14 g H2PYDC was ultrasonically dispersed in 8-15 ml of deionized water. The two solutions were mixed together and placed in a steel autoclave for sealing. The autoclave was heated at 120 °C for 24 h, then centrifuged at 4800 rpm for 10 min. After precipitation, the supernatant was discarded. The precipitate was washed three times and dried at 50 °C for 4 h to obtain bMOF. The bMOF contained 1 mmol of Ag ions and 3 mmol of Cu ions.

[0084] Synthetic PCbM:

[0085] S2: Dissolve PVA in distilled water and stir continuously at 90°C for 2 hours to form a PVA solution. Add bMOF to the PVA solution under nitrogen protection to make the bMOF content in the final hydrogel 1.2 mg / g.

[0086] S3: Dissolve 0.2g of chitosan in 10ml of water and add it to step S2. Then add 5ml of acetic acid solution to form a viscous sample solution. Stir the viscous solution at 45℃ for 45min, cast it onto a plastic mold, and vacuum process it. Then freeze it at -20℃ for 10h and thaw it at 20℃ for 5h. Repeat this cycle for 4 consecutive cycles.

[0087] The bimetallic MOF hydrogel dressing prepared in Example 3 was subjected to a 500 μg / ml test. -1 After incubation with Staphylococcus aureus and Escherichia coli, SEM analysis showed that Staphylococcus aureus and Escherichia coli suffered severe morphological damage, proving that the sample had good antibacterial properties. The bimetallic MOF hydrogel dressing prepared in this application had an antibacterial rate of 95.8%.

[0088] The skin penetration rate was 46.22 μg / cm³ after 24 hours. 2 It has a water retention capacity of 27.9%, a water contact angle of nearly 17%, a water vapor transmission rate of 1990.9 g / m² 24h, a cell viability of 93.7% during biocompatibility testing, a coagulation time of 277.5 s, and a blood loss of 62.3 mg in a mouse tail amputation experiment.

[0089] Example 4

[0090] The preparation method of bimetallic MOF hydrogel dressing includes the following steps:

[0091] Preparation of bMOF (S1): 0.408 g AgNO3 and 0.299 g Cu(NO3)2·3H2O were dissolved in 10-15 ml of deionized water. 0.14 g H2PYDC was ultrasonically dispersed in 8-15 ml of deionized water. The two solutions were mixed together and sealed in a steel autoclave. The Ag ion content was 2.4 mmol and the Cu ion content was 1.6 mmol. The mixture was heated at 120 °C for 24 h, then centrifuged at 5000 rpm for 10 min. After precipitation, the supernatant was discarded. The precipitate was washed three times and dried at 50 °C for 4 h to obtain bMOF. The bMOF contained 2.4 mmol of Ag ions and 1.6 mmol of Cu ions.

[0092] Synthetic PCbM:

[0093] S2: Dissolve PVA in distilled water and stir continuously at 100℃ for 2 hours to form a PVA solution. Add bMOF to the PVA solution under nitrogen protection to make the bMOF content in the final hydrogel 1.2 mg / g.

[0094] S3: Dissolve 0.2g of chitosan in 10ml of water and add it to step S2. Then add 10ml of acetic acid solution dropwise to form a viscous sample solution. Stir the viscous solution at 45℃ for 45min, cast it onto a plastic mold, and vacuum process it. Then freeze it at -15℃ for 10h and thaw it at 30℃ for 5h. Repeat this cycle for 5 consecutive cycles.

[0095] The bimetallic MOF hydrogel dressing prepared in Example 4 was subjected to a 500 μg / ml test. -1 After incubation with Staphylococcus aureus and Escherichia coli, SEM analysis showed that Staphylococcus aureus and Escherichia coli suffered severe morphological damage, proving that the sample had good antibacterial properties. The bimetallic MOF hydrogel dressing prepared in this application had an antibacterial rate of 95.1%.

