CN111773429A - Hydrogel dressing and preparation method thereof, multifunctional nano composite dressing and preparation method and application thereof - Google Patents
Hydrogel dressing and preparation method thereof, multifunctional nano composite dressing and preparation method and application thereof Download PDFInfo
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- 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
- A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- 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
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- 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
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- 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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- A—HUMAN NECESSITIES
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Abstract
The invention relates to a hydrogel dressing and a preparation method thereof, a multifunctional nano composite dressing and a preparation method and application thereof, and relates to the technical field of medical dressings. The gel dressing solves the technical problems that the existing gel dressing is single in functionality, difficult to cover the whole period of wound repair, weak in antibacterial performance and difficult to achieve satisfactory effect. The multifunctional hydrogel dressing is constructed by utilizing the modified chitosan and the functionalized polyethylene glycol, has good biocompatibility, anti-inflammation, proper skin adhesion and certain hemostatic performance, and can meet various complex clinical requirements. The invention carries photo-thermal nano material and antibacterial drug in the hydrogel dressing network structure, thereby providing a multifunctional nano composite dressing and improving the antibacterial property of the dressing. The multifunctional nano composite dressing can play an obvious role in promoting both the treatment period and the prognosis period in the healing process of the bacterial infection wound, and makes up the defects of the current commercial dressing.
Description
Technical Field
The invention relates to the technical field of medical dressings, in particular to a hydrogel dressing and a preparation method thereof, a multifunctional nano composite dressing and a preparation method and application thereof.
Background
The skin is a natural physiological barrier for resisting the external environment of the organism, and can effectively prevent tissue dehydration and microorganism invasion. But at the same time the nature of the skin also makes it susceptible to various degrees of damage. Surgical wounds and bacterial infections of wounds have become common medical problems at present. Repair of skin wounds generally goes through 4 typical phases: a haemostatic phase, an inflammatory phase, a cell proliferation phase and a tissue remodeling phase.
The traditional approach to treating bacterial-infected wounds is to use antibiotics, however, the long-term use of antibiotics may induce bacterial resistance, which undoubtedly aggravates the patient's condition and increases the difficulty of treatment. Currently, many nanomaterials are reported to be applied to antibacterial therapy. Photosensitive materials such as graphene quantum dots and cerium dioxide nanoparticles can generate Reactive Oxygen Species (ROS) under the irradiation of an external light source, and the ROS and adjacent biological macromolecules generate oxidation reaction to generate cytotoxicity effect, so that bacterial cells are damaged and even die. The method utilizes nano materials with high photothermal conversion rate, such as gold nano materials, carbon-based nano materials and the like, to generate a large amount of heat under the irradiation of an external light source to cause bacterial lysis.
The existing methods for treating bacterial infections, such as photodynamic therapy and photothermal therapy, which replace antibiotics, also have some disadvantages: although ROS generated by the photosensitive material can kill bacteria efficiently, due to the characteristics of short service life (less than 200ns), short transmission distance (about 20nm) and the like of ROS, the ROS can only play a role in a limited range, and further application of the ROS is limited; high heat generated by the high-concentration photo-thermal material can cause unnecessary damage to normal skin tissues, and the low-concentration photo-thermal material can not achieve good sterilization effect due to the initiation of a heat shock protein protection mechanism; in addition, the large amount of free radicals generated by photodynamic and photothermal therapy is also not beneficial to the healing of the wound surface after the treatment.
The wound dressing can replace the barrier function of damaged skin, is attached to the surface of a wound, can effectively reduce secondary damage, optimizes cell regeneration and migration, and prevents infection. At present, the wound dressing mainly comprises gauze, synthetic fiber dressing, foaming polymer dressing, hydrogel dressing and the like. The hydrogel dressing has the characteristics of high water content, water absorption, flexibility and the like, so the hydrogel dressing has an application prospect. However, the current commercial dressing generally has single performance and poor antibacterial effect, can only play a role in simply protecting the wound, and is difficult to meet the actual complex treatment requirement.
Disclosure of Invention
The invention provides a hydrogel dressing, a preparation method thereof, a multifunctional nano composite dressing, a preparation method and application thereof, and aims to solve the technical problems that gel dressings used in the prior art are generally single in functionality, difficult to cover the whole period of wound repair, weak in antibacterial performance and difficult to achieve satisfactory effects.
