CN113144279B - Composite hydrogel for diabetic foot wound dressing, and preparation method and application thereof - Google Patents
Composite hydrogel for diabetic foot wound dressing, and preparation method and application thereof Download PDFInfo
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- CN113144279B CN113144279B CN202110309401.5A CN202110309401A CN113144279B CN 113144279 B CN113144279 B CN 113144279B CN 202110309401 A CN202110309401 A CN 202110309401A CN 113144279 B CN113144279 B CN 113144279B
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- 239000002131 composite material Substances 0.000 title claims abstract description 73
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/38—Esters containing sulfur
- C08F220/387—Esters containing sulfur and containing nitrogen and oxygen
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
- C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
- C08F283/065—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals on to unsaturated polyethers, polyoxymethylenes or polyacetals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
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Abstract
The application provides a composite hydrogel, a preparation method thereof and application of the composite hydrogel in preparation of wound dressings for preventing and treating diabetic foot, the composite hydrogel comprises a zwitterionic polymer and a plant polyphenol compound, wherein the zwitterionic polymer is formed by chemical crosslinking of a zwitterionic monomer, and the plant polyphenol compound and the zwitterionic polymer are physically crosslinked. The preparation method comprises 1) dissolving plant polyphenol compound, zwitterionic monomer, chemical cross-linking agent and initiator in deionized water, and mixing to obtain pre-polymerization solution; (2) removing oxygen from the pre-polymerization liquid; and (3) carrying out free radical polymerization on the pre-polymerization solution under a preset condition to obtain the composite hydrogel. The composite hydrogel has obviously improved tissue adhesiveness, compression performance, plantar decompression performance, oxidation resistance and antibacterial performance. The preparation method is simple and the reaction process is controllable.
Description
Technical Field
The application relates to a composite hydrogel, belonging to the technical field of biomedical materials; in particular to a composite hydrogel for a diabetic foot wound dressing, a preparation method thereof and application thereof in antibiosis, plantar decompression and wound repair.
Background
Diabetes mellitus is a chronic disease, and the incidence rate of diabetes mellitus is increasing worldwide. Diabetic foot ulcers are one of the most serious complications of diabetes, with about 25% of diabetic patients developing diabetic foot ulcers. If the diabetic foot ulcer is not effectively treated, the long-time non-healing of the diabetic foot ulcer can bring amputation risk to a patient when the diabetic foot ulcer is serious, and great influence is brought to the life of the patient. The wound dressing can maintain the moist environment of ulcer parts and release bioactive substances, thereby reducing ulcer infection, accelerating wound healing and playing an important role in treating diabetic foot ulcer. Hydrogel is a common moist wound dressing, and is a water-rich three-dimensional network material constructed by natural polymers or synthetic polymers through covalent bonds or non-covalent bonds. It has the advantages of high water content, good biocompatibility, adjustable structure function, etc.
However, most hydrogel dressings lack an adhesive function, and are difficult to form effective fit with tissues during use, so that the treatment effect is influenced. In addition, when the diabetic foot is in mild condition or in the early stage of the disease process, the sole of the foot is affected by pressure or shearing force during the activity, so that the blood supply is insufficient, the foot is easily infected by bacteria, and the condition of the diabetic foot can aggravate the wound deterioration. Also, diabetic foot ulcers heal slowly due to bacterial infection, inflammatory reactions, and the like. Therefore, the ideal wound dressing hydrogel for treating diabetic foot should have good mechanical property and circulating pressure resistance, can relieve pressure of affected parts, and has the functions of antibiosis, anti-inflammation and healing promotion.