[0096] The skin penetration rate was 47.88 μg / cm³ after 24 hours. 2 It has a water retention capacity of 27.3%, a water contact angle of nearly 20%, a water vapor transmission rate of 1897.3 g / m²24h, a cell viability of 93.6% during biocompatibility testing, a coagulation time of 264.96 s, and a blood loss of 56.3 mg in a mouse tail amputation experiment.

[0097] Example 5

[0098] The preparation method of bimetallic MOF hydrogel dressing includes the following steps:

[0099] Preparation of bMOF (S1): Dissolve 0.51g AgNO3 and 0.187g Cu(NO3)2·3H2O in 10-15ml deionized water. Disperse 0.14g H2PYDC in 8-15ml deionized water by ultrasonication. Mix the two solutions together and seal them in a steel autoclave. Heat at 120℃ for 24h, then centrifuge at 5000rpm for 10min. After precipitation, discard the supernatant. Wash the precipitate three times and dry it at 50℃ for 4h to obtain bMOF. The content of Ag ions in bMOF is 3mmol and the content of Cu ions is 1mmol.

[0100] Synthetic PCbM:

[0101] S2: Dissolve PVA in distilled water and stir continuously at 100℃ for 2 hours to form a PVA solution. Add bMOF to the PVA solution under nitrogen protection to make the bMOF content in the final hydrogel 1.2 mg / g.

[0102] S3: Dissolve 0.2g of chitosan in 10ml of water and add it to step S2. Then add 10ml of acetic acid solution dropwise to form a viscous sample solution. Stir the viscous solution at 45℃ for 45min, cast it onto a plastic mold, and vacuum process it. Then freeze it at -15℃ for 10h and thaw it at 30℃ for 5h. Repeat this cycle for 5 consecutive cycles.

[0103] The bimetallic MOF hydrogel dressing prepared in Example 5 was subjected to a 1000 μg / ml test. -1 After incubation with Staphylococcus aureus and Escherichia coli, SEM analysis showed that Staphylococcus aureus and Escherichia coli suffered severe morphological damage, proving that the sample had good antibacterial properties. The bimetallic MOF hydrogel dressing prepared in this application had an antibacterial rate of 99.9%.

[0104] The skin penetration rate was 48.08 μg / cm³ after 24 hours. 2 The water retention capacity was 26.7%, the water contact angle was close to 19%, the water vapor transmission rate was 1892.7 g / m² 24h, the cell viability was 93.6% when testing biocompatibility, the coagulation time was 255.96 s, and the blood loss in the mouse tail amputation experiment was 55.2 mg.

[0105] Comparative Example 1

[0106] Based on Example 1, the difference is that CS was not added.

[0107] The bimetallic MOF hydrogel dressing prepared in Comparative Example 1 was subjected to a 500 μg / ml solution. -1After incubation with Staphylococcus aureus and Escherichia coli, SEM analysis showed severe morphological damage to both bacteria, demonstrating the good antibacterial properties of the sample. The bimetallic MOF hydrogel dressing prepared in this application achieved an antibacterial rate of 95.3%.

[0108] The water retention capacity is 40.7%, the water contact angle is close to 21%, and the water vapor transmission rate is 1766.7 g / m³. 2 At 24 hours, the cell viability was 88.0%, the clotting time was 341.72 seconds, and the blood loss from tail amputation in mice was 227.9 mg.

[0109] Comparative Example 2

[0110] Based on Example 1, the difference is that bMOF was not added, and PC dressing was prepared.

[0111] The PC dressing prepared in Comparative Example 2 was subjected to a 500 μg / ml test. -1 The samples were incubated with Staphylococcus aureus and Escherichia coli, respectively. SEM analysis showed that Staphylococcus aureus and Escherichia coli did not show severe morphological damage, indicating that the antibacterial properties of the samples were average, with an antibacterial rate of 6%.

