A kind of nanofiber functional dressing for burn and scald wound healing

Abstract

The application discloses a kind of nanofiber functional dressings for burn and scald wound healing, belong to the technical field of wound repair dressings.The dressing is prepared by double-layer electrospinning, comprising hydrophilic nanofiber layer and hydrophobic nanofiber layer.The hydrophobic nanofiber layer is prepared by electrospinning of antibacterial composite modified material and isocyanate-terminated oligomeric lactic acid, and the antibacterial composite modified material is prepared by reacting (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid after acyl chloride with N,N-bis(2-benzimidazole methyl)amine, and then by quaternary ammonium chloride reaction.The rigid structure of tetraoxaspiro ring improves thermal stability and inhibits molecular chain water swelling;Quaternary ammonium benzimidazole group can efficiently resist bacteria by destroying cell membrane through positive charge.The urea bond formed by amide bond in hydrophilic layer and isocyanate group of antibacterial material significantly improves the liquid absorption capacity;The hydrophobic layer provides mechanical support and ductility;Heat treatment makes the interface of two layers fuse, and the overall tear strength is improved, which meets the demand of joint activity.

Description

Technical Field

[0001] This invention belongs to the field of wound repair dressing technology, and particularly relates to a nanofiber functional dressing for the healing of burn wounds. Background Technology

[0002] Burns and scalds are common skin and tissue injuries, and their wounds have the following significant characteristics: severely impaired or even lost skin barrier function, leading to massive exudation of tissue fluid; the wound environment is highly susceptible to the growth of pathogenic microorganisms such as bacteria and fungi, causing infection; and the activity of endogenous enzymes and growth factors in the damaged tissue is inhibited, resulting in a slow healing process. Therefore, an ideal burn dressing must possess multiple functions: highly efficient absorption of exudate to maintain a moderately moist microenvironment, providing strong and long-lasting antibacterial protection, good biocompatibility, suitable mechanical strength, and a stable physicochemical structure.

[0003] Currently, there are many types of dressings used in clinical practice, but they still have many limitations. Traditional dressings (such as gauze) have limited absorbency, are prone to adhering to the wound surface and causing secondary damage, and have insufficient antibacterial properties. Although hydrogel dressings can provide a moist environment, their mechanical strength is usually poor, they are easily damaged, and they are not good at managing wounds with large amounts of exudate. For example, Chinese invention patent application number 201210444974.X discloses an antibacterial dressing for deeply infected wounds, whose core antibacterial component is nano-silver. Although nano-silver has a broad antibacterial spectrum, there are risks that nano-silver particles are prone to aggregation, leading to a decrease in antibacterial efficacy, and that long-term use may result in absorption and deposition by the human body, producing potential biotoxicity. In addition, many existing dressings cannot simultaneously achieve excellent absorbency, strong antibacterial activity, good mechanical support, and flexibility. Therefore, developing a new type of functional dressing is of great significance for promoting rapid and safe healing of burn wounds, reducing the risk of infection, and improving patient prognosis. Summary of the Invention

[0004] In view of the above situation and to overcome the shortcomings of the prior art, the present invention provides a nanofiber functional dressing that combines high-efficiency liquid absorption capacity, long-lasting and strong antibacterial properties, excellent mechanical strength and good biocompatibility. This effectively solves the limitations of existing burn dressings in terms of liquid absorption capacity, antibacterial effect, mechanical support and safety, thereby accelerating the healing process of burn wounds, reducing the risk of infection and improving the quality of healing.

[0005] To achieve the above objectives, the following technical solution is adopted: This invention provides a nanofiber functional dressing for burn wound healing, prepared through the following steps:

[0006] S1. The antibacterial composite modified material and isocyanate-terminated oligolactic acid are mixed at a mass ratio of 1:1-3 and dissolved in a mixed solvent of chloroform and N,N-dimethylacetamide at a volume ratio of 3-5:1 to form a first spinning solution with a total solid content of 10-20wt%. The first spinning solution is electrospun to obtain a hydrophilic nanofiber layer.

