An anti-infective and healing-promoting alginate dressing

Abstract

This invention provides an anti-infective and healing-promoting alginate dressing, belonging to the field of medical dressing technology. The dressing comprises an antibacterial barrier layer, an alginate multifunctional layer, and a one-way moisture-wicking layer arranged sequentially. The antibacterial barrier layer is a PCL / alginate (SA) membrane. The alginate multifunctional layer contains bioactive glass, nano-ZnO, and alginate dressing components. The one-way moisture-wicking layer is a PCL membrane. All layers are composited using a hot-pressing process. This invention constructs a high-performance alginate multifunctional dressing formulation and designs the composite process for each layer, while controlling the porosity of the antibacterial barrier membrane. This invention combines alginate dressing with bioactive glass to achieve dual functions of promoting healing and anti-infection, resulting in outstanding efficacy. Furthermore, the main body of the dressing contains no drug components, making it safe and reliable to use.

Description

Technical Field

[0001] This invention relates to the field of medical dressing technology, specifically to an anti-infective and healing-promoting alginate dressing. Background Technology

[0002] Alginate is a natural polysaccharide carbohydrate extracted from seaweed. It possesses excellent biocompatibility and biodegradability, making alginate dressings promising for applications in the field of biomedical materials. As a functional wound dressing, alginate dressings offer multiple benefits, including absorbing exudate, promoting wound healing, and preventing infection. These functions rely on its unique chemical structure and physical properties, such as high hygroscopicity, hemostatic properties, and gelling properties.

[0003] The broad application prospects of alginate dressings in wound care are remarkable. They are not only suitable for general skin trauma, burns, and ulcers, but can also be extended to the treatment of refractory wounds such as diabetic foot, venous ulcers, and pressure ulcers. Furthermore, with the continuous development of biomedical technology, polysaccharide dressings may be combined with other treatment methods (such as gene therapy and stem cell therapy) to provide a more comprehensive and effective solution for wound care.

[0004] In current medical practice, there is a widespread need for dressings that can effectively promote wound healing and prevent infection, as wound dressings play a crucial role in the healing process. Currently, zinc alginate, calcium alginate, and sodium alginate complexes are commonly used clinically. While calcium alginate dressings can achieve hemostasis, they lack additional benefits such as antibacterial properties or accelerated wound healing. Therefore, it is essential to develop wound dressings that are adaptable to wounds, non-toxic, biocompatible, antibacterial, moisturizing, have appropriate adhesion (doing not adhere to tissue upon removal), promote skin regeneration to accelerate wound healing, and are cost-effective. Summary of the Invention

[0005] The technical problem to be solved by this invention is: how to develop a wound dressing with better performance.

[0006] To achieve the above technical objectives, the present invention adopts the following technical solution:

[0007] An anti-infective and healing-promoting alginate dressing includes an antibacterial barrier layer, an alginate multifunctional layer, and a one-way moisture-wicking layer;

[0008] The antimicrobial barrier layer is prepared by the following method:

[0009] 1) Dissolve SA in deionized water to prepare an SA aqueous solution of a certain concentration, and let it stand to remove bubbles for later use; homogenize chloroform, SA aqueous solution and Span80 at 7000 r / min for 15 min in a homogenizer, then add PCL and place in a constant temperature shaker for continuous homogenization for 12 h until PCL is completely dissolved. Then homogenize again at 7000 r / min for 15 min to obtain the spinning emulsion; wherein, the mass ratio of PCL to the volume of SA aqueous solution is 1 g: 1 ml, and the mass fraction of Span80 relative to PCL is 66%;

[0010] 2) The emulsion was electrospun to prepare SA / PCL composite fiber membrane; wherein the spinning solution flow rate was 0.65 ml / h, the spinning voltage was 10.5 kV, the receiving distance was 10 cm, the spinning environment temperature was 25±5℃, and the relative humidity was 60±5%.

[0011] The unidirectional moisture-wicking layer is prepared by the following method:

[0012] A) PCL was dissolved in medical acetone at a mass ratio of 1:4, and the solution was obtained by stirring with a magnetic stirrer at room temperature for 4 hours.

