Iron-based MOF derived carbon modified CS-BA / pva hydrogel, preparation method and application thereof

Abstract

The present application relates to a kind of iron-based MOF derived carbon modified CS-BA / PVA hydrogel, including hydrogel matrix and the functional nanomaterial in-situ composite in the inside of the hydrogel matrix, the hydrogel matrix is the reversible double-network framework formed by the crosslinking of benzene boric acid modified chitosan CS-BA and polyvinyl alcohol PVA by borate ester dynamic covalent bond, the functional nanomaterial is MIL-101-700 porous carbon nanoparticles.Preparation method includes the following steps: S1, preparation MIL-101-700;S2, preparation CS-BA;S3, preparation iron-based MOF derived carbon modified CS-BA / PVA hydrogel.The present application hydrogel realizes double bacteriostasis by triple nanometer enzyme antioxidant anti-inflammatory, photothermal synergistic Fenton catalysis hydroxyl radical, has extremely high clinical application value and industrialization prospect in the field of wound repair.

Description

Technical Field

[0001] This invention relates to the field of biomedical polymer materials technology, and in particular to an iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel, its preparation method, and its applications. Background Technology

[0002] Hydrogels, due to their high water content, good flexibility, biocompatibility, and extracellular matrix-like structural characteristics, have been widely used in biomedical materials, wound care, and drug delivery. Among them, composite hydrogels based on chitosan and polyvinyl alcohol have become a research hotspot in medical gel materials due to their advantages such as readily available and biodegradable raw materials and tunable mechanical properties.

[0003] Chitosan molecules are rich in amino and hydroxyl groups, which not only allow it to form stable dual-network structures with polyvinyl alcohol through hydrogen bonding, but also possess natural antibacterial properties, inhibiting the growth of common pathogenic bacteria, making it suitable for preparing antibacterial wound dressings. To impart multi-stimuli responsiveness to hydrogels, such as glucose and pH, existing technologies often employ phenylboronic acid grafting modification of chitosan to prepare phenylboronic acid-modified chitosan (CS-BA). The modified chitosan can form dynamic borate ester bonds, giving the hydrogel self-healing, tissue adhesion, and intelligent controlled-release properties, further expanding its application scenarios.

[0004] However, traditional CS-BA / PVA dual-network hydrogels still have significant shortcomings: First, these hydrogels rely solely on chitosan to achieve a single antibacterial effect, resulting in a limited antibacterial mechanism and efficiency, making it difficult to achieve ideal antibacterial effects on wounds with high bacterial loads; Second, pure polymer hydrogels have low specific surface area and lack pollutant adsorption and photothermal response functions, resulting in relatively limited functionality; Third, the network structure of conventional polymer gels generally has low stability, and long-term use can easily lead to problems such as excessive swelling and decreased mechanical properties.

[0005] To improve the overall performance of hydrogels, current research attempts to introduce inorganic functional materials into polymeric hydrogels. Metal-organic frameworks (MOFs) have advantages such as high porosity, large specific surface area, and designable structures. Among them, the MIL series of MOFs have shown outstanding performance in adsorption, catalysis, and photothermal conversion. While directly incorporating MIL materials into hydrogels can improve adsorption capacity to some extent, the original MOF materials have poor thermal stability and are prone to framework collapse and loss of active sites during use. Furthermore, the powder tends to agglomerate in the gel system, resulting in uneven dispersion and ultimately a significant decrease in the overall performance of the material.

[0006] Therefore, there is an urgent need to develop a composite hydrogel material that combines multiple stimulus responses, efficient synergistic antibacterial properties, excellent mechanical stability, and adsorption and photothermal functions, while simplifying the preparation process and ensuring that the functional materials are uniformly dispersed in the gel matrix to meet the practical application needs of medical antibacterial dressings, smart drug carriers, and other applications. Summary of the Invention

[0007] Therefore, it is necessary to address the problems of existing technologies, such as the single antibacterial mode and limited bactericidal efficiency of CS-BA / PVA dual-network hydrogels, the easy aggregation and poor thermal stability of directly introducing original MOF materials, and the single function and insufficient mechanical stability of pure polymer gels. To provide an iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel, its preparation method and application, this paper proposes a method for preparing and applying it.

[0008] An iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel includes a hydrogel matrix and functional nanomaterials in situ composited within the hydrogel matrix. The hydrogel matrix is ​​a reversible dual-network framework formed by the cross-linking of phenylboronic acid-modified chitosan CS-BA and polyvinyl alcohol PVA via dynamic covalent bonds of borate esters. The functional nanomaterials are MIL-101-700 porous carbon nanoparticles.

[0009] As a preferred embodiment, the MIL-101-700 porous carbon nanoparticles are obtained by high-temperature carbonization of MIL-101.

[0010] A method for preparing iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel as described above includes the following steps: S1. Reaction of ferric chloride hexahydrate with amino-terephthalic acid yields MIL-101. After high-temperature carbonization, MIL-101 is obtained as MIL-101-700. S2. Dissolve chitosan in solvent A to obtain CS solution. Dissolve 4-carboxyphenylboronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in solvent B to obtain mixture C. Add mixture C to CS solution to react and obtain CS-BA. S3. Mix MIL-101-700 aqueous solution with a concentration of 2 mg / mL, CS-BA aqueous solution with a concentration of 30 mg / mL, and polyvinyl alcohol with a concentration of 100 mg / mL evenly to obtain iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel.

[0011] As a preferred embodiment, the molar ratio of ferric chloride hexahydrate to aminoterephthalic acid in step S1 is 0.7 to 0.9:1.

[0012] As a preferred embodiment, the high-temperature carbonization temperature in step S1 is 700°C.

[0013] As a preferred embodiment, the molar ratio of chitosan, 4-carboxyphenylboronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in step S2 is 1:1:1.25:1.25.