[0007] S2. Polycaprolactone is dissolved in a mixed solvent of dichloromethane and N,N-dimethylformamide in a volume ratio of 3-5:1 to form a second spinning solution with a mass concentration of 8-15wt%. The second spinning solution is electrospun on the surface of the hydrophilic nanofiber layer to form a hydrophobic nanofiber layer covering the hydrophilic nanofiber layer, forming a bilayer structure. Then, it is heat-treated at 50-70℃ for 8-24h to obtain the nanofiber functional dressing.

[0008] Furthermore, the antibacterial composite modified material is prepared through the following steps:

[0009] (1) Under nitrogen protection, (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid was dissolved in anhydrous dichloromethane, then cooled to 0-5℃, and a mixed solution of thionyl chloride and N,N-dimethylformamide was slowly added dropwise. After the addition was completed, the temperature was raised to 20-30℃ and reacted for 3-6 h. The solvent and excess thionyl chloride were removed by vacuum distillation to obtain intermediate A.

[0010] (2) Dissolve intermediate A in dichloromethane, cool to 0-5℃, add dropwise anhydrous tetrahydrofuran solution containing N,N-bis(2-benzimidazole methyl)amine and triethylamine, after the addition is complete, heat to 50-70℃ and reflux for 10-15h, then cool to room temperature, add water to precipitate solid, filter, and wash with cold water to obtain intermediate B;

[0011] (3) Add intermediate B and potassium carbonate to N,N-dimethylformamide, stir at 50-80℃ for 0.5-2h, slowly add benzyl chloride, continue the reaction for 20-30h, cool to room temperature, filter to remove solid, pour the filtrate into 3-5 times the volume of ethanol to precipitate, collect the precipitate and wash it 3 times with ethanol, dissolve the product in deionized water, dialyze with a dialysis bag with a molecular weight cutoff of 3000-5000 Da for 40-50h, and freeze dry to obtain antibacterial composite modified material.

[0012] Further, in step (1), the feeding ratio of (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid, dichloromethane, thionyl chloride, and N,N-dimethylformamide is 8-12g: 120-150mL: 50-80mL: 0.3-0.5mL.

[0013] Further, in step (2), the feeding ratio of intermediate A, dichloromethane, N,N-bis(2-benzimidazole methyl)amine, triethylamine, and anhydrous tetrahydrofuran is 8-15g: 200-220mL: 5.2-7.5g: 10-15mL: 10-20mL.

[0014] Furthermore, in step (3), the feeding ratio of intermediate B, potassium carbonate, N,N-dimethylformamide, and benzyl chloride is 7-10g: 120-150mL: 4.2-6g.

[0015] Furthermore, in step S1, the isocyanate-terminated oligolactic acid is hexamethylene diisocyanate-terminated oligolactic acid with a number average molecular weight of 2000-5000 Da and an isocyanate group content of 1.0-3.0 wt%.

[0016] Furthermore, in step S2, the number average molecular weight of polycaprolactone is 50,000-100,000 Da, the thickness of the hydrophobic nanofiber layer is 100-300 μm, and the thickness of the hydrophilic nanofiber layer is 50-150 μm.

[0017] Furthermore, in step S1, the spinning voltage is 12-18kV, the receiving distance is 10-20cm, the flow rate is 0.3-1.0mL / h, and the ambient humidity is ≤40%.

[0018] Furthermore, in step S2, the spinning voltage is 15-20kV, the receiving distance is 15-25cm, the flow rate is 0.8-1.5mL / h, and the ambient humidity is ≤40%.

[0019] The beneficial effects of this invention are:

[0020] The central secondary amine nitrogen in the antibacterial composite modified material reacts with acyl chloride (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid. The rigid structure of the tetraoxaspiro ring significantly improves the thermal stability and spatial orientation of the molecular chain, restricts the flexible movement of the molecular chain, reduces the disordered entanglement of polymer chains during electrospinning, ensures the uniformity of the material structure, and inhibits the excessive expansion of the molecular chain after water absorption through the rigid skeleton.

[0021] The benzimidazole group itself has antibacterial activity. After the benzyl chloride quaternization reaction, it forms a quaternary ammonium salt structure with a strong positive charge, which can disrupt the cell membrane integrity. It shows highly effective antibacterial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans, and effectively prevents wound infection.