In order to solve the technical problems, the technical scheme of the invention is as follows:
the invention provides a hydrogel dressing, which is hydrogel with a reticular structure obtained by covalent crosslinking of aldehyde-functionalized polyethylene glycol and alkylated chitosan;
the alkylated chitosan has the following structural formula:
the aldehyde group functionalized polyethylene glycol has the following structural formula:
in the above technical solution, preferably, the aldehyde-functionalized polyethylene glycol is prepared by the following method:
0.5g of 4-aldehyde benzoic acid, 1.6g of PEG 2000 and 0.025g of 4-dimethylaminopyridine were dissolved in 50mL of tetrahydrofuran, 0.84g of dicyclohexylcarbodiimide was added, and the reaction was stirred at room temperature overnight; filtering off the resulting white solid; the filtrate is purified for 3 times by dissolving with tetrahydrofuran and then adding ether for precipitation to prepare the aldehyde group functionalized polyethylene glycol.
In the above technical solution, preferably, the alkylated chitosan is prepared by the following method:
1g of chitosan is firstly dissolved in 50mL of 0.2M acetic acid solution, and then 40mL of ethanol is added; adjusting the pH value of the solution to 5.1, then adding 0.01eq of dodecanal with the mole number of chitosan amino groups, reacting for 20min, and introducing excessive sodium cyanoborohydride to reduce generated imine bonds; after continuing to react for 18h, adding 50mL of ethanol to precipitate the generated alkylated chitosan, and centrifuging to obtain a precipitate; washing the precipitate with ethanol for 3 times to obtain final product alkylated chitosan.
The invention also provides a preparation method of the hydrogel dressing, which comprises the following steps:
mixing an alkylated chitosan (FCS) acetic acid aqueous solution with an aldehyde group functionalized polyethylene glycol aqueous solution, and carrying out a rapid crosslinking reaction under the condition of shaking at room temperature to prepare the hydrogel dressing.
In the above technical solution, it is preferable that the mass fraction of the alkylated chitosan (FCS) acetic acid aqueous solution is 3% and the mass fraction of the aldehyde-functionalized polyethylene glycol aqueous solution is 20%.
The invention also provides a multifunctional nano composite dressing, which is obtained by carrying photo-thermal nano materials and antibacterial drugs in the reticular structure of the hydrogel dressing.
In the above technical solution, preferably, the antibacterial agent is supported on the photothermal nanomaterial.
In the above technical solution, preferably, the photothermal nanomaterial is WS2Nanosheets, the antibacterial agent being ciprofloxacin.
The invention also provides a preparation method of the multifunctional nano composite dressing, which comprises the following steps:
Dispersing the antibacterial drug and the photo-thermal nano material in deionized water, co-incubating in a rotary mixer, and then removing the unadsorbed antibacterial drug by centrifugation and deionized water washing to obtain the photo-thermal nano material loaded with the antibacterial drug;
Preparing an acetic acid solution of alkylated chitosan and an aqueous solution of aldehyde-functionalized polyethylene glycol, respectively;
the photo-thermal nano material loaded with the antibacterial drug is mixed with acetic acid solution of alkylated chitosan, aqueous solution of aldehyde group functionalized polyethylene glycol is added, and the mixture is uniformly mixed on a vortex oscillator to prepare the multifunctional nano composite dressing.
The invention also provides application of the multifunctional nano composite dressing in bacterial infection wound healing.
The invention has the beneficial effects that:
the multifunctional hydrogel dressing is constructed by utilizing the modified chitosan and the functionalized polyethylene glycol, has good biocompatibility, anti-inflammation, proper skin adhesion and certain hemostatic performance, and can meet various complex clinical requirements. The method comprises the following specific steps:
1. the function covers 4 stages of wound healing, and the defect of single function of the traditional dressing is overcome.