[0014] As a preferred embodiment, in step S2, solvent A is an aqueous solution of acetic acid with a mass fraction of 1%, and solvent B is ethanol.

[0015] As a preferred embodiment, the polyvinyl alcohol in step S3 is type 1799 polyvinyl alcohol.

[0016] As a preferred embodiment, the volume ratio of MIL-101-700, CS-BA and polyvinyl alcohol in step S3 is 2:9:9.

[0017] The iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel prepared by the method described above achieves dual antibacterial effects through triple nanoenzyme anti-oxidation and anti-inflammation, and photothermal synergistic Fenton catalysis to generate hydroxyl radicals.

[0018] The iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel prepared by the method described above is used to prepare wound dressings.

[0019] This invention introduces Fe3O4-derived carbon-based nanomaterials derived from MIL-101 carbonized at 700℃, wherein Fe²⁺ is present in the material. + / Fe³ + The reversible variable valence structure endows the material with triple nanozyme activities: SOD-like, CAT-like, and POD-like. The SOD-like catalyzes the disproportionation of superoxide anions in the wound to scavenge toxic free radicals; the CAT-like decomposes excess H2O2 in the wound to avoid oxidative damage to normal cells; and the POD-like utilizes endogenous H2O2 in the wound to catalyze the generation of hydroxyl radicals. The three enzymes work synergistically to precisely regulate the ROS level in the wound, significantly inhibiting oxidative stress and excessive inflammatory response, fundamentally improving the microenvironment of infected wounds, and accelerating the proliferation of granulation tissue and epidermal cells.

[0020] MIL-101-700 combines the near-infrared photothermal effect of a carbon skeleton with the catalytic properties of Fe-based Fenton-like materials. The composite hydrogel achieves a photothermal conversion efficiency of 44.67%. Under 808nm near-infrared light irradiation, local heating is achieved to physically destroy bacterial cell membranes at high temperatures. At the same time, it catalyzes the in-situ generation of H2O2 to ·OH, which chemically inhibits bacterial bacteria by oxidizing and destroying their nucleic acids and proteins.

[0021] The matrix CS-BA and PVA rely on the dynamic covalent bonds of boric acid and hydroxyl groups to form the main cross-linking network. The MIL-101-700 surface is rich in oxygen-containing functional groups and forms reversible hydrogen bonds with the polymer chains, constructing a dual reversible cross-linking system of "dynamic covalent bonds + non-covalent hydrogen bonds". Rheological tests showed that G′>G′′ across the entire frequency range, and the three-dimensional network structure of the gel was stable. After large strain damage, the boric acid ester bonds and hydrogen bonds can be quickly broken and recombined, and the modulus recovery rate under alternating strain cycles is excellent.

[0022] MIL-101-700 porous particles are uniformly embedded in the hydrogel channels, filling the original macropores of the gel, refining the pore size, and forming a multi-level porous structure of polymer-carbon materials. Compared with blank CS-BA / PVA, the iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel has controllable porosity, and the interconnected porous structure can efficiently adsorb wound exudate while ensuring oxygen permeability to the wound, maintaining a moist healing environment, and avoiding secondary infection caused by exudate maceration.

[0023] The beneficial effects of this invention are as follows: By constructing a dynamic borate ester cross-linked matrix using chitosan grafted with phenylboronic acid and PVA, and introducing carbonized MIL-101-700 iron-based carbon nanomaterials, and relying on the synergistic advantages of triple nanoenzymes, high photothermal performance and reversible cross-linked matrix structure, a composite hydrogel integrating self-healing skin adhesion, exudate absorption, antioxidant and anti-inflammatory properties, and photothermal-Fenton synergistic antibacterial properties is prepared. It has good biocompatibility, no risk of drug resistance, and simple preparation process, and has extremely high clinical application value and industrialization prospects in the field of wound repair. Attached Figure Description

[0024] Figure 1 The Fourier transform infrared spectrum of MIL-101; Figure 2 Powder X-ray diffraction pattern (a) for MIL-101 and powder X-ray diffraction patterns (b) for MIL-101-600, MIL-101-700, and MIL-101-800. Figure 3 Scanning electron microscope image (a) of MIL-101 and scanning electron microscope image (b) of MIL-101-700. Figure 4 Hydration particle size diagrams for MIL-101 (a) and MIL-101-700 (b); Figure 5 X-ray photoelectron spectra of MIL-101-700 (a), high-resolution C 1s spectrum (b), high-resolution O 1s spectrum (c), high-resolution Fe 2p spectrum (d), and high-resolution N 1s spectrum (e). Figure 6 The image shows the UV absorption spectrum of a peroxidase-like substance, MIL-101-700. Figure 7 The ultraviolet absorption spectrum of the superoxide dismutase-like enzyme in MIL-101-700; Figure 8 The UV absorption spectrum of the catalase-like enzyme in MIL-101-700; Figure 9 This is a verification diagram of the generation of ·OH catalyzed by MIL-101-700; Figure 10 A comparison chart of the temperature rise curves for MIL-101-600, MIL-101-700, and MIL-101-800; Figure 11 The following figures show the temperature rise curves of MIL-101-700 at different concentrations after irradiation with an 808 nm laser for 5 min at power levels of 500 mW (a), 1000 mW (b), 1500 mW (c), and 2000 mW (d); the photothermal stability of MIL-101-700 under intermittent repetitive laser irradiation (808 nm, 2000 mW) (e); and the photothermal conversion efficiency of MIL-101-700 at 808 nm, 2000 mW (f). Figure 12 The infrared spectrum of chitosan (CS-BA) loaded with phenylboronic acid; Figure 13 The diagram shows the gelation process of the blank hydrogel CS-BA / PVA (a), the gelation process of the MIL-101-700@CS-BA / PVA hydrogel (b), and the self-healing process of the blank hydrogel CS-BA / PVA hydrogel. Figure 14 Scanning electron microscope images of blank hydrogel CS-BA / PVA (a) and MIL-101-700@CS-BA / PVA (b); Figure 15 A comparison of the porosity of blank hydrogel CS-BA / PVA and MIL-101-700@CS-BA / PVA; Figure 16 Frequency scan (a), strain scan (b) of blank hydrogel CS-BA / PVA and MIL-101-700@CS-BA / PVA, and alternating strain scan of blank hydrogel CS-BA / PVA. Figure 17 Photothermal stability of MIL-101-700@CS-BA / PVA under intermittent repetitive laser irradiation (808 nm, 1000 mW) (a) and photothermal conversion efficiency of MIL-101-700@CS-BA / PVA at 808 nm, 1000 mW (b). Detailed Implementation