[0013] B) Electrospinning was performed on the sample. During the electrospinning process, the solution was poured into 5ml syringes and then installed on the electrospinning equipment for spinning. A needle with an inner diameter of 0.41mm was used, the spinning voltage was 15 kV, the flow rate was 1mL / h, the distance between the needle and the collector was 15cm, and a rotating drum at 300rpm was used as the collector. The obtained sample was dried in a drying oven and then stored in a refrigerator at 4℃.

[0014] Preferably, the alginate multifunctional layer is a bioactive glass / nano-ZnO / alginate dressing, which is prepared by the following method:

[0015] A) 12.2 mL of LTEOS and 7.8 g of Ca(NO3)2·4H2O were added to a solution of 120 mL of deionized water and 40 mL of anhydrous ethanol. The pH of the solution was adjusted to 1.8~2.2 with hydrochloric acid while stirring. Then, 1.3 g of (NH4)2HPO4 was dissolved in deionized water. After it was completely dissolved, polyethylene glycol (PEG-10000) was added and stirred thoroughly. The solution was then poured into the above solution and ammonia was added to adjust the pH to 10. The mixture was stirred for 48 h and then aged in air for 24 h to obtain a white precipitate. The precipitate was freeze-dried in a freeze dryer and then heat-treated in a box furnace at a sintering temperature of 650 °C to obtain nanoscale bioactive glass.

[0016] (b) Spherical ZnO nanoparticles were synthesized by mixing 0.1M zinc acetate dihydrate and 0.025-0.2M sodium hydroxide in methanol. During the synthesis, polyethylene glycol was used as a surfactant, and the reaction mixture was stirred at room temperature for 20 min. The amount of PEG added was 0.08-0.12 g of PEG per gram of ZnO. The precipitate was washed several times with ethanol and deionized water, and then redispersed in deionized water by ultrasound.

[0017] (C) According to the weight proportions, 2-5 parts by weight of sodium alginate, 0.5-1 parts by weight of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and 0.5-1 parts by weight of N-hydroxysuccinimide are added sequentially to 100-200 parts by weight of phosphate buffer solution with pH 6-7 in a certain molar ratio. After stirring evenly, 50-100 parts by weight of methanol solution containing dodecylamine are added. The mixture is stirred at room temperature for 12-24 hours, then precipitated with methanol, centrifuged, dissolved in distilled water, dialyzed for 48-96 hours, and freeze-dried to obtain hydrophobically modified sodium alginate.

[0018] (D) Sodium alginate is completely dissolved in distilled water to form a 10%~15% alginate solution as a spinning solution. The spinning solution is poured into a syringe, and the other end is connected to a nitrogen cylinder. Under nitrogen pressure, a 5%~10% calcium chloride solution is squeezed into the coagulation bath. The gel-like fibers extracted from the coagulation bath are stretched, washed, wound, and dried to obtain calcium alginate fibers.

[0019] (e) Bioactive glass is added to a mixture of water and ethanol, and the powder is uniformly dispersed to form a suspension. The volume ratio of water to ethanol in the mixture is 1:1. 0.5% ZnO nanoparticles are mixed with the suspension and uniformly dispersed. Hydrophobically modified calcium alginate fibers are immersed in saturated KMnO4 for 5-10 minutes, and then washed with distilled water to obtain coarse alginate fibers. The coarse alginate fibers are immersed in the suspension and fully soaked. The suspension is then uniformly sprayed onto the fiber surface, followed by centrifugation to dehydrate. The resulting wet fibers are soaked in an ethanol solution, centrifuged to remove the ethanol, and air-dried naturally. Subsequently, they are vacuum-dried at 60-80℃. The dried fibers are then cut into short fibers and sterilized after non-woven fabric processing.