2. Has good antibacterial performance, and makes up the defect of poor antibacterial effect of the traditional dressing.
3. Takes account of the antibacterial function and the function of promoting wound surface prognosis.
The invention carries photo-thermal nano material and antibacterial drug in the hydrogel dressing network structure, thereby providing a multifunctional nano composite dressing and improving the antibacterial property of the dressing. The multifunctional nano composite dressing can play an obvious role in promoting both the treatment period and the prognosis period in the healing process of the bacterial infection wound, and makes up the defects of the current commercial dressing.
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The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
FIG. 1 is a scheme showing the synthesis of alkylated chitosans and aldehyde-functionalized polyethylene glycols.
Fig. 2 is a graph of gel forming and mechanical property analysis of the synthetic hydrogel dressing of example 1, in which: (a) the gel forming performance test chart is shown, and the mechanical property rheological analysis chart is shown in the (b).
Fig. 3 is a graph depicting antioxidant, tissue adhesive, self-healing, and hemostatic properties of the synthetic hydrogel dressing of example 1, wherein: (a) the anti-oxidation and anti-inflammatory performance diagram, (b) the tissue adhesion diagram, (c) the self-healing and performance diagram, and (d) the hemostatic performance diagram.
Fig. 4 is a graph of the cytotoxicity, biocompatibility performance test of the synthesized hydrogel dressing of example 1, in which: (a) is a cytotoxicity map, and (b) is a blood cell biocompatibility map.
FIG. 5 shows the photothermal nanomaterials WS synthesized in example 22A representation of nanoplatelets, wherein: (a) the transmission electron microscope picture of the photo-thermal nano material tungsten disulfide nano sheet, (b) the XPS spectrum of the tungsten disulfide nano sheet, (c) the nano material with different concentrations is in 0.5w/cm2Photo-thermal property diagram under illumination intensity, (d) is photo-thermal nano material WS2Thermal stability test chart of (1).
Fig. 6 is a graph representing the photo-responsive therapeutic performance of the multifunctional nanocomposite dressing synthesized in example 2, in which: (a) the photo-response drug release curve, (b) the photo-thermal property diagram, and (c) the synergistic antibacterial action diagram.
Fig. 7 is a graph showing the in vivo antibacterial effect and the wound healing promotion performance of the multifunctional nanocomposite dressing synthesized in example 2.
FIG. 8 is a nuclear magnetic hydrogen spectrum of the aldehyde-functionalized polyethylene glycol synthesized in example 1.
FIG. 9 is a graph of the infrared contrast of alkylated chitosan and chitosan synthesized in example 1.
Fig. 10 is a scanning electron microscope image of the multifunctional nanocomposite dressing synthesized in example 2.
Detailed Description
The invention idea of the invention is as follows: the treatment of wounds infected by bacteria is a common medical problem, and the current commercial dressing generally has single performance and poor antibacterial effect, can only play a role in simply protecting the wounds and is difficult to meet the actual complex treatment needs. Therefore, the multifunctional hydrogel dressing is constructed by utilizing the modified chitosan and the functionalized polyethylene glycol, has good biocompatibility, anti-inflammation, proper skin adhesion and certain hemostasis performance, and can adapt to various complex clinical requirements; meanwhile, the multifunctional nano composite dressing is obtained by carrying the photo-thermal nano material and the antibacterial drug in the hydrogel network structure, and the antibacterial performance of the dressing is improved. The nano composite dressing can play an obvious role in promoting both the treatment period and the prognosis period in the healing process of the bacterial infection wound, and makes up the defects of the current commercial dressing.
The Schiff base type hydrogel has self-repairing property, so that the applicability of the gel can be enhanced, and the service life of the gel can be prolonged, and therefore, the Schiff base type hydrogel has important research value in hydrogel type dressings. Chitosan is a green renewable material, has good biocompatibility and antibacterial property and the performance of promoting wound healing, and is widely applied to the field of biological medicine. At present, chitosan-based schiff base hydrogel is generally obtained by covalently crosslinking a micromolecular aldehyde compound and chitosan molecules, but the further application of the micromolecular aldehyde is limited due to higher biotoxicity of the micromolecular aldehyde. In order to reduce the biological toxicity, the invention uses the aldehyde group functionalized polyethylene glycol molecule to replace micromolecular aldehyde to be crosslinked with the modified chitosan to obtain the novel hydrogel with excellent performance.