[0112] The water retention capacity was 47.1%, the water contact angle was close to 16%, the water vapor transmission rate was 1698.1 g / m²24h, the cell viability was 99.2% when the biocompatibility was tested, the coagulation time was 371.04 s, and the blood loss from tail amputation in mice was 79.0 mg.

[0113] Comparative Example 3

[0114] Based on Example 1, the difference is that silver nitrate was not added, and PCCuM dressing was prepared.

[0115] Comparative Example 4

[0116] Based on Example 1, the difference is that copper nitrate was not added, and PCAgM dressing was prepared.

[0117] The dressings prepared in Examples 1-5 and Comparative Examples 1-4 were tested for antibacterial properties, breathability, and biocompatibility. The test results are shown in Table 1.

[0118] in:

[0119] ① The specific method for the antibacterial experiment was as follows: PC hydrogel, PCAgM hydrogel, PCCuM hydrogel, and PCbM hydrogel were incubated with bacterial suspension at 37℃ and 120 rpm for 12 h to explore the antibacterial properties of the hydrogels. After 12 h of incubation, 100 μL of bacterial suspension was spread on LB solid medium. The medium was incubated overnight at 37℃, and the number of colonies on the plates was calculated using Image J.

[0120] ② The specific test method for the water contact angle is as follows: The water contact angle of the sample is measured using a high-speed camera. Approximately 3 μL of ultrapure water is dropped onto the clean surface of the hydrogel dressing using a probe. The water contact angle is calculated using software, and three sets of repeated experiments are performed, with the average value taken.

[0121] ③ The specific test method for water retention is as follows: Place the sample in PBS buffer in a 37°C oven until it reaches equilibrium. Remove the sample and weigh it periodically until the sample mass no longer decreases. The water retention capacity (WR) is calculated as follows:

[0122] WR(%) = W t / W e ×100%

[0123] W t W is the weight of the sample at time t. e This is the weight of the sample after equilibration.

[0124] ④ The specific test method for water vapor transmission rate is as follows: Fix a 35mm diameter sample in the mouth of a 25mm diameter beaker containing 10mL of water, and place it in an incubator at 37℃ and 35% relative humidity. Weigh the system at regular intervals. Calculate the water vapor transmission rate (WVTR) using the following formula:

[0125] WVTR(%)=(WV loss ) / At×100%

[0126] WV loss This refers to the weight reduction over a period of time. At refers to the area of ​​the test area, measured in meters (m²). 2 Each experiment was repeated three times, and the average value was taken.

[0127] ⑤ The specific testing method for the mouse tail amputation experiment was as follows: Twelve 8-week-old male BALB / c mice were selected and divided into 4 groups. Mice were anesthetized with isoflurane before the experiment. The samples were applied to the mouse tail amputation hemorrhage model to verify the tissue adhesion and hemostasis of the samples. In the tail amputation model, the tail was amputated 3 cm from the tail tip; in the liver hemorrhage model, the samples were applied immediately after exposing the wound, and the bleeding area was photographed at different time points. The amount of bleeding on the filter paper was weighed after each hemorrhage test, and the hemostasis time was recorded. A blank control group was also set up.

[0128] ⑥ The specific testing method for cell viability assay is as follows: Mouse L929 cells were inoculated at 1×10⁻⁶ cells per cell line. -5Cells were seeded at a density of 10% fetal bovine serum in 96-well plates of Dulbecco's modified Eagle's medium (DMEM). 5 mg of PC, PCAgM, PCCuM, and PCbM samples were sterilized by UV for 1 h and then incubated at 37°C with 5% CO2 for 24 h, followed by another 24 h incubation. 10 μL of a cell counting kit (CCK-8) was added to each well and incubated for 3 h. The absorbance of the samples was then measured at 450 nm using enzyme-labeled (ThermoFisher, Multiskan FC) plates.