[0025] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0026] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention. Example 1

[0027] Preparation of MIL-101-700 1) Take a clean beaker and add 30 mL of DMF solution. Then weigh 309 mg of ferric chloride hexahydrate (FeCl3·6H2O) and add it to the beaker. Stir or sonicate until completely dissolved. After the solution is completely clear, weigh 250 mg of amino-terephthalic acid (NH2-BDC) and add it to the beaker. Stir or sonicate until completely dissolved. After stirring the above solution at room temperature for 2 hours, transfer it to a microwave synthesis reactor. Microwave the reaction at 600 W and 120 °C. o C, 1 hour. After the reaction was complete and the instrument had cooled completely to room temperature, the reaction vessel was removed, the product was centrifuged (11000 rpm, 8 min), then washed twice with DMF and once with ethanol, and freeze-dried to obtain MIL-101; 2) Weigh 0.25 g of dry MIL-101 powder and spread it evenly in a quartz boat. Place the quartz boat in the center of the isothermal zone of the tube furnace. Then, under continuous nitrogen protection (flow rate maintained at 50 mL / min), raise the furnace temperature to 700 °C at a heating rate of 3 °C / min and hold at the target temperature for 1 h. After the high-temperature carbonization treatment, turn off the heating power and allow the sample to cool naturally to room temperature in a nitrogen flow. Collect the obtained black powder product and label it MIL-101-700. Example 2

[0028] Preparation of CS-BA 3g of chitosan (CS) was dissolved in 300ml of 1% acetic acid solution and stirred until a CS solution was formed. 4-Carboxyphenylboronic acid (BA), EDC·HCl, and NHS were completely dissolved in 40mL of ethanol to obtain mixture C. Mixture C was added to the CS solution and stirred for 24h, followed by dialysis and freeze-drying to obtain CS-BA. The molar ratio of chitosan, 4-carboxyphenylboronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N-hydroxysuccinimide was 1:1:1.25:1.25. Example 3

[0029] Preparation of iron-based MOF-derived carbon-modified CS-BA / PVA hydrogels The MIL-101-700 prepared in Example 1 was dissolved in ultrapure water to prepare a 2 mg / mL MIL-101-700 aqueous solution. 0.2 mL of the MIL-101-700 aqueous solution was added to 0.9 mL of a 100 mg / mL PVA solution and mixed well. Then, another 0.9 mL of a 30 mg / mL CS-BA solution was added to obtain an iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel, labeled as MIL-101-700@CS-BA / PVA hydrogel. The final concentration of MIL-101-700 in this hydrogel was 200 μg / mL.

[0030] Comparative Example 1 Preparation of MIL-101-600 It is basically the same as Example 1, except that the furnace temperature is raised to 600°C at a heating rate of 3°C per minute.

[0031] Comparative Example 2 Preparation of MIL-101-800 It is basically the same as Example 1, except that the furnace temperature is raised to 800°C at a heating rate of 3°C per minute.

[0032] Comparative Example 3 Preparation of blank hydrogel CS-BA / PVA The CS-BA prepared in Example 2 was dissolved in ultrapure water to prepare a solution with a concentration of 30 mg / ml. At the same time, the 1799 type polyvinyl alcohol (PVA) was dissolved in ultrapure water to prepare a solution with a concentration of 100 mg / ml. The polyvinyl alcohol solution was obtained by heating in an 80°C water bath. The two solutions were mixed in a volume ratio of 1:1 to obtain a blank hydrogel CS-BA / PVA.

[0033] Test Example 1 MIL-101 Fourier Transform Infrared Spectroscopy Experiment The MIL-101 prepared in step 1) of Example 1 was measured and analyzed using Fourier transform infrared spectroscopy, and the results are as follows: Figure 1 As shown.

[0034] Depend on Figure 1 It can be seen that MIL-101 is at 1655.8 cm. -1 The amino-terephthalic acid ligand-coated carboxyl group (-COO) appeared at the location of MIL-101. - The asymmetric stretching vibration of ) is due to the interaction between the ligand and Fe. 3+ The core characteristic peak of successful coordination and MOF framework formation; at 1578.5 cm⁻¹. -1 The C=C double bond stretching vibration of the amino-terephthalic acid ligand benzene ring skeleton was observed at 1384.5 cm⁻¹. -1 A coordinating carboxyl group (-COO) appeared at the position. - The symmetrical stretching vibration of ) with 1655.8 cm -1 The peaks appeared in pairs, further confirming the relationship between the carboxyl group and Fe. 3+ The bidental coordination mode; and at 1255 cm -1 The presence of in-plane bending vibrations of the CH bond in the amino-terephthalic acid ligand's benzene ring confirms the existence and structural integrity of the organic ligand. This preliminary indication suggests the successful synthesis of MIL-101.

[0035] Test Example 2 X-ray diffraction experiments of MIL-101, MIL-101-700, MIL-101-600 and MIL-101-800 X-ray diffraction was used to test MIL-101 prepared in step 1) of Example 1, MIL-101-700 prepared in Example 1, MIL-101-600 prepared in Comparative Example 1, and MIL-101-800 prepared in Comparative Example 2. The experimental results are as follows: Figure 2 As shown.