Disclosure of Invention
In order to overcome the defects in the prior art, the inventor of the application prepares a hydrogel material compounded by a plant polyphenol compound and a polyampholyte polymer, the mechanical property and the fatigue resistance of the material are improved by compounding the plant polyphenol compound and the polyampholyte polymer, the tissue adhesion function of the material is improved by utilizing the electrostatic action of hydrogen bonds of the plant polyphenol compound and the polyampholyte polymer, meanwhile, natural polyphenol has good antibacterial and anti-inflammatory effects, the wound healing of diabetic feet is promoted, and finally the hydrogel material suitable for repairing diabetic foot ulcers is obtained and can be expanded to the application in the aspect of treating other pressure injury wounds.
Specifically, the invention provides the composite hydrogel for the diabetic foot wound dressing, and the composite hydrogel has the advantages of wide raw material source, low price, low biotoxicity, controllable polymerization reaction and the like.
One aspect of the present application provides a composite hydrogel for a diabetic foot wound dressing, the composite hydrogel comprising a zwitterionic polymer and a plant-based polyphenol compound, wherein the zwitterionic polymer is formed by chemical crosslinking of a zwitterionic monomer, and the plant-based polyphenol compound is physically crosslinked with the zwitterionic polymer.
Optionally, the tissue adhesion function of the composite hydrogel is provided by a zwitterionic polymer and a plant-based polyphenolic compound.
Optionally, the plant-based polyphenol compound is non-covalently crosslinked to the zwitterionic polymer by hydrogen and/or ionic bonding.
Optionally, the mass content of the plant polyphenol compound in the composite hydrogel is 0.5wt% to 20wt%, preferably 1.5wt% to 8wt%, more preferably 2wt% to 8wt%, and most preferably 6wt% to 8 wt%.
Optionally, the mass content of the plant polyphenol compound in the composite hydrogel is any value or a range value determined by any two values of 0.5wt%, 1.5wt%, 2wt%, 3 wt%, 4 wt%, 6wt%, 8wt% and 20 wt%.
Optionally, the weight content of the zwitterionic monomer structural unit in the zwitterionic polymer in the composite hydrogel is 20wt% to 60wt%, preferably 22wt% to 52 wt%.
Optionally, the zwitterionic monomer building block in the zwitterionic polymer is present in the composite hydrogel at any one or in any two of a 20wt%, 22wt%, 35 wt%, 48 wt%, 50 wt%, 51 wt%, 52wt% and 60wt% by mass.
Optionally, the zwitterionic monomer is a monomer with a double bond and an anionic and cationic group.
Optionally, the zwitterionic monomer is selected from at least one of sulfobetaine methacrylate and 2-methacryloyloxyethyl phosphocholine.
Optionally, the plant polyphenol compound is at least one selected from tannic acid, gallic acid, procyanidins and derivatives thereof.
Another aspect of the present application provides a preparation method of the above composite hydrogel, the preparation method comprising the steps of:
(1) dissolving a plant polyphenol compound, a zwitterionic monomer, a chemical cross-linking agent and an initiator in deionized water, and uniformly mixing to obtain a pre-polymerization solution;
(2) removing oxygen from the pre-polymerization liquid; and
(3) and carrying out free radical polymerization on the pre-polymerization solution under a preset condition to obtain the composite hydrogel.
Optionally, in the step (2), the oxygen is removed by introducing nitrogen into the pre-polymerization solution for 10-60 min.
Optionally, in the step (3), the radical polymerization mode is at least one of temperature-initiated or light-initiated radical polymerization.
Optionally, the plant-based polyphenol compound is contained in the pre-polymerization solution in an amount of 0.5wt% to 20wt%, preferably 1.5wt% to 8wt%, more preferably 2wt% to 8wt%, and most preferably 6wt% to 8 wt%.
Optionally, the plant-based polyphenol compound is contained in the pre-polymerization solution by mass at any value or within a range of any two values selected from 0.5wt%, 1.5wt%, 2wt%, 3 wt%, 4 wt%, 6wt%, 8wt% and 20 wt%.
Optionally, the mass content of the zwitterionic monomer in the pre-polymerization liquid is 20wt% to 60wt%, preferably 22wt% to 52 wt%.