[0020] Preferably, the alginate multifunctional layer is a bioactive glass / chitosan / alginate dressing, which is prepared by the following method:

[0021] (a) Take 12.5g TEP, 8.5g CN, and 1.46g TEOS. Add TEOS and TEP dropwise to a hydrochloric acid aqueous solution in sequence, stirring for 1 hour after each addition. Then add solid CN in multiple portions, stirring continuously to ensure complete hydrolysis of the precursor. Stop stirring when the solution becomes transparent and homogeneous. Allow the resulting sol solution to age at room temperature for 3 days. Dry the gel at 60℃ and 120℃ for 3 days each. Place the dried gel in a high-temperature sintering furnace for sintering. Load the resulting sintered product, agate grinding balls, and anhydrous ethanol into a ball mill jar at a mass ratio of 1:3:1 and ball mill. After ball milling, dry the milling liquid in a 120℃ oven for one day. Sieve the resulting powder through a 20-50 micrometer standard sieve to obtain SGBG powder. Mix the SGBG powder with a solid-liquid ratio of 80-150g / 200-500ml. The powder was dispersed in acetone and subjected to ultrasonic vibration and mechanical stirring to obtain a bioactive glass dispersion.

[0022] (b) Prepare an acetic acid aqueous solution containing chitosan, wherein the mass ratio of chitosan to the volume of the acetic acid aqueous solution is 1~3g:100mL; mix the acetic acid aqueous solution containing chitosan and an aqueous solution of sodium alginate evenly, wherein the mass fraction of acetic acid in the acetic acid aqueous solution is 1%, and the aqueous solution of sodium alginate is prepared by mixing sodium alginate and ultrapure water, wherein the mass ratio of sodium alginate to the volume of ultrapure water is 0.5~1.5g:50mL; then add an aqueous solution of bioactive glass suspension to obtain a mixture, wherein the bioactive glass suspension is prepared by mixing bioactive glass and ultrapure water, wherein the mass ratio of bioactive glass to the volume of ultrapure water is 0.2~0.6g:2mL;

[0023] (c) The spinning solution of sodium alginate is used to make yarn. After the yarn is drawn and washed, it is immersed in a solution or suspension containing drugs that promote wound healing. Then it is dried, wound and cut into sodium alginate fibers. The sodium alginate fibers are opened, combed and needle-punched or hydroentangled with or without cross-laying to obtain the final product.

[0024] As a preferred option, the sintering conditions in step A) are: heating rate of 1℃ / min; holding at 350℃ and 600℃ for 120min each during the heating process from room temperature to 600℃; and ball milling parameters of 672rpm / min for 4h.

[0025] Preferably, the alginate multifunctional layer is a copper-containing mesoporous bioactive glass / honey / alginate dressing, which is prepared by the following method:

[0026] (a) 6.92g Pluronic F108 was dissolved in 36.2ml ethanol in a 40℃ water bath to obtain solution I. 2.48g Ca(NO3)24H2O, 0.637g TEP, 11.66g TEOS, 1.9ml 1M HCl, 15.24ml ethanol and 5.72ml H2O were thoroughly mixed under stirring to obtain solution II. Solution I and solution II were mixed in a container and stirred overnight in a 40℃ water bath. The sol was then poured into a petri dish and treated with EISA in a 40℃ room temperature water bath. The resulting gel was aged at 40℃ for 6 days. The collected dry gel was then calcined at 600℃ for 5 hours and then ground using a benchtop planetary ball mill to obtain fine MBGs powder.

[0027] (b) By weight, 50-100 parts of honey are de-crystallized and liquefied at 65-80℃, and then dehydrated at low temperature until the water content of the honey is 15%-25%. Then, 0.5-3 parts of synthetic borneol are added and stirred thoroughly. The mixture is then placed in a freeze dryer and freeze-dried at -40 to -10℃ for 12-36 hours to form solid honey. The solid honey layer is then pulverized into honey powder of 60-500 mesh.