[0036] Depend on Figure 2 As can be seen from a, the high-intensity narrow peak indicates that MIL-101 has high crystallinity, and the sharp peak shape and stable baseline indicate that highly crystalline MIL-101 crystals were successfully synthesized via microwave-assisted synthesis. Figure 2As shown in Figure 2b, when the carbonization temperature reaches 600°C, the characteristic peaks of MIL-101 almost completely disappear, and two distinct broadened diffraction peaks appear at 2θ = 26° and 44°, which are attributed to the (002) and (100) crystal planes of graphitic carbon, respectively, confirming the formation of an amorphous carbon matrix. Notably, in the spectrum of MIL-101-700, in addition to the two broad peaks of carbon, new sharp diffraction peaks appear at 2θ = 30.1°, 35.5°, 43.1°, 57.0°, and 62.6°, the positions of which coincide with the standard card for Fe3O4. This indicates that during the carbonization process at 700°C, the iron nodes in MIL-101 are reduced and recrystallized into Fe3O4 nanoparticles. When the temperature is further increased to 800°C (MIL-101-800), the diffraction peak intensity of Fe3O4 is further enhanced and becomes sharper. At the same time, the carbon (002) peak shifts slightly to a higher angle and the half-width at half-maximum (WHM) narrows, indicating that the degree of graphitization of carbon and the crystallinity of Fe3O4 particles both increase with increasing temperature.

[0037] Test Example 3 Scanning electron microscopy experiments of MIL-101 and MIL-101-700 The MIL-101 prepared in step 1) of Example 1 and the MIL-101-700 prepared in Example 1 were tested using a scanning electron microscope. The experimental results are as follows: Figure 3 As shown.

[0038] Figure 3 Image a shows a typical SEM image of the original MIL-101, clearly showing that the material exhibits a uniform, smooth, regular octahedral morphology with a relatively concentrated particle size distribution and an average size of approximately 200 ± 30 nm. Figure 3 As shown in b, when the carbonization temperature is 700°C, the original octahedral morphology is basically preserved, but the particle surface becomes rough, with many wrinkles and pores. This may be because high-temperature carbonization transforms the metal components in MIL-101 into uniformly distributed metal oxide nanoparticles embedded in the carbon matrix. This structure allows the Fe3O4 nanoparticles to be highly dispersed on the porous carbon support, which is beneficial for exposing more active sites.

[0039] Test Example 4 MIL-101 and MIL-101-700 Hydrated Particle Size Determination The MIL-101 prepared in step 1) of Example 1 and the MIL-101-700 prepared in Example 1 were tested using a dynamic light scattering instrument. The experimental results are as follows: Figure 4 As shown.

[0040] Depend on Figure 4As shown, the hydrated particle size of the original MIL-101 nanoparticles is approximately 217.6 ± 12.3 nm, slightly larger than the dry particle size observed by SEM. This may be due to the adsorption of water molecules on the particle surface or slight swelling. The hydrated particle size of the MIL-101-700 nanoparticles is 247.6 ± 25.1 nm. The increase in particle size is mainly attributed to the fusion of particles during carbonization, the formation of a porous carbon framework, and the loading of metal oxide nanoparticles, resulting in an increase in hydrodynamic volume.

[0041] Test Example 5 MIL-101-700 X-ray photoelectron spectroscopy test The MIL-101-700 prepared in Example 1 was tested using X-ray photoelectron spectroscopy, and the experimental results are as follows: Figure 5 As shown in a, 5b, 5c, 5d and 5e.

[0042] Depend on Figure 5 As can be seen from the spectrum, the characteristic photoelectron peaks of C, O, Fe, and N elements are clearly visible, confirming that the MIL-101-700 material is composed of four elements: carbon, oxygen, iron, and nitrogen. Figure 5 b shows the high-resolution fine spectrum of the C 1s orbital, with the main peak located at 284.8 eV, attributed to C-C or C=C bonds in the carbon framework of the material. Secondary peaks appearing near 285.6 eV and 287.2 eV correspond to CO bonds and C=O / OC=O bonds, respectively. The presence of these oxygen-containing functional groups indicates a certain degree of oxidation on the surface of the carbon material. The high-resolution O 1s spectrum is shown below. Figure 5 As shown in c, its peak shape is relatively broad, and after fitting, it can be divided into two main components located at 530.1 eV and 531.5 eV. The former corresponds to lattice oxygen (O) in the metal oxide. 2- The latter belongs to hydroxyl (-OH) or chemically adsorbed oxygen species on the material surface. Figure 5 The d-axis represents the high-resolution fine spectrum of the Fe 2p orbital, with Fe 2p orbitals observed at binding energies of 710.8 eV and 724.6 eV, respectively. 3 / 2 and Fe 2p 1 / 2 The spin-orbit splitting peaks, with a spacing of approximately 13.8 eV, are typical characteristics of Fe3O4. Fe 2p 3 / 2 The peak can be further deconvolved into two peaks located at 710.5 eV and 712.3 eV, corresponding to Fe, respectively. 2+ and Fe 3+ Species. Furthermore, a distinct satellite peak was observed at approximately 719.0 eV, the presence of which is attributed to Fe. 3+Characteristic signals. Based on the peak position, peak shape, and satellite peak characteristics of the Fe 2p spectrum, it can be confirmed that the iron element in MIL-101-700 mainly exists in the form of Fe3O4, which is consistent with the conclusions of X-ray diffraction analysis.