[0129] Table 1 Performance Test Table

[0130]

[0131]

[0132] Referring to Table 1, the PCbM dressing prepared in this application has an antibacterial rate of not less than 99.9%, a skin penetration of not less than 40 μg / cm, a water retention of 25-30%, a water contact angle of 17-20%, a water vapor transmission rate of 1800-2200 g / m² 24h, a cell viability of not less than 90%, negligible cytotoxicity, a coagulation time of not more than 290 s, and a blood loss of not more than 70 mg in mouse tail amputation experiments.

[0133] refer to Figure 1 As shown, Figure 1 The diagram shows a comparison of the antibacterial properties of Example 1 and Comparative Examples 2-4. The test results showed that PCbM had an antibacterial rate of 99.9%, the PC dressing in Comparative Example 2 had an antibacterial rate of 6%, the PCAgM dressing in Comparative Example 4 had an antibacterial rate of 95.3%, and the PCCuM dressing in Comparative Example 3 had an antibacterial rate of 95.1%. The PC dressing showed significantly worse antibacterial performance compared to the PCbM dressing. Although the antibacterial rates of the PCAgM and PCCuM dressings were slightly lower than those of PCbM, PCAgM had a poor healing effect. When PCCuM was single-loaded, a large amount of copper ions were released, resulting in higher toxicity (99.4% cytotoxicity).

[0134] refer to Figure 2 As shown, Figure 2The diagram shows a comparison of cell viability between Example 1 and Comparative Examples 2-4 of this application, with a blank control group (Control) also included. The vertical axis represents cell viability. From the diagram, it can be seen that the cell viability of the PCbM dressing in Example 1 is 99.6%, the cell viability of the PC dressing in Comparative Example 2 is 99.2%, the cell viability of the PCCuM dressing in Comparative Example 3 is only 92.7%, and the cell viability of the PCAgM dressing in Comparative Example 4 is only 92.9%. Although the cell viability of the PC dressing is similar to that of the PCbM dressing, the antibacterial properties of the PC dressing are poor; its antibacterial rate is less than one-tenth of that of this application.

[0135] refer to Figure 3 As shown, Figure 3 The accompanying graph shows a comparison of water vapor transmission rate (WVTR) between Example 1 of this application and Comparative Examples 2-4. (Refer to...) Figure 3 As shown, the water retention of the PCbM dressing in Example 1 was 29.1%, the water retention of the PC dressing in Comparative Example 2 was 47.1%, the water retention of the PCCuM dressing in Comparative Example 3 was 47.9%, and the water retention of the PCAgM dressing in Comparative Example 4 was 42.2%. Both excessive and insufficient water retention are detrimental to wound healing. The PCbM dressing of this application has a moderate water retention of 25-30% and a water vapor transmission rate greater than that of PC, PCAgM, and PCCuM dressings. It can provide a moist environment for wound healing and promote gas exchange to a certain extent, thus accelerating wound healing. It is an ideal wound dressing.

[0136] refer to Figure 4 As shown, Figure 4 The figure shows a test diagram of the hemostatic performance of the PCbM dressing of this application applied to mice after tail amputation in Example 1 of this application. Figure 5 The diagram shows the hemostatic performance of the PCbM dressing of this application applied to mice after tail amputation in Example 1 of this application, with a blank control group also included. Figure 4 The left ordinate represents blood loss, and the right ordinate represents clotting time. In the mouse tail amputation experiment, the blood loss with PCbM dressing was only 23.0 mg, while the blood loss in the blank control group reached 230.0-240.0 mg. (Reference) Figure 4 and Figure 5 As can be seen, the amount of blood loss is significantly reduced by using PCbM dressing, indicating that this application has good hemostatic function, good adhesion, and is conducive to wound healing. In the mouse tail amputation experiment, the clotting time of PCbM is only 240-255s, while the clotting time is 360s-370s if this application is not used. It can be seen that this application can greatly improve the wound clotting rate and shorten the wound healing time.