[0028] (C) Fine MBGs powder was gradually added to distilled water, and the suspension was dispersed in an ultrasonic probe for 2 minutes. Honey was then added, and the honey / SA / PVA mixture was stirred at room temperature for 12 h to obtain a homogeneous solution. Separation solutions of 1.5% w / v CMC and alginate were prepared in distilled water. The two solutions were maintained at 50°C with magnetic stirring until the mixture was homogenized within 30 minutes. 5%, 7.5%, and 10% w / v glycerol were added to each solution, respectively. A 1% CaCl2 aqueous solution was prepared and added dropwise to the solution while the alginate solution was still being stirred and heated. After obtaining the two membrane solutions, they were mixed at a 1:1 mass ratio for 30 minutes with mechanical stirring at 900 rpm. The solution was then heated to 0.28 g / cm³. 2 The solution was poured into an acrylic plate under standard conditions and kept in a circulating air oven at 40°C for 24 hours. After the solution dried, the resulting dressing was soaked in an aqueous solution of 5% calcium chloride and 3% glycerin for 20 minutes. Then the dressing was washed in an aqueous solution of 3% glycerin for 1 minute.

[0029] Preferably, in step (a), the Si:Ca:P molar ratio of the MBGs fine powder is 80:15:5.

[0030] Preferably, in step A), solution II also contains hemi(pentahydrate)copper(II)nitrate, and the resulting MBGs fine powder has a Si:Cu:Ca:P molar ratio of 78:2:15:5 or 75:5:15:5.

[0031] Preferably, the anti-infection and healing-promoting alginate dressing is prepared by laminating an electrospun film and a nonwoven fabric using a temperature- and pressure-controlled lamination device. During the lamination process, the materials are arranged in the structural order of an antibacterial barrier layer, an alginate functional layer, and a one-way moisture-wicking layer. During the lamination process, the device is set to operate at a lamination temperature of 56°C and a pressure of 12N, and the lamination time is controlled at 40 seconds.

[0032] Preferably, the method for preparing the antimicrobial barrier layer can be replaced by the following method:

[0033] 1) Dissolve 3.6% PCL and 2.4% SA in TFE and stir continuously for 24 h. Add ICA and MXF at a mass ratio of 0.05 and 5 wt% respectively to the polymer solution and stir for 24 h to obtain electrospinning solutions containing the corresponding drugs. Assemble PCL / alginate membranes from the solutions containing ICA and MXF by electrospinning.

[0034] 2) The electrospinning solution containing ICA was added at 1.0 mL / h −1 The feed rate is achieved through a blunt needle; the voltage is 22 kV, the distance between the needle and the grounded mandrel is 20 cm, and the needle rotates at a speed of 500 rpm; the electrospinning is terminated after 4 h at 25°C, and the solution containing MXF is electrospinned again for 4 h under the same electrospinning parameters.

[0035] This invention provides an anti-infective and healing-promoting alginate dressing. This technical solution utilizes a multifunctional dressing combining alginate, PCL (polycaprolactone), bioactive glass, and nano-ZnO, possessing both anti-infective and healing-promoting functions. Alginate, as the main component, effectively absorbs and retains wound exudate due to its excellent water absorption and biocompatibility, maintaining a moist environment to promote healing. PCL, as a supporting structural material, not only enhances the dressing's mechanical strength and stability but also ensures comfort and long-term effectiveness during use. Bioactive glass, as an anti-infective and healing-promoting component, effectively inhibits pathogen growth and stimulates tissue regeneration. This innovative formulation design not only focuses on the interaction and optimization of functional materials but also achieves an optimal balance between anti-infective and healing-promoting functions through structural design.

[0036] Regarding the composite process of the various materials, this invention prepares a three-layer material (antibacterial barrier membrane: PCL + alginate, alginate dressing, and one-way moisture-wicking layer: PCL) using electrospinning technology, and then composites them using a hot-pressing process. Hot pressing not only ensures good adhesion and bonding between the layers but also guarantees the structural stability and functional integrity of the final product. Through this composite process, an innovative multifunctional alginate dressing is realized.

[0037] Furthermore, this invention effectively controls the porosity of the antibacterial barrier membrane. The barrier membrane, composed of PCL and alginate, aims to prevent the entry of external bacteria. Precise control of the electrospinning process parameters is necessary to minimize the pore size of the barrier membrane. Its primary purpose is to effectively block external bacteria, thereby reducing the risk of infection. Precise control of process parameters is crucial during the electrospinning preparation process to ensure the barrier membrane has the smallest possible pore size. To achieve precise control of pore size, key parameters such as the concentration of the spinning solution, the electric field strength, and the spinning speed need to be optimized. Higher solution concentrations and appropriate electric field strengths allow for finer and more tightly packed fibers, thereby reducing the pore size.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] 1. Innovative Multifunctional Application: Combining alginate dressings with bioactive glass to achieve dual functions of promoting healing and preventing infection.