[0043] Test Example 6 MIL-101-700 Peroxidase (POD) Activity Assay Reagent preparation: MIL-101-700 solution: Weigh 2 mg of MIL-101-700 prepared in Example 1 and add it to 1 mL of PBS (pH 5.5) solution. Disperse the mixture evenly by sonication to obtain the MIL-101-700 solution. TMB solution: Weigh 10 mg of 3,3′,5,5′-tetramethylbenzidine (TMB) and add it to 1 mL of dimethyl sulfoxide (DMSO) solution. Dissolve the TMB stock solution by sonication until homogeneous to obtain TMB stock solution. Then, pipette 0.3 mL of the TMB stock solution into a 10 mL centrifuge tube, add 2.7 mL of PBS (pH 5.5) solution, and sonicate until homogeneous to obtain TMB solution.

[0044] Hydrogen peroxide solution: Accurately pipette 0.1 mL of hydrogen peroxide (30%) solution into a 10 mL centrifuge tube, then add 0.879 mL of PBS (pH 5.5) solution and shake well to obtain a 1 M hydrogen peroxide stock solution; pipette 0.05 mL of the hydrogen peroxide stock solution into a 10 mL centrifuge tube, add 2.45 mL of PBS (pH 5.5) solution and shake well to obtain the hydrogen peroxide solution.

[0045] Experimental steps: Pipette 0.2 mL of MIL-101-700 solution, 0.2 mL of TMB solution, 0.2 mL of hydrogen peroxide solution, and 1.4 mL of PBS (pH 5.5) solution into a quartz cuvette. Use a UV-Vis spectrophotometer to measure the absorbance at 650 nm at nine time points: 0, 2, 4, 6, 8, 10, 12, 14, and 16 min. The results are as follows: Figure 6 As shown.

[0046] Depend on Figure 6It can be seen that with the addition of a small amount of H2O2, the absorbance at the maximum characteristic absorption peak of TMB at 650 nm fluctuated significantly in the first 2 minutes. This indicates that with the introduction of external H2O2, MIL-101-700 can rapidly catalyze the production of ·OH from H2O2, oxidizing TMB and resulting in a significant increase in absorbance at 650 nm. Finally, within the same time period, the absorbance at 650 nm increased more than without H2O2, mainly due to the introduction of external H2O2 and MIL-101-700's own production of H2O2 using oxygen as an electron acceptor. Both factors combined led to the accumulation of H2O2. Subsequently, MIL-101-700 catalyzed the production of ·OH from H2O2 through a Fenton-like reaction, intensifying TMB oxidation, and the absorbance at 650 nm gradually increased, indicating that MIL-101-700 possesses peroxidase-like activity.

[0047] Test Example 7 MIL-101-700 Superoxide Dismutase (SOD) Activity Assay Reagent preparation: MIL-101-700 solution: Weigh 2 mg of MIL-101-700 prepared in Example 1 and place it in 1 mL of Tris buffer. Disperse it evenly by sonication to obtain MIL-101-700 solution. NBT solution: Weigh 8.2 mg of nitrotetrazolium chloride (NBT) and place it in 5 mL of Tris buffer. Dissolve the NBT solution by sonication until homogeneous.

[0048] L-methionine solution: Weigh 71.6 mg of L-methionine and add it to 8 mL of Tris buffer. Dissolve the L-methionine solution by sonication.

[0049] Riboflavin solution: Weigh 6 mg of riboflavin into 8 mL of Tris buffer, and sonicate thoroughly to dissolve it evenly to obtain riboflavin stock solution. Take 200 μL of riboflavin stock solution and dilute it with 3.8 mL of Tris buffer to obtain riboflavin solution.

[0050] EDTA solution: Weigh 11.2 mg of ethylenediaminetetraacetic acid (EDTA) and add it to 3 mL of Tris buffer. Sonicate thoroughly to dissolve the EDTA stock solution. Take 800 μL of the EDTA stock solution and dilute it with 3.2 mL of Tris buffer to obtain the EDTA solution.

[0051] Experimental steps: Pipette 0.2 mL of MIL-101-700 solution, 0.1 mL of NBT solution, 0.5 mL of L-methionine solution, 0.1 mL of riboflavin solution, 0.1 mL of EDTA solution, and 1 mL of Tris buffer into a quartz cuvette; and replace the 0.2 mL MIL-101-700 solution with the same volume of Tris buffer, keeping the other solution volumes unchanged, to prepare a blank control solution. After 5 min in darkness followed by 5 min of illumination, the absorbance of both the blank and material groups was measured at 560 nm using a UV-Vis spectrophotometer. The results are as follows: Figure 7 As shown.

[0052] Superoxide dismutase (SOD) is a key antioxidant enzyme in wound healing, playing a central role in antibacterial activity and promoting wound repair. It specifically catalyzes the dismutation of superoxide anion free radicals produced in large quantities during infection, inflammation, and oxidative stress, converting toxic superoxide anion free radicals into H2O2 and O2. This effectively scavenges free radicals, reduces oxidative stress damage to cells and tissues, inhibits excessive inflammatory responses, reduces the release of inflammatory factors, and protects the stability of the wound microenvironment. Simultaneously, SOD regulates reactive oxygen species levels, reducing tissue oxidative damage, promoting granulation tissue proliferation and epidermal cell migration and repair, and also exerts an auxiliary antibacterial effect with the moderate amount of hydrogen peroxide generated during the reaction. Synergistically, SOD works with CAT and POD to construct a complete antioxidant defense system, ultimately reducing infection damage and accelerating wound healing. Figure 7 As shown, at 560 nm, the absorbance of the material group is lower than that of the blank control group, indicating that MIL-101-700 has superoxide dismutase-like activity.