The invention provides a hydrogel dressing, which is hydrogel with a reticular structure obtained by covalent crosslinking of aldehyde-functionalized polyethylene glycol and alkylated chitosan;
the alkylated chitosan has the following structural formula:
the aldehyde group functionalized polyethylene glycol has the following structural formula:
the invention also provides a method for synthesizing the hydrogel dressing, which comprises the following steps:
as shown in figure 1, through the formation of imine bonds and reduction reaction, dodecyl groups with a fixed proportion can be modified on a chitosan polymer chain, a certain membrane insertion performance is given to the dodecyl groups, and the formation of imine bonds and reduction reaction are beneficial to improving the tissue adhesion and the hemostatic performance of the hydrogel material obtained by crosslinking. The aromatic aldehyde functionalized polyethylene glycol chain (PEG) can improve the covalent bond stability of the formed Schiff base and improve the biocompatibility. Mixing 3% of alkylated chitosan (FCS) acetic acid aqueous solution and 20% of aldehyde group functionalized polyethylene glycol aqueous solution in proportion, and performing rapid crosslinking reaction under the condition of shaking at room temperature to prepare the hydrogel dressing (HG). The method specifically comprises the following steps:
1. the aldehyde group functionalized polyethylene glycol is prepared by the following method:
0.5g of 4-aldehyde benzoic acid, 1.6g of PEG 2000 and 0.025g of 4-dimethylaminopyridine were dissolved in 50mL of tetrahydrofuran, 0.84g of dicyclohexylcarbodiimide was added, and the reaction was stirred at room temperature overnight; filtering off the resulting white solid; the filtrate is purified for 3 times by dissolving with tetrahydrofuran and then adding ether for precipitation to prepare the aldehyde group functionalized polyethylene glycol.
2. The alkylated chitosan is prepared by the following method:
1g of chitosan is firstly dissolved in 50mL of 0.2M acetic acid solution, and then 40mL of ethanol is added; adjusting the pH value of the solution to 5.1, then adding 0.01eq of dodecanal with the mole number of chitosan amino groups, reacting for 20min, and introducing excessive sodium cyanoborohydride to reduce generated imine bonds; after continuing to react for 18h, adding 50mL of ethanol to precipitate the generated alkylated chitosan, and centrifuging to obtain a precipitate; washing the precipitate with ethanol for 3 times to obtain final product alkylated chitosan.
3. Mixing 3% of alkylated chitosan (FCS) acetic acid aqueous solution and 20% of aldehyde group functionalized polyethylene glycol aqueous solution, and performing rapid crosslinking reaction under the condition of shaking at room temperature to prepare the hydrogel dressing (HG).
The invention also provides a multifunctional nano composite dressing, which is obtained by carrying photo-thermal nano materials and antibacterial drugs in the reticular structure of the hydrogel dressing. Preferably, the antibacterial agent is supported on the photothermal nanomaterial. Preferably, the photothermal nanomaterial is WS2Nanosheets, the antibacterial agent being ciprofloxacin.
The invention also provides a preparation method of the multifunctional nano composite dressing, which comprises the following steps:
Dispersing the antibacterial drug and the photo-thermal nano material in deionized water, co-incubating in a rotary mixer, and then removing the unadsorbed antibacterial drug by centrifugation and deionized water washing to obtain the photo-thermal nano material loaded with the antibacterial drug;
Preparing an acetic acid solution of alkylated chitosan and an aqueous solution of aldehyde-functionalized polyethylene glycol, respectively;
the photo-thermal nano material loaded with the antibacterial drug is mixed with acetic acid solution of alkylated chitosan, aqueous solution of aldehyde group functionalized polyethylene glycol is added, and the mixture is uniformly mixed on a vortex oscillator to prepare the multifunctional nano composite dressing.
The invention also provides application of the multifunctional nano composite dressing in bacterial infection wound healing.