[0022] In the antibacterial composite modified material, the secondary amine group of the benzimidazole ring reacts with the isocyanate group of the isocyanate-terminated oligolactic acid to form a stable urea group. This is then electrospun into a hydrophilic nanofiber layer. At the same time, the abundant hydrophilic amide bonds in the molecular chain significantly improve the water absorption rate of the dressing, efficiently absorb wound tissue fluid, and maintain a moist healing environment.

[0023] The hydrophobic nanofiber layer provides high ductility and mechanical support, blocking external pathogens, while the hydrophilic nanofiber layer ensures biocompatibility, rapidly absorbs liquid and reduces wound exudation. The two layers are fused together through heat treatment, which improves the overall tear resistance of the dressing and makes it suitable for use in active areas such as joints. Attached Figure Description

[0024] Figure 1 The bar chart shows the tensile strength test results of the nanofiber functional dressings of Examples 1-3 and Comparative Example 1 of this invention.

[0025] Figure 2 The bar chart shows the cytotoxicity test results of the nanofiber functional dressings of Examples 1-3 and Comparative Example 1 of this invention.

[0026] Figure 3 The bar chart shows the antibacterial test results of the nanofiber functional dressings of Examples 1-3 and Comparative Example 1 of this invention.

[0027] Figure 4 This is a wound state diagram of the nanofiber functional dressing of Example 3 of the present invention in a rat burn wound healing experiment.

[0028] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation

[0029] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0031] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the experimental materials used in the following examples are all purchased from commercial channels.

[0032] Example 1: A nanofiber functional dressing for burn wound healing, prepared through the following steps:

[0033] S1. The antibacterial composite modified material and isocyanate-terminated oligolactic acid are mixed at a mass ratio of 1:1 and dissolved in a mixed solvent of chloroform and N,N-dimethylacetamide at a volume ratio of 3:1 to form a first spinning solution with a total solid content of 10wt%. The first spinning solution is electrospun to obtain a hydrophilic nanofiber layer.

[0034] S2. Polycaprolactone is dissolved in a mixed solvent of dichloromethane and N,N-dimethylformamide in a volume ratio of 3:1 to form a second spinning solution with a mass concentration of 8wt%. The second spinning solution is electrospun on the surface of the hydrophilic nanofiber layer to form a hydrophobic nanofiber layer covering the hydrophilic nanofiber layer, forming a bilayer structure. Then, it is heat-treated at 50°C for 8 hours to obtain a nanofiber functional dressing.

[0035] The antibacterial composite modified material is prepared through the following steps:

[0036] (1) Under nitrogen protection, 8g of (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid was dissolved in 120mL of anhydrous dichloromethane, cooled to 0℃, and 50mL of a mixed solution of thionyl chloride and 0.3mL of N,N-dimethylformamide was slowly added dropwise. After the addition was completed, the temperature was raised to 20℃ and reacted for 3h. The solvent and excess thionyl chloride were removed by vacuum distillation to obtain intermediate A.

[0037] (2) Dissolve 8g of intermediate A in 200mL of dichloromethane, cool to 0℃, add dropwise a solution containing 5.2g of N,N-bis(2-benzimidazole methyl)amine, 10mL of triethylamine and 10mL of anhydrous tetrahydrofuran, and after the addition is complete, heat to 50℃ and reflux for 10h, cool to room temperature, add water to precipitate the solid, filter, wash with cold water to obtain intermediate B;

[0038] (3) Add 7g of intermediate B and 4.2g of potassium carbonate to 120mL of N,N-dimethylformamide, stir at 50℃ for 0.5h, slowly add 4.2g of benzyl chloride, continue the reaction for 20h, cool to room temperature, filter to remove solid, pour the filtrate into 3 times the volume of ethanol to precipitate, collect the precipitate and wash it 3 times with ethanol, dissolve the product in deionized water, dialyze it for 40h using a dialysis bag with a molecular weight cutoff of 3000Da, and freeze dry to obtain antibacterial composite modified material.

[0039] In step S1, the isocyanate-terminated oligolactic acid is hexamethylene diisocyanate-terminated oligolactic acid with a number average molecular weight of 2000 Da and an isocyanate group content of 1.0 wt%.