[0040] 2. Drug-free dual-function dressing: The main body of the dressing uses drug-free ingredients to achieve the dual functions of promoting healing and fighting infection.

[0041] 3. Single-substance dual-function dressing: uses only the same substance to achieve both healing-promoting and infection-fighting functions. Attached Figure Description

[0042] Figure 1 This is a schematic diagram of the structure of the dressing of the present invention.

[0043] Figure 2 This is a flowchart illustrating the preparation process of sol-gel bioactive glass (BG-1) in this invention. Detailed Implementation

[0044] The specific embodiments of the present invention will be described in detail below. To avoid excessive and unnecessary detail, well-known structures or functions will not be described in detail in the following embodiments. The approximate language used in the following embodiments is for quantitative purposes, indicating that a certain degree of variation in quantity is permissible without changing the basic function. Unless otherwise defined, the technical and scientific terms used in the following embodiments have the same meaning as commonly understood by those skilled in the art to which this invention pertains.

[0045] An anti-infective and healing-promoting alginate dressing, such as Figure 1 As shown, it includes an antibacterial barrier layer, an alginate multifunctional layer, and a one-way moisture-wicking layer.

[0046] (1) Materials and preparation of antibacterial barrier layer

[0047] Preparation method 1 of PCL / alginate (SA) membrane:

[0048] 1. Preparation of SA / PCL emulsion

[0049] There are two methods for emulsion preparation: a two-step method, in which the dispersed phase is first prepared, added to a solvent containing a surfactant, and completely dispersed before adding the continuous polymer phase to dissolve and disperse again; and a one-step method, in which the dispersed phase and continuous phase are prepared separately, and then the dispersed phase is added to the continuous phase containing a surfactant and fully dispersed.

[0050] The one-step method is suitable for solutions with low viscosity, but due to the high viscosity of SA aqueous solution, it is difficult to disperse evenly. Therefore, this experiment uses a two-step method to prepare SA / PCL emulsion. First, SA is dissolved in deionized water to prepare an SA aqueous solution of a certain concentration, which is then allowed to stand to remove bubbles. Then, chloroform, SA aqueous solution, and Span80 are homogenized in a homogenizer at 7000 rpm for 15 min. Next, a certain mass of PCL is added (the ratio of PCL mass to SA aqueous solution volume is 1 g:1 ml, and the mass fraction of Span80 relative to PCL is 66%). The mixture is then placed in a constant-temperature shaker for continuous homogenization for 12 h until the PCL is completely dissolved. Finally, the homogenizer is homogenized again at 7000 rpm for 15 min to obtain the desired spinning emulsion.

[0051] 2. Preparation of SA / PCL composite fiber membrane by emulsion electrospinning

[0052] SA / PCL composite fiber membranes were prepared by electrospinning of the above solution or emulsion. The spinning solution flow rate was 0.65 ml / h, the spinning voltage was 10.5 kV, the receiving distance was 10 cm, the spinning ambient temperature was (25±5)℃, and the relative humidity was (60±5)%.

[0053] Method 2 for preparing PCL / alginate (SA) membranes:

[0054] 1. Preparation of SA / PCL emulsion

[0055] 3.6% PCL and 2.4% SA were dissolved in TFE and stirred continuously for 24 h. ICA and MXF were added to the polymer solution at mass ratios of 0.05 and 5 wt%, respectively, and stirred for 24 h to obtain electrospinning solutions containing the corresponding drugs. The solutions containing ICA and MXF were then assembled into PCL / alginate (SA) membranes via electrospinning.