Example 1 Synthesis and Performance characterization of hydrogel dressings
(1) Synthesis of hydrogel dressings
4-Aldobenzoic acid (0.5g), PEG 2000(1.6g) and 4-dimethylaminopyridine (0.025g) were dissolved in 50mL of tetrahydrofuran, dicyclohexylcarbodiimide (0.84g) was added, and the reaction was stirred at room temperature overnight. The resulting white solid was filtered off. The filtrate was purified 3 times by dissolving in an appropriate amount of tetrahydrofuran and precipitating with diethyl ether. The nuclear magnetic hydrogen spectrum is shown in FIG. 8.
1H NMR(500MHz,CDCl3,):10.11(s,2H),8.22(d,J＝8.3Hz,4H),7.95(d,J＝8.3Hz,4H),4.53-4.50(m,4H),3.86-3.84(m,4H),3.70-3.60(m,172-176H).
1g of chitosan was dissolved in 50mL of 0.2M acetic acid solution, and 40mL of ethanol was added. Adjusting the pH value of the solution to 5.1, then adding 0.01eq of dodecanal with the mole number of chitosan amino groups, reacting for 20min, and introducing excessive sodium cyanoborohydride to reduce the generated imine bond. After further reaction for 18h, the resulting alkylated chitosan was precipitated by adding 50mL of ethanol and centrifuged to obtain a precipitate. The precipitate was washed 3 times with ethanol to give the final product. The infrared spectrum is shown in FIG. 9.
Preparing an acetic acid solution of alkylated chitosan with a mass fraction of 3% (the concentration of acetic acid is 0.2M) and an aqueous solution of aldehyde-functionalized PEG with a mass fraction of 20%, respectively;
0.3g of the alkylated chitosan solution with a mass fraction of 3% was taken, 100 μ L of the aqueous solution of aldehyde-functionalized PEG with a mass fraction of 20% was added, and mixed uniformly on a vortex shaker to prepare the hydrogel dressing (HG).
(2) Rheological analysis of HG
The gelling property and the mechanical property of the hydrogel of the invention were analyzed by a rheometer, as shown in fig. 2(a), the storage modulus gradually increased with the detection time, and the dynamic crosslinking process of the schiff base hydrogel and the rapid-forming property of the hydrogel were verified. The viscoelasticity test results in fig. 2(b) show that the gel has better mechanical strength in a certain frequency range, and the property is favorable for prolonging the service time of the gel as a dressing.
(3) HG has antioxidant, tissue adhesion, self-healing and hemostatic properties
Bacterial infected wounds after photodynamic and photothermal therapy produce a large amount of highly active substances, such as free radicals, reactive oxygen species, etc., due to inflammatory reactions. The presence of these highly active substances causes oxidative stress of the cells, leading to lipid peroxidation, DNA damage and enzyme inactivation, which are detrimental to wound healing and, even more, to wound deterioration. According to the report of the literature, the dressing with oxidation resistance can promote wound healing, and the oxidation resistance of hydrogel HG is investigated by selecting stable free radical DPPH to test the potential of the hydrogel HG in the aspect of improving the prognosis of a wound surface. As shown in fig. 3(a), the DPPH solution was almost completely captured after 24h incubation with the gel, demonstrating that the gel HG has good antioxidant and anti-inflammatory properties.
The good tissue adhesion can make the dressing better fit the wound surface, and play a role in protecting the wound. In the invention, fresh pigskin is selected as a skin tissue model, the tissue adhesion of the hydrogel HG is tested, and as shown in figure 3(b), the adhesion strength of the HG can reach 13.7 +/-1.5 kPa, which is about that of a commercial dressing
2.7 times of the total weight of the powder.
The Schiff base type hydrogel dressing has certain self-healing and performance due to the existence of dynamic covalent bonds, so that the Schiff base type hydrogel dressing has longer service time and stronger adaptability compared with other types of dressings. As shown in fig. 3(c), hydrogel HG has good self-healing and performance, and meets the performance requirements of an ideal dressing.
Fig. 3(d), a certain amount of HG is added to human whole blood and a tumbling experiment is performed, so that the human whole blood mixed with HG can be kept at the bottom of the centrifuge tube, and the fluidity is reduced, which indicates that HG has certain hemostatic performance.
(4) Testing of cytotoxicity and biocompatibility of HG
As can be seen from fig. 4(a) cytotoxicity test, HG has negligible toxic effect on L929 cells at higher usage amounts. In FIG. 4(b), after co-incubation of HG with blood cells, only negligible hemolysis of blood cells occurs, demonstrating good biocompatibility of HG.