[0040] In step S2, the number-average molecular weight of polycaprolactone is 50,000 Da, the thickness of the hydrophobic nanofiber layer is 100 μm, and the thickness of the hydrophilic nanofiber layer is 50 μm.

[0041] In step S1, the spinning voltage is 12kV, the receiving distance is 10cm, the flow rate is 0.3mL / h, and the ambient humidity is ≤40%.

[0042] In step S2, the spinning voltage is 15kV, the receiving distance is 15cm, the flow rate is 0.8mL / h, and the ambient humidity is ≤40%.

[0043] Example 2: A nanofiber functional dressing for burn wound healing, prepared through the following steps:

[0044] S1. The antibacterial composite modified material and isocyanate-terminated oligolactic acid are mixed at a mass ratio of 1:3 and dissolved in a mixed solvent of chloroform and N,N-dimethylacetamide at a volume ratio of 5:1 to form a first spinning solution with a total solid content of 20wt%. The first spinning solution is electrospun to obtain a hydrophilic nanofiber layer.

[0045] S2. Polycaprolactone is dissolved in a mixed solvent of dichloromethane and N,N-dimethylformamide in a volume ratio of 5:1 to form a second spinning solution with a mass concentration of 15wt%. The second spinning solution is electrospun on the surface of the hydrophilic nanofiber layer to form a hydrophobic nanofiber layer covering the hydrophilic nanofiber layer, forming a bilayer structure. Then, it is heat-treated at 70°C for 24 hours to obtain a nanofiber functional dressing.

[0046] The antibacterial composite modified material is prepared through the following steps:

[0047] (1) Under nitrogen protection, 12 g of (9Cl)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid was dissolved in 150 mL of anhydrous dichloromethane, cooled to 5 °C, and 80 mL of a mixed solution of thionyl chloride and 0.5 mL of N,N-dimethylformamide was slowly added dropwise. After the addition was completed, the temperature was raised to 30 °C and reacted for 6 h. The solvent and excess thionyl chloride were removed by vacuum distillation to obtain intermediate A.

[0048] (2) Dissolve 15g of intermediate A in 220mL of dichloromethane, cool to 5℃, add dropwise a solution containing 7.5g of N,N-bis(2-benzimidazole methyl)amine, 15mL of triethylamine and 20mL of anhydrous tetrahydrofuran, and after the addition is complete, heat to 70℃ and reflux for 15h, cool to room temperature, add water to precipitate the solid, filter, wash with cold water to obtain intermediate B;

[0049] (3) Add 10g of intermediate B and 6g of potassium carbonate to 150mL of N,N-dimethylformamide, stir at 80℃ for 2h, slowly add 6g of benzyl chloride, continue the reaction for 30h, cool to room temperature, filter to remove solid, pour the filtrate into 5 times the volume of ethanol to precipitate, collect the precipitate and wash it 3 times with ethanol, dissolve the product in deionized water, dialyze it for 50h using a dialysis bag with a molecular weight cutoff of 5000Da, and freeze dry to obtain antibacterial composite modified material.

[0050] In step S1, the isocyanate-terminated oligolactic acid is hexamethylene diisocyanate-terminated oligolactic acid with a number average molecular weight of 5000 Da and an isocyanate group content of 3.0 wt%.

[0051] In step S2, the number-average molecular weight of polycaprolactone is 100,000 Da, the thickness of the hydrophobic nanofiber layer is 300 μm, and the thickness of the hydrophilic nanofiber layer is 150 μm.

[0052] In step S1, the spinning voltage is 18kV, the receiving distance is 20cm, the flow rate is 1.0mL / h, and the ambient humidity is ≤40%.

[0053] In step S2, the spinning voltage is 20kV, the receiving distance is 25cm, the flow rate is 1.5mL / h, and the ambient humidity is ≤40%.

[0054] Example 3: A nanofiber functional dressing for burn wound healing, prepared through the following steps:

[0055] S1. The antibacterial composite modified material and isocyanate-terminated oligolactic acid are mixed at a mass ratio of 1:2 and dissolved in a mixed solvent of chloroform and N,N-dimethylacetamide at a volume ratio of 4:1 to form a first spinning solution with a total solid content of 15wt%. The first spinning solution is electrospun to obtain a hydrophilic nanofiber layer.