[0056] 2. Preparation of SA / PCL composite fiber membranes by electrospinning

[0057] The electrospinning solution containing ICA was fed through a blunt needle at a rate of 1.0 mL h−1. The optimal voltage was 22 kV, the distance between the needle and the grounded mandrel was 20 cm, and the needle was rotated at a speed of 500 rpm. Electrospinning was terminated after 4 h at 25 °C. Under the same electrospinning parameters, the solution containing MXF was electrospinned for another 4 h, and the resulting product was labeled as SA / PCL composite fiber membrane.

[0058] 3. Characterization of SA / PCL composite fiber membrane

[0059] The morphology of the electrospun nanofiber membrane was characterized using a scanning electron microscope (SEM) (Hitachi S4800, Japan). One hundred pores formed between 100 randomly selected fibers and physically stacked fibers were analyzed using ImageJ software to obtain the average fiber diameter and the average pore size of the corresponding membrane layer, ensuring that the pore size was less than 1 μm to prevent bacteria and other contaminants from entering. The apparent density and porosity of the membrane were measured and calculated according to the methods described previously. The crystallization structure of MXF powder, ICA powder, and the electrospun fiber membrane was characterized using an X-ray diffractometer (D / Max, Rigaku, Japan), investigating the dispersion and crystallization of drugs within the nanofibers. X-ray diffraction (XRD) experiments were conducted at a scan rate of 10° min⁻¹, with a scan range of 5°–70°.

[0060] (2) Multifunctional materials and preparation of alginate

[0061] Preparation and performance study of bioactive glass / nano-ZnO / alginate dressing

[0062] 1. Preparation of bioactive glass by sol-gel method

[0063] Nanoscale bioactive glass (composed of 35CaO-60SiO2-5P2O5, mol%) was prepared using a sol-gel combined freeze-drying method. The experimental flowchart is shown in Figure 2. The specific experimental steps are as follows: 12.2 mL of LTEOS and 7.8 g of Ca(NO3)2·4H2O were added to a solution of 120 mL deionized water and 40 mL anhydrous ethanol. The pH of the solution was adjusted to approximately 2 with hydrochloric acid under high-speed stirring. Then, 1.3 g of (NH4)2HPO4 was dissolved in deionized water. After complete dissolution, a certain amount of polyethylene glycol (PEG-10000) was added and stirred thoroughly. The solution was then slowly poured into the above solution, and ammonia was added to adjust the pH to 10. The mixture was stirred for 48 h, and then aged in air for 24 h to obtain a white precipitate. The precipitate was freeze-dried in a freeze dryer and then heat-treated in a box furnace at 650°C to obtain nanoscale bioactive glass, denoted as BG. The absorption spectra of the samples were measured using Fourier transform infrared spectroscopy (FT-IR) to qualitatively analyze the composition of the materials. The microstructure was observed using field emission scanning electron microscopy (FES-SEM), and the chemical composition was determined using an elemental electron spectrometer (EDS) attached to the scanning electron microscope. The particle size and particle size distribution were determined using a laser particle size analyzer. Thermogravimetric-differential thermal analysis was performed using a differential scanning calorimeter to determine the sintering temperature of the bioactive glass. The structure of the micro- and nanomaterials was determined by XRD pattern analysis.

[0064] 2. Preparation and characterization of zinc oxide nanoparticles

[0065] Spherical ZnO nanoparticles were synthesized by mixing 0.1 M zinc acetate dihydrate and 0.025–0.2 M sodium hydroxide in methanol. During the synthesis, polyethylene glycol (PEG) was used as a surfactant, and the reaction mixture was vigorously stirred at room temperature for 20 min. The amount of PEG added per gram of ZnO was selected to achieve an approximate monolayer coverage on the 40 nm nanoparticles. Rough calculations indicate that this is equivalent to 0.1 g of PEG per gram of ZnO. Literature reports that PEG molecules are linked to ZnO via hydrogen bonds. In this example, the PEG molecular chain with an average molecular weight of 8000 has a chain length of *87 nm. The average surface area of ​​molecules of this length is approximately 19 nm. 2 The surface area of ​​a 40nm ZnO particle is approximately 500nm. 2Therefore, approximately 25 molecules of PEG are required to provide complete surface coverage. This equates to approximately 0.1 g of PEG per gram of ZnO. To remove byproducts (sodium acetate), the precipitate was washed several times with ethanol and deionized water, and then redispersed in deionized water using ultrasound. The UV absorption spectrum of nano-ZnO was measured in the 350–450 nm range using a PerkinElmer UV spectrophotometer. The average particle size of nano-ZnO was determined using NICOMP 380ZLS dynamic light scattering (DLS). X-ray diffraction (XRD) analysis was performed using a PANalyticalXPERTPRO to determine the characteristic peaks of nano-ZnO. Continuous analysis of the particles was performed at 2° intervals of 0.02.