[0053] Test Example 8 MIL-101-700 Catalase (CAT) Activity Assay MIL-101-700 solution: Weigh 4 mg of MIL-101-700 prepared in Example 1 and place it in 1 mL of Tris buffer. Disperse it evenly by sonication to obtain MIL-101-700 solution. H2O2 solution: Measure 0.5 mL of 30% H2O2 into 4.379 mL of PBS buffer, and sonicate thoroughly to dissolve it evenly to obtain mother solution 1. Then take 0.1 mL of mother solution 1 and add it to 9.9 mL of PBS buffer and mix evenly to obtain mother solution 2. Then take 1 mL of mother solution 2 and add it to 4 mL of PBS buffer and mix evenly to obtain H2O2 solution.

[0054] HRP solution: Weigh 1 mg of horseradish peroxidase (HRP) into 5 mL of PBS buffer, and sonicate thoroughly to dissolve and homogenize to obtain HRP solution.

[0055] ABTS solution: Weigh 43.89 mg of 2,2'-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) into 4 mL of PBS buffer, and sonicate thoroughly to dissolve and homogenize to obtain ABTS solution.

[0056] Experimental steps: Pipette 1.5 mL of PBS buffer, add 0.1 mL of MIL-101-700 solution and 0.1 mL of H2O2 solution, and incubate at room temperature for 30 min. Then add 0.1 mL of HRP solution and 0.2 mL of ABTS solution, and incubate for 5 min. Measure the absorbance at 500-700 nm using a UV-Vis spectrophotometer. Similarly, replace 0.1 mL of solution 1 with the same volume of PBS buffer, keeping the other solution volumes unchanged. Prepare a blank control solution using the same experimental procedure, and measure the absorbance at the same wavelength using a UV-Vis spectrophotometer for comparison with the absorbance of the material group. The results are as follows: Figure 8 As shown.

[0057] Catalase (CAT) is a crucial antioxidant enzyme in the body. During the healing of infected wounds, it primarily participates in clearing excess hydrogen peroxide, maintaining redox balance, reducing inflammatory damage, and promoting tissue repair. Its core function is to efficiently decompose H2O2 produced at the wound site due to oxidative stress, immune responses, and SOD catalysis, converting it into non-toxic H2O and O2. This prevents high concentrations of H2O2 from causing oxidative damage to wound cells, proteins, and DNA, thereby protecting the normal proliferation and differentiation of granulation tissue, fibroblasts, and epidermal cells. CAT can significantly reduce local oxidative stress levels, inhibit excessive inflammatory responses, reduce the release of inflammatory factors, and improve the wound microenvironment. Simultaneously, by rationally regulating the concentration of reactive oxygen species (ROS), it avoids the accumulation of free radicals that cause tissue damage while retaining adequate ROS to exert basic antibacterial effects. Synergistically with SOD and POD, it forms a complete antioxidant protection system, effectively reducing tissue damage caused by infection and accelerating epithelial regeneration, granulation tissue formation, and wound healing. Figure 8 As shown, at 500-700 nm, the absorbance of the material group is lower than that of the blank control group, indicating that MIL-101-700 has catalase-like activity.

[0058] Test Example 9 Electron spin resonance (ESR) detection of hydroxyl radicals (·OH) in MIL-101-700 MIL-101-700 prepared in Example 1 was mixed with H2O2 in PBS (pH 5.5), and DMPO (5,5-dimethyl-1-pyrrolline-N-oxide) was immediately added to capture free radicals. The mixture was rapidly transferred to a quartz capillary, and the results were detected on an ESR spectrometer within 1 minute of the start of the reaction. Figure 9 As shown.

[0059] Depend on Figure 9 It can be seen that the DMPO-·OH of MIL-101-700 shows a typical 1:2:2:1 quartet, indicating that MIL-101-700 has a good ability to generate ·OH.

[0060] Test Case 10 Photothermal performance testing of MIL-101-600, MIL-101-700 and MIL-101-800 Sample solutions: MIL-101-700 prepared by the examples, MIL-101-600 prepared by Comparative Example 1, and MIL-101-800 prepared by Comparative Example 2 were respectively prepared with deionized water to prepare sample solutions with a concentration of 200 μg / mL. Experimental steps: One mL of sample solution was placed in a 1.5 mL EP tube. An 808 nm near-infrared laser (power density 2 W) was used to irradiate the solution laterally, with the laser spot passing through the center of the liquid. The solution temperature change was recorded every 30 seconds using an infrared thermal imager. Irradiation continued for 5 minutes, and the temperature rise curve over those 5 minutes was recorded. The results are as follows: Figure 10 As shown.

[0061] Depend on Figure 10 It can be seen that under 808 nm near-infrared light irradiation, with a power of 2 W, the concentrations of carbonized MIL-101-600, MIL-101-700, and MIL-101-800 nanomaterials are all 200 μg / ml. After 5 min of light irradiation, it can be seen that MIL-101-700 has the highest heating temperature and stronger photothermal conversion capability.

[0062] Test Example 11 MIL-101-700 Photothermal Conversion Efficiency and Stability Test Sample solutions: Sample solutions with concentrations of 0, 50, 100, 150, and 200 μg / mL were prepared using MIL-101-700 prepared in the examples and deionized water. Experimental steps: One mL of sample solution was placed in a 1.5 mL EP tube. An 808 nm near-infrared laser was used with power densities of 0.5, 1.0, 1.5, and 2.0 W. After 5 min of illumination, the laser was turned off, and the solution temperature was recorded every 30 seconds. After the solution cooled for 5 min, the above operation was repeated 4 times. The heating-cooling curves of the material and the natural logarithm plot of the temperature change curve of the solution with increasing illumination time were plotted based on the recorded temperatures and time points. The photothermal conversion efficiency (η) of the material was calculated using the formula based on the heating-cooling curves. The specific calculation formula is as follows:

[0063] Where h is the heat transfer coefficient and S is the sample surface area. The maximum temperature, For ambient temperature, λ represents the heat endothermic in the pure solvent under laser irradiation, I represents the laser power, and Aλ represents the absorbance of the sample at 808 nm. Simultaneously, the same MIL-101-700 aqueous dispersion (200 μg / mL) was subjected to 5 irradiation-cooling cycles, and the results are as follows: Figure 11 As shown.