[0056] S2. Polycaprolactone is dissolved in a mixed solvent of dichloromethane and N,N-dimethylformamide in a volume ratio of 4:1 to form a second spinning solution with a mass concentration of 12wt%. The second spinning solution is electrospun on the surface of the hydrophilic nanofiber layer to form a hydrophobic nanofiber layer covering the hydrophilic nanofiber layer, forming a bilayer structure. Then, it is heat-treated at 60°C for 16 hours to obtain a nanofiber functional dressing.

[0057] The antibacterial composite modified material is prepared through the following steps:

[0058] (1) Under nitrogen protection, 10 g of (9Cl)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid was dissolved in 135 mL of anhydrous dichloromethane, cooled to 3 °C, and a mixed solution of 65 mL of thionyl chloride and 0.4 mL of N,N-dimethylformamide was slowly added dropwise. After the addition was completed, the temperature was raised to 25 °C and reacted for 4.5 h. The solvent and excess thionyl chloride were removed by vacuum distillation to obtain intermediate A.

[0059] (2) Dissolve 11.5g of intermediate A in 210mL of dichloromethane, cool to 3℃, add dropwise a solution containing 6.35g of N,N-bis(2-benzimidazole methyl)amine, 12.5mL of triethylamine and 15mL of anhydrous tetrahydrofuran, and after the addition is complete, heat to 60℃ and reflux for 12.5h, cool to room temperature, add water to precipitate the solid, filter, wash with cold water to obtain intermediate B;

[0060] (3) Add 8.5g of intermediate B and 5.1g of potassium carbonate to 135mL of N,N-dimethylformamide, stir at 65℃ for 1.25h, slowly add 5.1g of benzyl chloride, continue the reaction for 25h, cool to room temperature, filter to remove solid, pour the filtrate into 4 times the volume of ethanol to precipitate, collect the precipitate and wash it 3 times with ethanol, dissolve the product in deionized water, dialyze it for 45h using a dialysis bag with a molecular weight cutoff of 4000Da, and freeze dry to obtain antibacterial composite modified material.

[0061] In step S1, the isocyanate-terminated oligolactic acid is hexamethylene diisocyanate-terminated oligolactic acid with a number average molecular weight of 3500 Da and an isocyanate group content of 2.0 wt%.

[0062] In step S2, the number-average molecular weight of polycaprolactone is 75,000 Da, the thickness of the hydrophobic nanofiber layer is 200 μm, and the thickness of the hydrophilic nanofiber layer is 100 μm.

[0063] In step S1, the spinning voltage is 15kV, the receiving distance is 15cm, the flow rate is 0.65mL / h, and the ambient humidity is ≤40%.

[0064] In step S2, the spinning voltage is 18kV, the receiving distance is 20cm, the flow rate is 1.15mL / h, and the ambient humidity is ≤40%.

[0065] Comparative Example 1: The hydrophilic nanofiber layer in this comparative example was replaced with a polyethylene glycol-polylactic acid copolymer, with a mass ratio of polyethylene glycol to polylactic acid of 70:30. The copolymer was dissolved in a mixed solvent of chloroform and N,N-dimethylacetamide in a volume ratio of 4:1 to form a first spinning solution with a total solid content of 15 wt%. The first spinning solution was electrospun to obtain the hydrophilic nanofiber layer. All other aspects were the same as in Example 3.

[0066] Test Example 1: Tensile Strength Test of Functional Dressings

[0067] The dressing samples prepared in Examples 1-3 and Comparative Example 1 were cut into rectangular strips of 50mm × 10mm. Tensile strength tests were performed using a WDW-3020 electronic universal testing machine with a clamp spacing of 30mm and a tensile speed of 100mm / min. Each group was tested 5 times. The test results are shown below. Figure 1 .

[0068] Depend on Figure 1 It can be seen that the functional dressing prepared by the present invention exhibits high tensile strength. Compared with Comparative Example 1, the modified tear resistance is improved. Therefore, the functional dressing can meet the usage requirements of active parts such as joints.