[0066] 3. Hydrophobic modification of calcium alginate fiber

[0067] Based on the weight percentage, 2-5 parts by weight of sodium alginate, 0.5-1 parts by weight of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and 0.5-1 parts by weight of N-hydroxysuccinimide are added sequentially to 100-200 parts by weight of a phosphate buffer solution with a pH of 6-7 in a certain molar ratio. After stirring evenly, the solution is added to 50-100 parts by weight of a methanol solution containing dodecylamine. The mixture is stirred at room temperature for 12-24 hours, then precipitated with methanol, centrifuged, dissolved in distilled water, dialyzed for 48-96 hours, and freeze-dried to obtain hydrophobically modified sodium alginate.

[0068] 4. Wet spinning

[0069] Sodium alginate is completely dissolved in distilled water to form a 10%~15% alginate solution (spinning solution). The spinning solution is poured into a syringe, and the other end is connected to a nitrogen cylinder. Under nitrogen pressure, it is squeezed into a 5%~10% calcium chloride solution (coagulation bath). The gel-like fibers extracted from the coagulation bath are stretched, washed, wound, and dried to obtain calcium alginate fibers.

[0070] 5. Preparation of bioactive glass / nano-ZnO / alginate wound repair dressing

[0071] Bioactive powder was added to a mixture of water and ethanol (volume ratio 1:1) and the powder was uniformly dispersed to form a suspension. ZnO nanoparticles with a concentration of 0.5% were mixed with the suspension and uniformly dispersed. Hydrophobically modified calcium alginate fibers were immersed in saturated KMnO4 for 5-10 minutes, then washed with distilled water to obtain coarse-removed alginate fibers. The coarse-removed alginate fibers were immersed in the suspension and fully soaked. The suspension was then uniformly sprayed onto the fiber surface, followed by centrifugation to dehydrate. The resulting wet fibers were soaked in an ethanol solution, centrifuged to remove the ethanol, and air-dried naturally. Subsequently, they were vacuum-dried at 60-80℃. The dried fibers were then slit into short fibers, processed into nonwoven fabrics, and sterilized.

[0072] Preparation and performance study of bioactive glass (SGBG) / chitosan / alginate dressing

[0073] 1. Preparation of Sol-Gel Bioactive Glass (SGBG) Powder Solution

[0074] Prepare the hydrochloric acid (catalyst) aqueous solution required for the experiment under stirring conditions at room temperature. The molar percentage of the chemical composition of the prepared SGBG is: 60% SiO2, 36% CaO, 4% P2O5. Calculate the required volume or mass of triethyl phosphate (TEOS), tetraethyl orthosilicate (TEP), and calcium nitrate tetrahydrate (CN) as precursor raw materials for silicon, phosphorus, and calcium. For example, the precursors required to prepare 0.1 mol of bioactive glass are: 12.5 g TEP, 8.5 g CN, and 1.46 g TEOS. Slowly add TEOS and TEP dropwise to the hydrochloric acid aqueous solution in sequence. After the addition is complete, continue stirring for 1 hour. Then, slowly add solid CN to the solution in multiple portions. After the addition is complete, continue stirring the solution to ensure complete hydrolysis of the precursors. Stop stirring when the solution becomes transparent and homogeneous. The obtained sol solution was allowed to stand at room temperature for 3 days to allow the molecules in the sol solution to continue to undergo condensation reactions until gelation formed into large wet gels. The gels were then dried at 60℃ and 120℃ for 3 days each to remove the large amount of ethanol byproducts generated during the reaction. The dried gels were then placed in a high-temperature sintering furnace for sintering (sintering conditions: heating rate 1℃ / min; holding at 350℃ and 600℃ for 120 min each during the heating from room temperature to 600℃). The resulting sintered product, agate grinding balls, and anhydrous ethanol were loaded into a ball mill jar at a mass ratio of 1:3:1 and ball-milled (ball milling parameters: 672 rpm / min, 4 h). After ball milling, the milling liquid was placed in a 120℃ oven and dried for one day to remove the ethanol, obtaining smaller-scale bioactive glass particles. The obtained powder was sieved through a 20-50 micrometer standard sieve to obtain SGBG powder. Bioactive glass powder was dispersed in acetone at a solid-liquid ratio of 80-150 g / 200-500 mL, and ultrasonic vibration and mechanical stirring were applied simultaneously to obtain a bioactive glass dispersion.