[0064] like Figure 11 As shown, a, b, c, and d are the temperature rise curves of MIL-101-700 at different concentrations under power of 500 mW, 1000 mW, 1500 mW, and 2000 mW, respectively, after irradiation with an 808 nm laser for 5 min. It can be seen that, at the same power, the temperature gradually increases with increasing material concentration; similarly, at the same concentration, the temperature gradually increases with increasing power, indicating that MIL-101-700 possesses good photothermal properties.

[0065] like Figure 11 As shown in e and f, the photothermal stability of MIL-101-700 under intermittent repetitive laser irradiation (808 nm, 2000 mW) indicates that the material has good stability. The photothermal conversion efficiency of MIL-101-700 is 34.34%, which both indicate that MIL-101-700 has good photothermal performance and stability.

[0066] Test Example 12 Fourier transform infrared spectroscopy experiments of CS and CS-BA Fourier transform infrared spectroscopy was used to test commercially available CS and CS-BA prepared in Example 2, and the results are as follows: Figure 12 As shown.

[0067] Depend on Figure 12 As shown, the characteristic absorption peaks of pure chitosan include: 3360 cm⁻¹ -1The broad peak at 2870 cm⁻¹ is attributed to the overlapping peaks of the stretching vibrations of OH and NH; -1 The weak peak at 1650 cm⁻¹ is due to CH stretching vibration; -1 and 1590 cm -1 The strong peaks at 710 cm⁻¹ correspond to the C=O stretching vibration of amide I and the NH bending vibration of amide II (originating from incompletely deacetylated residues), respectively. -1 This peak represents the out-of-plane bending vibration of the CH group of the benzene ring in 3-carboxyphenylboronic acid (BA). Pure chitosan (CS) lacks a benzene ring structure and shows no absorption at this position; the appearance of this peak in CS-BA directly proves that the benzene-containing BA has been successfully introduced. (At 1560 cm⁻¹) -1 The peak corresponds to the C=C skeletal stretching vibration of the BA benzene ring, superimposed with the characteristic absorption of the amide bond formed by the BA carboxyl group and the amino group on CS. Pure CS does not exhibit this characteristic peak, but the presence of this peak in CS-BA confirms that BA is covalently grafted onto CS via an amidation reaction. The synergistic appearance of these two characteristic peaks fully verifies the successful loading of 3-carboxyphenylboronic acid (BA) onto chitosan (CS). These FT-IR results clearly demonstrate that CS and BA undergo chemical cross-linking through dynamic borate ester bonds, successfully constructing a dual-network structure.

[0068] Test Example 13 Experiments on gelation and self-healing properties of MIL-101-700@CS-BA / PVA hydrogel and blank hydrogel 1) Record the gelation process of the blank hydrogel prepared in Comparative Example 3 and the MIL-101-700@CS-BA / PVA hydrogel prepared in Example 3. The results are as follows: Figure 13 As shown in Figures a and b; 2) A cylindrical hydrogel was completely cut in half lengthwise with a blade into two smaller pieces. One piece was stained with dye. The two fresh cut surfaces were then placed in close contact and left at room temperature without any external force applied. The result was as follows: Figure 13 As shown in c.

[0069] Depend on Figure 13 As shown in a and 13b, both the blank hydrogel and the MIL-101-700@CS-BA / PVA hydrogel were successfully gelled; Figure 13 As shown in c, the two cut parts re-fuse into a single unit, and the healed hydrogel can be lifted and bear its own weight without breaking. These phenomena indicate that CS-BA / PVA hydrogel has excellent self-healing properties.

[0070] Test Example 14 Scanning electron microscope images of MIL-101-700@CS-BA / PVA hydrogel and blank hydrogel Scanning electron microscopy was used to test the blank hydrogel prepared in Comparative Example 3 and the MIL-101-700@CS-BA / PVA hydrogel prepared in Example 3. The results are as follows: Figure 14 a and Figure 14 As shown in b.

[0071] Depend on Figure 14 a and Figure 14 b shows that the pore size of the hydrogel decreased after loading MIL-101-700, which initially indicates that MIL-101-700 was successfully encapsulated by CS-BA / PVA hydrogel.

[0072] Test Example 15 Porosity analysis experiments of MIL-101-700@CS-BA / PVA hydrogel and blank hydrogel The freeze-dried samples (the blank hydrogel prepared from Comparative Example 3 and the MIL-101-700@CS-BA / PVA hydrogel prepared from Example 3) were placed into containers with a volume of [missing information]. The sample was placed in anhydrous ethanol and allowed to stand for 10 minutes. Then, it was placed in a vacuum freeze dryer to degas until no small bubbles appeared on the sample surface. The volume of anhydrous ethanol at this point was recorded as [volume value missing]. Remove the sample; the remaining volume of anhydrous ethanol is recorded as follows: The porosity of the blank hydrogel and the MIL-101-700@CS-BA / PVA hydrogel were calculated according to the porosity formula, and the results are as follows. Figure 15 As shown; Porosity formula: .

[0073] Depend on Figure 15 It can be seen that MIL-101-700 successfully entered the pores of the CS-BA / PVA blank hydrogel.

[0074] Test Example 16 Rheological property analysis experiments of MIL-101-700@CS-BA / PVA hydrogel and blank hydrogel The blank hydrogel prepared by Comparative Example 3 and the MIL-101-700@CS-BA / PVA hydrogel prepared by Example 3 were tested using a rotational rheometer. The test results are as follows: Figure 16 a, Figure 16 b and Figure 16 As shown in c.