Example 2 Synthesis and characterization of multifunctional nanocomposite dressings
(1) Synthesis of multifunctional nano composite dressing
A100 mL flask was charged with 15mL oleylamine, heated to 65 deg.C, and degassed under vacuum for 1 hour. Then, the temperature is increased to 320 ℃ under the argon protection, and 500 microliter of hexamethyldisilazane is added. At the same time, a precursor solution was prepared: 50mg of WCl6Completely dissolved in 300. mu.L of oleic acid, and 5mL of oleylamine were added, whereupon the solution changed color from dark brown to yellow. Next, 240. mu.L of CS was added rapidly2At this point the color of the solution changed to orange. The precursor solution was injected into the heated hot oil amine solution at a rate of 0.15mL/min using a syringe pump. After the reaction solution was cooled to room temperature, 10mL of n-hexane and 10mL of isopropanol were added to the reaction solution to precipitate WS2Nanosheets. The nanosheets obtained by centrifugation were dried in vacuo at 50 ℃.
Weighing 10mg WS2The nanoplatelets, dispersed with 10mL isopropanol, and 5mL isopropanol solution containing 100mg L-cysteine hydrochloride was added. And (3) treating the reaction solution by using 500w of ultrasonic for 1 hour, and collecting the modified nanosheets by using centrifugation. The precipitate was washed three times with a mixed solution of isopropanol and water (v/v ═ 1: 1). Finally, the precipitate was dried under vacuum at 50 ℃.
Synthetic WS2Transmission electron microscopy of nanoplatelets see fig. 5 (a).
50mg ciprofloxacin and 15 mg WS2NSs were dispersed in 50ml of deionized water, incubated together in a rotary mixer for 24 hours, and then unadsorbed ciprofloxacin was removed by centrifugation and deionized water washing.
An acetic acid solution of alkylated chitosan with a mass fraction of 3% (acetic acid concentration 0.2M) and an aqueous solution of aldehyde-functionalized polyethylene glycol with a mass fraction of 20% were prepared, respectively.
2mg ciprofloxacin-loaded WS2The nanoplatelets were mixed with 0.3g of 3% alkylated chitosan solution, 100 μ L of 20% aqueous solution of aldehyde-functionalized polyethylene glycol was added, and mixed well on a vortex shaker to prepare multifunctional nanocomposite dressing (HG-WC). The scanning electron microscope image thereof is shown in FIG. 10.
(2) Photothermal nanomaterial WS2Synthesis of nanosheet and study of photothermal properties
FIG. 5(a) is a transmission electron microscope image of photo-thermal nano-material tungsten disulfide nanosheet, and FIG. 5(b) is an XPS spectrum of tungsten disulfide nanosheet, which proves that the synthesized WS is2The nano sheet is a 2T type nano material. FIG. 5(c) shows the concentration of the nano-material at 0.5w/cm2Photo-thermal properties under illumination intensity, FIG. 5(d) is photo-thermal nanomaterial WS2Proved by the thermal stability test of WS2The nano-sheet has good photo-thermal conversion efficiency and thermal stability, and can be applied to photo-thermal treatment of bacterial infection.
(3) Construction of nanocomposite dressing and study of therapeutic properties thereof
WS obtained by preparation2The nano-sheet is loaded with antibacterial drugs and is mixed with hydrogel HG to prepare the nano-composite dressing HG-WC. Fig. 6(a) investigates the photoresponsive drug release properties of the nanocomposite dressing, demonstrating that the dressing can be controllably administered. Fig. 6(b) investigates the photothermal properties of the nanocomposite dressing, demonstrating that the material has photothermal therapeutic properties. Fig. 6(c) uses a scanning electron microscope to study the synergistic antibacterial effect of the nano composite dressing under near-infrared light irradiation, and it can be seen that the bacterial cell wall after dressing treatment is broken and the complete bacterial morphology is lost, thus proving the good antibacterial performance of the composite dressing.