Optionally, the mass content of the zwitterionic monomer in the pre-polymerization liquid is any value or a range of values determined by any two of 20wt%, 22wt%, 35 wt%, 48 wt%, 50 wt%, 51 wt%, 52wt% and 60 wt%.
Optionally, the mass content of the chemical crosslinking agent in the pre-polymerization solution is 0.1 wt% to 0.4 wt%.
Optionally, the chemical crosslinking agent is present in the pre-polymerization solution in an amount of any one or a range of any two of 0.1 wt%, 0.2 wt%, 0.25 wt%, 0.3 wt%, and 0.4 wt%.
Optionally, the mass content of the initiator in the pre-polymerization liquid is 0.04 wt% to 0.2 wt%.
Optionally, the mass content of the initiator in the pre-polymerization liquid is any value or a range of any two values of 0.04 wt%, 0.05 wt%, 0.1 wt% and 0.2 wt%.
Optionally, the zwitterionic monomer is a monomer with a double bond and an anionic and cationic group; preferably, the zwitterionic monomer is selected from at least one of betaine methacrylate sulfonate and 2-methacryloyloxyethyl phosphorylcholine.
Optionally, the plant polyphenol compound is at least one selected from tannic acid, gallic acid, procyanidins and derivatives thereof.
Optionally, the initiator comprises a free radical polymerization initiator.
Optionally, the initiator is selected from at least one of ammonium persulfate, potassium persulfate, and 2-hydroxy-2-methyl-1-phenyl-1-propanone.
Optionally, the chemical crosslinking agent comprises a crosslinking agent with double bonds at the end groups.
Optionally, the chemical crosslinker is selected from at least one of polyethylene glycol diacrylate and N, N' -methylenebisacrylamide.
In a further aspect, the present application provides the use of a composite hydrogel as described above and/or a composite hydrogel prepared according to the above method for the preparation of a wound dressing for the prevention and treatment of diabetic foot.
The beneficial effects that this application can produce include:
1) the preparation method of the composite hydrogel is simple and controllable, free radical polymerization is carried out only by adopting the zwitterion monomer and the plant polyphenol compound in the presence of a small amount of chemical cross-linking agent, the preparation is quick, the cost is low, the industrial production is easy, and the treatment of the diabetic foot ulcer by medical workers can be greatly facilitated.
2) The mechanical property of the composite hydrogel prepared by the method can be regulated and controlled through the relative content of the plant polyphenol compound and the zwitterionic monomer structural unit.
3) The composite hydrogel provided by the application utilizes the plant polyphenol compound and the chemical cross-linking agent to respectively form a physically cross-linked polymer network and a chemically cross-linked polymer network. The plant polyphenol compound-zwitter ion polymer composite hydrogel maintains a network structure through chemical crosslinking and a large number of hydrogen bonds, ion-dipole effects and dipole-dipole effects. The prepared composite hydrogel has the synergistic effect of non-covalent crosslinking and covalent crosslinking, and the synergistic effect ensures that the composite hydrogel has excellent tissue adhesiveness, can be directly and tightly adhered to wounds and prevents external infection.
4) The composite hydrogel prepared by the application has excellent compression resistance and fatigue resistance, and shows stable compression strength in a multi-cycle compression experiment, so that the pressure of an affected part can be reduced when the composite hydrogel is applied to a sole as a diabetic foot wound dressing, the dressing change times are reduced, secondary damage to tissues is avoided when dressing change is carried out, pain is reduced, and the medical cost is saved.
5) The plant polyphenol is crosslinked with the zwitterionic polymer through non-covalent action, and due to the antibacterial property and the antioxidant property of the plant polyphenol and the stain resistance of the zwitterionic polymer, the composite hydrogel disclosed by the application is used for resisting gram-positive bacteria (such as: staphylococcus aureus), etc., and has a certain inhibiting effect on infection and inflammatory reaction of diabetic foot ulcer.