[0069] Test Example 2: Functional Dressing Cytotoxicity Test

[0070] (1) Preparation of material extract: After cutting the dressing samples prepared in Examples 1-3 and Comparative Example 1 into small pieces, DMEM medium was added at a ratio of 0.1 g / mL. The samples were extracted in a 37℃, 5% CO2 incubator for 24 h. The extract was then filtered through a 0.22 μm filter membrane to remove bacteria, thus obtaining the material extract.

[0071] (2) Cell seeding: Mouse epithelial cells in the logarithmic growth phase were digested with 0.25% trypsin and the cell concentration was adjusted to 5 × 10⁻⁶ cells / year. 4 The fractions were inoculated at a rate of 100 μL / mL into 96-well plates and incubated at 37°C in a 5% CO2 incubator for 24 h.

[0072] (3) Drug treatment: Discard the original culture medium in the wells and add material extracts of different concentrations (100%, 50%, 25%) of Examples 1-3 and Comparative Example 1 respectively, 100 μL per well, 5 replicates per group, and continue to culture for 24h and 48h.

[0073] (4) Detection: Add 10 μL CCK-8 solution to each well, continue culturing for 4 h, and then use an ELISA reader to measure the absorbance (OD value) of each well at a wavelength of 450 nm.

[0074] (5) Calculate cell viability: Cell viability (%) = (OD value of experimental group - OD value of blank group) / (OD value of negative control group - OD value of blank group) × 100%.

[0075] The above test results are shown in Figure 2 .

[0076] Depend on Figure 2 It can be seen that the functional dressing prepared by the present invention exhibits low toxicity at different concentrations, comparable to the cytotoxicity of Comparative Example 1, indicating that the hydrophilic fiber layer prepared by the preparation method of the present invention exhibits similar biocompatibility to the hydrophilic nanofiber layer prepared by polyethylene glycol-polylactic acid copolymer.

[0077] Test Example 3: Antibacterial Test of Functional Dressings

[0078] (1) Preparation of bacterial culture: Staphylococcus aureus and Escherichia coli were inoculated on nutrient agar medium and cultured at 37°C for 24 h; Candida albicans was inoculated on Sabouraud dextrose agar medium and cultured at 28°C for 48 h. Single colonies were picked and inoculated into the corresponding liquid culture medium and cultured on a shaker at 37°C (28°C for Candida albicans) until the logarithmic growth phase. The bacterial culture concentration was adjusted to 10 with physiological saline. 6 CFU / mL.

[0079] (2) Determination of antibacterial rate: Mix 100 μL of bacterial suspension with 100 μL of dressing extract (preparation method as in Test Example 2), incubate at 37℃ (28℃ for Candida albicans) for 2 h, then spread 100 μL of the mixture onto the corresponding agar plate, and count the number of colonies after incubation. Antibacterial rate (%) = (number of colonies in control group - number of colonies in experimental group) / number of colonies in control group × 100%.

[0080] The above test results are shown in Figure 3 .

[0081] from Figure 3 It can be seen that the functional dressing prepared by this invention exhibits highly effective antibacterial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans, thus effectively preventing wound infection.

[0082] Test Example 4: Functional Dressings in the Healing of Burn Wounds in Rats

[0083] (1) Establishment of SD rat burn model: After 6 weeks of acclimatization feeding, SD rats (6 weeks old, weighing 160-200g) were anesthetized by intraperitoneal injection of 10% chloral hydrate (3mL / kg), their backs were shaved, and a copper rod with a diameter of 15mm was heated in an 80℃ constant temperature water bath for 5 minutes. Then, it was pressed vertically on the shaved area of ​​the rat's back for 3 seconds to create a deep second-degree burn wound.

[0084] (2) Functional dressing repair: 30 rats were randomly divided into 3 groups of 10 each: blank group (wound covered with saline gauze), control group (dressing covered with Comparative Example 1), and experimental group (dressing covered with Example 3). After the operation, the skin around the wound was disinfected with povidone-iodine every day, the dressing was changed, and the wound healing was observed.

[0085] (3) Observation of healing status: The healing status of the rat wound was observed on the 7th and 14th day after surgery. The results are shown in the figure. Figure 4 .