(4) Application of nano composite dressing in treatment of wounds infected by living bacteria
In order to detect the living body antibacterial effect and the performance of promoting wound healing of the nano-composite dressing HG-WC, the invention applies the composite dressing HG-WC to the mouse bacterial infection wound. The method comprises the following specific steps: a mouse bacterial infection wound model is constructed, HG-WC is used for treating bacterial infection, the dressing is replaced every 1 day, the healing condition of the mouse wound surface is observed within a 5-day observation period (figure 7), and as can be seen from figure 7, the nano composite dressing has good living body antibacterial effect and the performance of promoting wound healing.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (10)
1. The hydrogel dressing is characterized in that the hydrogel dressing is a hydrogel with a net structure, and the hydrogel is obtained by covalently crosslinking aldehyde-functionalized polyethylene glycol and alkylated chitosan;
the alkylated chitosan has the following structural formula:
the aldehyde group functionalized polyethylene glycol has the following structural formula:
2. the hydrogel dressing of claim 1, wherein the aldehyde-functionalized polyethylene glycol is prepared by the following method:
0.5g of 4-aldehyde benzoic acid, 1.6g of PEG 2000 and 0.025g of 4-dimethylaminopyridine were dissolved in 50mL of tetrahydrofuran, 0.84g of dicyclohexylcarbodiimide was added, and the reaction was stirred at room temperature overnight; filtering off the resulting white solid; the filtrate is purified for 3 times by dissolving with tetrahydrofuran and then adding ether for precipitation to prepare the aldehyde group functionalized polyethylene glycol.
3. The hydrogel dressing of claim 1, wherein the alkylated chitosan is prepared by a method comprising:
1g of chitosan is firstly dissolved in 50mL of 0.2M acetic acid solution, and then 40mL of ethanol is added; adjusting the pH value of the solution to 5.1, then adding 0.01eq of dodecanal with the mole number of chitosan amino groups, reacting for 20min, and introducing excessive sodium cyanoborohydride to reduce generated imine bonds; after continuing to react for 18h, adding 50mL of ethanol to precipitate the generated alkylated chitosan, and centrifuging to obtain a precipitate; washing the precipitate with ethanol for 3 times to obtain final product alkylated chitosan.
4. A method of making the hydrogel dressing of claim 1, comprising the steps of:
mixing the alkylated chitosan acetic acid aqueous solution with the aldehyde group functionalized polyethylene glycol aqueous solution, and carrying out rapid crosslinking reaction under the condition of shaking at room temperature to prepare the hydrogel dressing.
5. The method for preparing a hydrogel dressing according to claim 4, wherein the mass fraction of the aqueous solution of alkylated chitosan acetic acid is 3% and the mass fraction of the aqueous solution of aldehyde-functionalized polyethylene glycol is 20%.
6. A multifunctional nanocomposite dressing, which is obtained by loading a photothermal nanomaterial and an antibacterial drug into the network structure of the hydrogel dressing of claim 1.
7. The multifunctional nanocomposite dressing of claim 6, wherein the antimicrobial drug is supported on the photothermal nanomaterial.
8. The multifunctional nanocomposite dressing of claim 6, wherein the photothermal nanomaterial is WS2Nanosheets, the antibacterial agent being ciprofloxacin.
9. The method of making the multifunctional nanocomposite dressing of claim 6, comprising the steps of:
step 1, synthesizing a photo-thermal nano material;
step 2, loading antibacterial drugs
Dispersing the antibacterial drug and the photo-thermal nano material in deionized water, co-incubating in a rotary mixer, and then removing the unadsorbed antibacterial drug by centrifugation and deionized water washing to obtain the photo-thermal nano material loaded with the antibacterial drug;
step 3, synthesis of multifunctional nano composite dressing
Preparing an acetic acid solution of alkylated chitosan and an aqueous solution of aldehyde-functionalized polyethylene glycol, respectively;
the photo-thermal nano material loaded with the antibacterial drug is mixed with acetic acid solution of alkylated chitosan, aqueous solution of aldehyde group functionalized polyethylene glycol is added, and the mixture is uniformly mixed on a vortex oscillator to prepare the multifunctional nano composite dressing.
10. Use of the multifunctional nanocomposite dressing of claim 6 for the healing of a bacterially infected wound.
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