Drawings
Fig. 1 is a schematic diagram of the synthesis of hydrogels according to examples 1 to 3 of the present application.
Figure 2a shows the compression performance curves of the hydrogels according to examples 1 to 3 of the present application.
Figure 2b shows the compression performance curve of the hydrogel according to example 1 of the present application after cycling.
FIG. 2c is an enlarged view of the compression performance curve of the hydrogel of FIG. 2b after 1 to 5 cycles.
FIG. 2d is an enlarged view of the compression performance curve of the hydrogel of FIG. 2b after 2995 to 3000 cycles of its use.
Fig. 3a shows a schematic diagram of a plantar pressure reduction experiment.
Figure 3b shows the plantar pressure reduction properties of the composite hydrogel of example 1 of the present application.
Fig. 4 shows the tissue surface adhesion performance curves of the hydrogels according to examples 1 to 3 and comparative example 1 of the present application.
Fig. 5 shows the antioxidant properties of the hydrogels according to examples 1 to 3 and comparative example 1 of the present application.
Fig. 6 shows a graph illustrating the antibacterial results of the hydrogels according to examples 1 to 3 of the present application and comparative example.
Fig. 7 shows a schematic diagram of the effect of the wound dressings made of hydrogel according to example 1 of the present application and comparative example in promoting wound healing in diabetic mice.
Detailed Description
The present application will be described in detail with reference to examples, but the present application is not limited to these examples.
The endpoints of the ranges and any values disclosed in the present application are not limited to the precise range or value, and such ranges or values should be understood to include proximity to such ranges or values. For numerical ranges, the endpoints of each of the ranges and the individual points between each may be combined with each other to give one or more new numerical ranges, and these numerical ranges should be considered as specifically disclosed herein.
Unless otherwise specified, the raw materials (e.g., zwitterionic monomer, plant-based polyphenol compound, chemical crosslinking agent, initiator, etc.) in the examples of the present application were all purchased commercially.
The test devices used in the examples of the present application are all devices commonly used in the art, unless otherwise specified.
Example 1
3.7g of Tannic acid (Tannic acid), 22.3g of [2- (methacryloyloxy) ethyl]Dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA, i.e. sulfobetaine methacrylate), 90mg polyethylene glycol diacrylate (PEGDA, M)W700), 23mg ammonium persulfate (i.e., APS) was added to 20mL deionized water to obtain a pre-polymerization solution. And introducing nitrogen into the prepolymer solution for 30min to remove oxygen, injecting the deoxidized prepolymer solution into a closed glass mold, putting the closed glass mold into a water bath tank at 60 ℃ overnight, and preparing the hydrogel by thermal initiation of free radical polymerization (as shown in figure 1). The hydrogel prepared in this example was designated T8S 4.
Example 2
Mixing 1.8g tannic acid, 22.3g SBMA, 90mg PEGDA (M)W700), 23mg ammonium persulfate was added to 20mL deionized water to obtain a prepolymerization solution. And introducing nitrogen into the prepolymer solution for 30min to remove oxygen, injecting the deoxidized prepolymer solution into a closed glass mold, putting the closed glass mold into a water bath tank at 60 ℃ overnight, and preparing the hydrogel by thermal initiation of free radical polymerization (as shown in figure 1). The hydrogel prepared in this example was designated T4S 4.
Example 3
Mixing 0.9g tannic acid, 22.3g SBMA, 90mg PEGDA (M)W700), 23mg ammonium persulfate was added to 20mL deionized water to obtain a prepolymerization solution. And introducing nitrogen into the prepolymer solution for 30min to remove oxygen, injecting the deoxidized prepolymer solution into a closed glass mold, putting the closed glass mold into a water bath tank at 60 ℃ overnight, and preparing the hydrogel by thermal initiation of free radical polymerization (as shown in figure 1). The hydrogel prepared in this example was designated T2S 4.