[0137] refer to Figure 6 As shown, Figure 6 The diagram shows a test graph of the hemostatic performance of the PCbM dressing applied to a mouse liver wound in Example 1 of this application, with a blank control group also included. The left vertical axis represents blood loss, and the right vertical axis represents clotting time. In the mouse liver wound experiment, the blood loss with the PCbM dressing was only 105 mg, while the blood loss in the blank control group reached 580-600 mg. The blood loss with the PCbM dressing significantly decreased, indicating that this application has good hemostatic function, good adhesion, and is conducive to wound healing. In the mouse liver wound experiment, the clotting time of the PCbM dressing was only 200-230 s, while the clotting time without this application was 310-350 s.

[0138] Figure 7 This paper shows a control group diagram illustrating the wound-healing effect of Example 1 of this application in mice. Figure 8 The test diagram of the wound area of ​​mice in Example 1 of this application is shown. The wound area of ​​mice after 7 days is no more than 21%, and the wound area of ​​mice after 14 days is no more than 6%. It can be seen that the PCbM dressing of this application has a good wound healing function.

[0139] In summary, the PCbM dressing of this application exhibits excellent performance in terms of antibacterial properties, adhesion, healing promotion, and biocompatibility.

[0140] The above description is merely an embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of this application should be included within the scope of the claims of this application.

Claims

1. A bimetallic MOF hydrogel dressing to promote wound healing, characterized in that, The bimetallic MOF hydrogel dressing is composed of a bimetallic organometallic framework loaded on a multifunctional hydrogel. The bimetallic organometallic framework uses 3,5-pyridinedicarboxylic acid as a ligand. The bimetal in the bimetallic organometallic framework is Ag + and Cu 2+ ; The multifunctional hydrogel is composed of PVA and chitosan; The preparation method of the bimetallic MOF hydrogel dressing includes the following steps: S1: The bimetallic organometallic framework is obtained by mixing the bimetal with the ligand and heating; specifically, AgNO3, Cu(NO3)2·3H2O and ligand H2PYDC are dissolved in deionized water, mixed evenly, and then sealed in an autoclave and heated to obtain the bimetallic organometallic framework. S2: Add the bimetallic organometallic framework to the PVA solution for mixing and heating; specifically, heat and dissolve the PVA to obtain a PVA solution, and add the bimetallic organometallic framework to the PVA solution under nitrogen protection, so that the content of the bimetallic organometallic framework in the solution is 1-1.2 mg / g. S3: Add hydrogel solution to step S2 and heat to obtain a viscous sample solution; specifically, dissolve 0.2-0.3g of chitosan and add it to step S2, then add 5-15ml of acetic acid solution to obtain a viscous sample solution. S4: The viscous sample solution is subjected to cyclic freezing and thawing to obtain a bimetallic MOF hydrogel dressing; specifically, the prepared viscous sample solution is cast onto a plastic mold, vacuum treated, and then the mold is frozen at -20℃ to -15℃ and thawed at 20-30℃, and the cycle is repeated for 4-5 times to obtain the bimetallic MOF hydrogel dressing. In step S1, the heating temperature is 100-120℃; The heating temperature in step S2 is 80-100℃; The heating temperature in step S3 is 45-60℃; In this case, the mass ratio of silver ions: copper ions: ligands is 0.17~0.96:0.18~0.57:0.14; By mass ratio, bMOF:PVA:CS is 0.1~2%:5~10%:1~2%.

2. The bimetallic MOF hydrogel dressing of claim 1, wherein, The bimetallic MOF hydrogel dressing has an antibacterial rate of greater than 95%. And / or clotting time less than 300s.

3. The bimetallic MOF hydrogel dressing of claim 1, wherein, The heating temperature in step S1 is 120°C; And / or the heating temperature in step S2 is 100°C; The heating temperature in step S3 is 45°C.

4. The application of the bimetallic MOF hydrogel dressing as described in any one of claims 1-3 in the preparation of antibacterial materials.

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