[0075] Depend on Figure 16As shown in Figure 16b, within the test frequency range, the storage modulus G' of all samples was consistently greater than the loss modulus G'', consistent with the typical elastic-dominated hydrogel characteristics, proving that both hydrogels formed a stable three-dimensional network structure. The G' and G'' of the blank hydrogel CS-BA / PVA were significantly higher than those of the composite hydrogel MIL-101-700@CS-BA / PVA. The G' and G'' of the composite hydrogel showed a slow increasing trend with increasing frequency, indicating that the introduction of MIL-101-700 did not disrupt the gel network, but only moderated the mechanical strength of the gel to a certain extent, while maintaining good frequency stability. Figure 16b shows that the G' and G'' of both hydrogels remained almost constant during the test time, without significant attenuation, demonstrating their excellent structural stability and resistance to deformation under small strain, and that the gel network could maintain stability under continuous shear. The G' and G'' of the composite hydrogel were still lower than those of the blank hydrogel, consistent with the frequency scan results, indicating that the loading of MIL-101-700 had a certain regulatory effect on the basic mechanical strength of the gel, without disrupting its structural stability. As shown in Figure 16c, during the 1% small strain stage, G' of CS-BA / PVA is always greater than G'', indicating that the hydrogel network remains intact. During the 550% large strain stage, G' and G'' decrease significantly, and G'' even surpasses G', indicating that the hydrogel network is destroyed and a sol-gel transition occurs. When the strain returns to the 1% small strain stage, G' and G'' can quickly and completely recover to their initial levels, and there is no significant performance degradation after 3 cycles. This proves that CS-BA / PVA hydrogel has excellent self-healing properties and fatigue resistance, and can quickly rebuild the three-dimensional network structure after large deformation.

[0076] Test Example 17 Photothermal performance testing of MIL-101-700@CS-BA / PVA hydrogel and blank hydrogel Experimental steps: One mL of the MIL-101-700@CS-BA / PVA hydrogel prepared in Example 3 and the blank hydrogel prepared in Comparative Example 3 were placed in a 1.5 mL EP tube. An 808 nm near-infrared laser with a power density of 1.0 W was used to irradiate the solution, with the laser spot passing through the center of the liquid. The solution temperature change was recorded every 30 seconds using an infrared thermal imager. After irradiation for 5 minutes, the laser was turned off, and the solution was allowed to cool for 5 minutes. This process was repeated four times, and the temperature rise curve was recorded within 5 minutes. The temperature rise and fall curves of the material, as well as the natural logarithm plot of the temperature change curve of the solution with increasing irradiation time, were plotted based on the recorded temperatures and time points. The photothermal conversion efficiency (η) of the material was calculated using the formula based on the temperature rise and fall curves. The specific calculation formula is as follows:

[0077] Where h is the heat transfer coefficient and S is the sample surface area. The maximum temperature, For ambient temperature, Let I be the heat endothermic in the pure solvent under laser irradiation, I be the laser power, and Aλ be the absorbance of the sample at 808 nm. The results are as follows: Figure 17 a and Figure 17 As shown in b.

[0078] Depend on Figure 17 a and Figure 17 As shown in b, the photothermal stability of MIL-101-700@CS-BA / PVA under intermittent repetitive laser irradiation (808 nm, 1000 mW) indicates that the composite material has good stability. Simultaneously, the photothermal conversion efficiency of the MIL-101-700@CS-BA / PVA composite hydrogel is 44.67%.

[0079] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0080] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. An iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel, comprising a hydrogel matrix and functional nanomaterials in situ composited within the hydrogel matrix, characterized in that, The hydrogel matrix is ​​a reversible double network framework formed by the dynamic covalent cross-linking of phenylboronic acid-modified chitosan CS-BA and polyvinyl alcohol PVA through borate esters, and the functional nanomaterial is MIL-101-700 porous carbon nanoparticles.

2. The iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 1, characterized in that, The MIL-101-700 porous carbon nanoparticles are obtained by high-temperature carbonization of MIL-101.

3. A method for preparing the iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel as described in any one of claims 1-2, characterized in that, Includes the following steps: S1. Reaction of ferric chloride hexahydrate with amino-terephthalic acid yields MIL-101. After high-temperature carbonization, MIL-101 is obtained as MIL-101-700. S2. Dissolve chitosan in solvent A to obtain CS solution. Dissolve 4-carboxyphenylboronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in solvent B to obtain mixture C. Add mixture C to CS solution to react and obtain CS-BA. S3. Mix MIL-101-700 aqueous solution with a concentration of 2 mg / mL, CS-BA aqueous solution with a concentration of 30 mg / mL, and polyvinyl alcohol with a concentration of 100 mg / mL evenly to obtain iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel.

4. The preparation method of the iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 3, characterized in that, In step S1, the molar ratio of ferric chloride hexahydrate to aminoterephthalic acid is 0.7 to 0.9:

1.

5. The method for preparing the iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 3, characterized in that, The high-temperature carbonization temperature mentioned in step S1 is 700℃.

6. The method for preparing iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 3, characterized in that, In step S2, the molar ratio of chitosan, 4-carboxyphenylboronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide is 1:1:1.25:1.

25.

7. The method for preparing iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 3, characterized in that, In step S2, solvent A is a 1% (w / w) aqueous solution of acetic acid, and solvent B is ethanol.

8. The method for preparing the iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 3, characterized in that, The polyvinyl alcohol mentioned in step S3 is type 1799 polyvinyl alcohol.

9. The method for preparing the iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel according to claim 3, characterized in that, In step S3, the volume ratio of MIL-101-700, CS-BA, and polyvinyl alcohol is 2:9:

9.

10. The iron-based MOF-derived carbon-modified CS-BA / PVA hydrogel prepared by any one of claims 3-9 achieves dual antibacterial effects through triple nanoenzyme anti-oxidation and anti-inflammation, and photothermal synergistic Fenton catalysis to generate hydroxyl radicals.

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