Example 4
0.4g of Gallic acid (Gallic acid), 5.9g of 2-Methacryloyloxyethyl phosphorylcholine (2-Methacryloyloxyethyl phosphorylcholine), 82mg of N, N' -methylenebisacrylamide, and 27mg of potassium persulfate (i.e., KPS) were added to 20mL of deionized water to obtain a prepolymerization solution. And introducing nitrogen into the prepolymerization liquid for 30min to remove oxygen, injecting the deoxidized prepolymerization liquid into a closed glass mold, putting the closed glass mold into a water bath tank at 60 ℃ overnight, and preparing the hydrogel by thermal initiation of free radical polymerization. The hydrogel prepared in this example was designated G8M 1.
Example 5
1g of procyanidins (Proanthocyanidins), 11.8g of 2-methacryloyloxyethyl phosphorylcholine, 82mg of N, N' -methylenebisacrylamide, and 16.5mg of 2-hydroxy-2-methyl-1-phenyl-1-propanone were added to 20mL of deionized water to obtain a pre-polymerization solution. Introducing nitrogen into the prepolymer solution for 30min to remove oxygen, injecting the deoxidized prepolymer solution into a closed glass mold, irradiating for 30min under the ultraviolet light with the wavelength of 365nm, and preparing the hydrogel by photo-initiated free radical polymerization. The hydrogel prepared in this example was designated P8M 2.
Comparative example 1
22.3g of SBMA, 90mg of PEGDA (M)W700), 23mg ammonium persulfate was added to 20mL deionized water to obtain a prepolymerization solution. And introducing nitrogen into the prepolymerization liquid for 30min to remove oxygen, injecting the deoxidized prepolymerization liquid into a closed glass mold, putting the closed glass mold into a water bath tank at 60 ℃ overnight, and preparing the hydrogel by thermal initiation of free radical polymerization. The hydrogel prepared in this example was designated as S4.
Example 6
And (3) testing the compression performance: the hydrogels of examples 1 to 5 were prepared as disc-shaped samples of 10mm diameter and 2mm thickness and subjected to a single compression at a compression rate of 10% strain/min to a sample compression of 90% strain. The compression properties of the hydrogels prepared in examples 1-3 are shown in FIG. 2 a.
As can be seen from FIG. 2a, under the same strain conditions, the incorporation of tannic acid improves the compression resistance of the composite hydrogel, and the higher the content of tannic acid in the composite hydrogel, the greater the required compressive stress. This indicates that the compressive resistance of the composite hydrogel is stronger as the content of tannic acid in the composite hydrogel increases. Particularly when the mass ratio of tannic acid to the pre-polymerized liquid was 8wt% (i.e., example 1), the composite hydrogel exhibited excellent compression resistance.
Specifically, under the same test conditions, the compressive strength (i.e., compressive stress) of example 1 was 20MPa, the compressive strength of example 2 was 11MPa, the compressive strength of example 3 was 7MPa, the compressive strength of example 4 was 8MPa, and the compressive strength of example 5 was 13 MPa.
Additionally, the hydrogel of example 1 was subjected to 3000 compression cycles to 60% strain, and the results are shown in figure 2b, using the same conditions.
As can be seen from fig. 2b, when the hydrogel was compressed 3000 times, the hydrogel exhibited excellent cycle compressibility and excellent recovery properties.
FIG. 2c is an enlarged view of the compression performance curve of the hydrogel of FIG. 2b after 1 to 5 cycles of cycling, showing the excellent cycling compression performance and excellent recovery performance of the hydrogel of example 1 after 1 to 5 cycles of cycling.
Figure 2d is an enlarged view of the compression performance curve of the hydrogel of figure 2b after 2995 to 3000 cycles of hydrogel cycling, showing excellent cycling compression performance and excellent recovery performance of the hydrogel of example 1 after 2995 to 3000 cycles of cycling.