[0086] Depend on Figure 4 It can be seen that, compared with the blank group, the burn wounds of rats in the control group and the experimental group healed significantly faster, and the healing speed of the experimental group was better than that of the control group. The wounds were basically healed by the 14th day after the operation, and the repair effect was the best. This shows that the nanofiber functional dressing has a good ability to promote repair, can promote the healing of burn wounds, and reduce symptoms such as infection and inflammation.

[0087] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0088] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A nanofiber functional dressing for healing burn wounds, characterized in that: Prepared by the following steps: S1. The antibacterial composite modified material and isocyanate-terminated oligolactic acid are mixed at a mass ratio of 1:1-3 and dissolved in a mixed solvent of chloroform and N,N-dimethylacetamide at a volume ratio of 3-5:1 to form a first spinning solution with a total solid content of 10-20wt%. The first spinning solution is electrospun to obtain a hydrophilic nanofiber layer. S2. Polycaprolactone is dissolved in a mixed solvent of dichloromethane and N,N-dimethylformamide in a volume ratio of 3-5:1 to form a second spinning solution with a mass concentration of 8-15wt%. The second spinning solution is electrospun on the surface of the hydrophilic nanofiber layer to form a hydrophobic nanofiber layer covering the hydrophilic nanofiber layer, forming a bilayer structure. Then, it is heat-treated at 50-70℃ for 8-24h to obtain a nanofiber functional dressing. The antibacterial composite modified material is prepared through the following steps: (1) Under nitrogen protection, (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid was dissolved in anhydrous dichloromethane, then cooled to 0-5℃, and a mixed solution of thionyl chloride and N,N-dimethylformamide was slowly added dropwise. After the addition was completed, the temperature was raised to 20-30℃ and reacted for 3-6 h. The solvent and excess thionyl chloride were removed by vacuum distillation to obtain intermediate A. (2) Dissolve intermediate A in dichloromethane, cool to 0-5℃, add dropwise anhydrous tetrahydrofuran solution containing N,N-bis(2-benzimidazole methyl)amine and triethylamine, after the addition is complete, heat to 50-70℃ and reflux for 10-15h, then cool to room temperature, add water to precipitate solid, filter, and wash with cold water to obtain intermediate B; (3) Add intermediate B and potassium carbonate to N,N-dimethylformamide, stir at 50-80℃ for 0.5-2h, slowly add benzyl chloride, continue the reaction for 20-30h, cool to room temperature, filter to remove solid, pour the filtrate into 3-5 times the volume of ethanol to precipitate, collect the precipitate and wash it 3 times with ethanol, dissolve the product in deionized water, dialyze with a dialysis bag with a molecular weight cutoff of 3000-5000 Da for 40-50h, and freeze dry to obtain antibacterial composite modified material.

2. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step (1), the feeding ratio of (9CI)-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-dipropionic acid, dichloromethane, thionyl chloride, and N,N-dimethylformamide is 8-12g: 120-150mL: 50-80mL: 0.3-0.5mL.

3. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step (2), the feeding ratio of intermediate A, dichloromethane, N,N-bis(2-benzimidazole methyl)amine, triethylamine, and anhydrous tetrahydrofuran is 8-15g: 200-220mL: 5.2-7.5g: 10-15mL: 10-20mL.

4. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step (3), the feeding ratio of intermediate B, potassium carbonate, N,N-dimethylformamide, and benzyl chloride is 7-10g: 120-150mL: 4.2-6g.

5. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step S1, the isocyanate-terminated oligolactic acid is hexamethylene diisocyanate-terminated oligolactic acid with a number average molecular weight of 2000-5000 Da and an isocyanate group content of 1.0-3.0 wt%.

6. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step S2, the number-average molecular weight of polycaprolactone is 50,000-100,000 Da, the thickness of the hydrophobic nanofiber layer is 100-300 μm, and the thickness of the hydrophilic nanofiber layer is 50-150 μm.

7. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step S1, the spinning voltage is 12-18kV, the receiving distance is 10-20cm, the flow rate is 0.3-1.0mL / h, and the ambient humidity is ≤40%.

8. The nanofiber functional dressing for burn wound healing according to claim 1, characterized in that: In step S2, the spinning voltage is 15-20kV, the receiving distance is 15-25cm, the flow rate is 0.8-1.5mL / h, and the ambient humidity is ≤40%.

Images