Example 7
Testing plantar pressure: plantar pressure was tested by placing a thin film pressure sensor (20 mm diameter) over the hydrogel of example 1 as shown in fig. 3a, and standing an adult male weighing approximately 65 kg on top, with the hydrogel and thin film sensor in the third metatarsophalangeal joint (plantar a in fig. 3 a) or lateral heel (plantar B in fig. 3). The control group was the pressure on the same position of the sole of the foot when tested in the absence of hydrogel. The pressure curve of the collected sensor signal values is shown in FIG. 3b, and the pressure at the part A, B of the sole of the foot when the test subject stands normally is measured to be 61.4kPa (corresponding to the point a on FIG. 3 b)0) And 84.8kPa (corresponding to point b on FIG. 3 b)0) After the hydrogel is placed on the sole, the pressure at A, B position of the sole is reduced to 47.6kPa (corresponding to point a on fig. 3 b)1) And 54.7kPa (corresponding to point b on FIG. 3 b)1). Therefore, the hydrogel can obviously reduce the pressure of the sole and is beneficial to the repair of the sole wound.
Although not shown in the figure, the hydrogels prepared in examples 2 to 5 can also significantly reduce the pressure on the sole of foot, and facilitate the repair of wounds on the sole of foot.
Example 8
Tissue surface adhesion performance test: fresh pigskin was cut into 40mm × 15mm × 3mm strips, the hydrogel samples (15mm × 15mm × 2mm) of examples 1 to 5 and comparative example 1 were attached between two pigskins, respectively, and a 100g weight was placed on the pigskin-hydrogel-pigskin and held for 5 minutes. The end of the pigskin was clamped using a universal tester jig and stretched at a speed of 50mm/min until the bonded portion was completely peeled off. Interfacial bond strength is the maximum load divided by the bond area. The adhesion properties of the hydrogels prepared in examples 1 to 3 and comparative example 1 were measured as shown in FIG. 4.
As can be seen from fig. 4, the introduction of tannic acid significantly improves the interfacial adhesion strength of the composite hydrogel, i.e., improves the tissue adhesion of the composite hydrogel. And as the content of tannic acid is higher, the interface adhesive strength is larger. Thus, it was demonstrated that the tissue adhesion of the composite hydrogel became stronger as the content of tannic acid in the composite hydrogel increased. Particularly when the mass ratio of tannic acid to the pre-polymerization solution was 8wt% (i.e., example 1), the composite hydrogel exhibited excellent tissue adhesion. The composite hydrogels prepared in examples 2 to 3 also exhibited excellent tissue adhesion.
Using the same test method, examples 4 and 5 were also subjected to the tissue surface adhesion property test, and the composite hydrogels prepared in examples 4 and 5 also exhibited excellent tissue adhesion.
Specifically, under the same test conditions, the interfacial adhesion strength of example 1 was 20kPa, the interfacial adhesion strength of example 2 was 12kPa, the interfacial adhesion strength of example 3 was 6kPa, the interfacial adhesion strength of example 4 was 7kPa, the interfacial adhesion strength of example 5 was 11kPa, and the interfacial adhesion strength of comparative example 1 was 1.4 kPa.
Example 9
Oxidation resistance: 100mg of the hydrogel sample was placed in 3ml of 0.1 mM 1, 1-diphenyl-2-trinitrophenylhydrazine (DPPH) solution, reacted at room temperature for 30min in the dark, the absorbance of the solution at 517nm was measured using an ultraviolet spectrophotometer, and the DPPH radical scavenging rate was calculated: DPPH clearance ═ Ablank-Asample)/Ablank X 100% where AblankIs the absorbance, A, of a DPPH solution before reaction with the hydrogelsampleIs the absorbance of the mixture of DPPH solution and hydrogel after reaction for 30 min.
The measured antioxidant properties of the hydrogels prepared in examples 1 to 3 and comparative example 1 are shown in fig. 5. As can be seen from fig. 5, the introduction of tannic acid significantly improves the radical scavenging activity of the composite hydrogel, i.e., improves the oxidation resistance of the composite hydrogel. As the content of tannic acid increases, its oxidation resistance increases. When the mass ratio of tannic acid to the pre-polymerization solution was 8wt% (i.e., example 1), the DPPH radical scavenging rate was 38% for 100mg of the composite hydrogel, and the hydrogel prepared in comparative example 1 had no DPPH radical scavenging activity.
In example 2, the DPPH radical scavenging rate of 100mg of the composite hydrogel was 17%; in example 3, 100mg of the composite hydrogel had a DPPH radical scavenging rate of 11%.
Although not shown, the hydrogels prepared in examples 4 and 5 also had excellent antioxidant properties. The same test methods as in examples 1 to 3. In example 4, the DPPH radical scavenging rate of 100mg of the composite hydrogel was 6%, and in example 5, the DPPH radical scavenging rate of 100mg of the composite hydrogel was 15%.
From the above data, it can be seen that the composite hydrogels prepared in examples 1 to 5 have excellent oxidation resistance.
Example 10
Antibacterial property: the overnight cultured staphylococcus aureus solution was diluted 1000-fold with tryptone soy broth. 100 mu L of the bacterial liquid is evenly coated on an agar culture medium, cylindrical hydrogel samples with the diameter of 9mm and the thickness of 3mm in the examples 1 to 5 and the comparative example 1 are respectively placed on the surfaces of the culture medium, the agar culture plates with the patches are placed in a constant temperature incubator at 37 ℃ for 18 hours, and the diameter of the inhibition zone around the hydrogel samples is measured and compared. As can be seen from fig. 6, the composite hydrogels prepared in examples 1 to 3 of the present application have excellent antibacterial effects.
Specifically, the hydrogel of comparative example 1 had a zone of inhibition of almost 0 diameter, the hydrogel of example 1 had a zone of inhibition of 27.9mm diameter, the hydrogel of example 2 had a zone of inhibition of 22.4mm diameter, the hydrogel of example 3 had a zone of inhibition of 20.2mm diameter, the hydrogel of example 4 had a zone of inhibition of 15.1mm diameter, and the hydrogel of example 5 had a zone of inhibition of 18.3mm diameter.
Example 11
Diabetic animal wound healing test: the full-thickness skin defect model of diabetic mice was used to evaluate the wound healing promoting properties of the hydrogels of example 1 and comparative example 1 in animals. Briefly, a wound of 10mm in diameter was formed on the back skin of diabetic mice using a punch. Wound dressings (10 mm in diameter and 1mm in thickness) made of hydrogels according to example 1 and comparative example 1 were placed on the skin defect sites, and the skin defect sites of the control mice were not treated. Photographs of wound sites were taken and recorded on days 0, 2, 4, 7, 14 and 21, respectively (corresponding to D0, D2, D4, D7, D14, D21, respectively). As can be seen from fig. 7, the skin wound of the mouse covered with the hydrogel group of example 1 healed faster than the wounds of the mouse covered with the hydrogel group of comparative example 1 and the mouse without the treatment group, indicating that the composite hydrogel prepared in example 1 has a better diabetic wound repair function as a wound dressing.
Although not shown in the figure, the wound dressings prepared from the composite hydrogels prepared in examples 2 to 5 also have a good diabetic wound repair function.
Although the present application has been described with reference to a few embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the application as defined by the appended claims.
Claims (20)
1. A composite hydrogel for a diabetic foot wound dressing, which is characterized by consisting of a zwitterionic polymer and a plant polyphenol compound, wherein the zwitterionic polymer is formed by free radical polymerization crosslinking of a zwitterionic monomer under the action of a chemical crosslinking agent and an initiator, and the plant polyphenol compound is physically crosslinked with the zwitterionic polymer;
the plant polyphenol compound and the zwitterionic polymer are subjected to non-covalent crosslinking through hydrogen bonds and/or ionic bonds;
the mass content of the plant polyphenol compound in the composite hydrogel is 0.5-20 wt%.
2. The composite hydrogel according to claim 1, wherein the mass content of the plant polyphenol compound in the composite hydrogel is 1.5wt% to 8 wt%.
3. The composite hydrogel according to claim 1, wherein the mass content of the plant polyphenol compound in the composite hydrogel is 2wt% to 8 wt%.
4. The composite hydrogel according to claim 1, wherein the mass content of the plant polyphenol compound in the composite hydrogel is 6wt% to 8 wt%.
5. The composite hydrogel according to claim 1, wherein the mass content of the zwitterionic monomer structural units in the zwitterionic polymer in the composite hydrogel is 20-60 wt%.
6. The composite hydrogel according to claim 1, wherein the mass content of the zwitterionic monomer structural units in the zwitterionic polymer in the composite hydrogel is 22-52 wt%.
7. The composite hydrogel according to claim 1,
the zwitterionic monomer is a monomer with double bonds and anionic and cationic groups; and/or
The plant polyphenol compound is at least one selected from tannic acid, gallic acid, procyanidin and its derivatives.
8. The composite hydrogel according to claim 7, wherein the zwitterionic monomer is selected from at least one of betaine methacrylate sulfonate and 2-methacryloyloxyethyl phosphorylcholine.
9. A method for preparing the composite hydrogel according to any one of claims 1 to 8, wherein the method comprises the following steps:
(1) dissolving a plant polyphenol compound, a zwitterionic monomer, a chemical cross-linking agent and an initiator in deionized water, and uniformly mixing to obtain a pre-polymerization solution;
(2) removing oxygen from the pre-polymerization liquid; and
(3) and carrying out free radical polymerization on the pre-polymerization solution under a preset condition to obtain the composite hydrogel.
10. The production method according to claim 9,
the mass content of the plant polyphenol compound in the pre-polymerization solution is 0.5-20 wt%;
the mass content of the zwitterionic monomer in the pre-polymerization liquid is 20-60 wt%.
11. The preparation method of claim 10, wherein the mass content of the plant polyphenol compound in the pre-polymerization solution is 1.5wt% to 8 wt%.
12. The preparation method of claim 10, wherein the mass content of the plant polyphenol compound in the pre-polymerization solution is 2wt% to 8 wt%.
13. The preparation method of claim 10, wherein the mass content of the plant polyphenol compound in the pre-polymerization solution is 6wt% to 8 wt%.
14. The preparation method of claim 10, wherein the mass content of the zwitterionic monomer in the pre-polymerization solution is 22-52 wt%.
15. The production method according to claim 9,
the zwitterionic monomer is a monomer with double bonds and anionic and cationic groups; and/or
The plant polyphenol compound is at least one selected from tannic acid, gallic acid, procyanidin and its derivatives.
16. The method of claim 15, wherein the zwitterionic monomer is selected from at least one of betaine methacrylate sulfonate and 2-methacryloyloxyethyl phosphorylcholine.
17. The production method according to claim 9,
the initiator comprises a free radical polymerization initiator;
the chemical crosslinking agent comprises a crosslinking agent with double bonds at the end group.
18. The production method according to claim 17, wherein the initiator is at least one selected from the group consisting of ammonium persulfate, potassium persulfate, and 2-hydroxy-2-methyl-1-phenyl-1-propanone.
19. The method of claim 17, wherein the chemical cross-linking agent is at least one selected from the group consisting of polyethylene glycol diacrylate and N, N' -methylenebisacrylamide.
20. Use of a composite hydrogel according to any one of claims 1 to 8, and/or a composite hydrogel prepared according to the method of any one of claims 9 to 19, in the preparation of a wound dressing for the prevention and treatment of diabetic foot.
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