[0075] X-ray diffraction (XRD) was used to characterize the crystal phase composition of SGBG powder, with a scan rate of 10° / min and a 2θ diffraction angle range of 10–70°. FTIR was used to characterize the chemical structure of the SGBG powder. Sample preparation was performed using a pelleting method, where the SGBG powder and KBr powder were ground uniformly at a ratio of 1:100, pressed into pellets, and dried. The resulting pellets were then ready for instrumental analysis. Field emission scanning electron microscopy (GeminiSEM) was used to observe the surface morphology of the SGBG powder particles. An appropriate amount of SGBG powder was ultrasonically dispersed in an ethanol solution, and the supernatant solution was dropped onto a sample stage with a copper sheet attached. After drying and gold sputtering, the sample stage was placed in the GeminiSEM for observation and imaging.

[0076] 2. Preparation of sodium alginate solution containing chitosan and bioactive glass (SGBG)

[0077] Prepare an acetic acid aqueous solution containing chitosan (the mass ratio of chitosan to the volume of the acetic acid aqueous solution is (1~3) g: 100 mL); mix the acetic acid aqueous solution containing chitosan and the sodium alginate aqueous solution evenly (the mass fraction of acetic acid in the acetic acid aqueous solution is 1%; the sodium alginate aqueous solution is prepared by mixing sodium alginate and ultrapure water, and the mass ratio of sodium alginate to the volume of ultrapure water is (0.5~1.5) g: 50 mL); then add the bioactive glass suspension aqueous solution to obtain a mixture (the bioactive glass suspension is prepared by mixing bioactive glass and ultrapure water; the mass ratio of bioactive glass to the volume of ultrapure water is (0.2~0.6) g; 2 mL).

[0078] 3. Preparation of bioactive glass (SGBG) / chitosan / alginate dressing

[0079] Sodium alginate is used to make yarn. After the yarn is drawn and washed, it is immersed in a solution or suspension containing wound healing drugs. Then it is dried, wound and cut into sodium alginate fibers. The sodium alginate fibers are opened, combed and needled or hydroentangled with or without cross-laying to obtain the sodium alginate dressing.

[0080] ATR-FTIR was used to detect sodium alginate fibers with different SGBG doping contents to qualitatively analyze whether SGBG powder was successfully incorporated into the fibers. Simultaneous thermal analysis was used to detect the thermal stability of the fibers and the actual SGBG content. Test conditions (atmosphere: air; heating rate: 10℃ / min; heating range: 30℃ to 700℃). Fibers containing SGBG powder were immersed in human body fluid (SBF) for 12 hours, 1 day, 3 days, and 5 days, respectively. After centrifugation of the immersion liquid, the supernatant was collected, and the concentrations of Ca, Si, and P ions in the extract were determined using ICP-AES.

[0081] Preparation and performance study of copper-containing mesoporous bioactive glass / honey / alginate dressing

[0082] 1. Synthesis and material characterization of Cu-MBGs

[0083] Synthesis of MBGs (SiO2-CaO-P2O5-CuO): After certain modifications, MBGs were synthesized using the EISA method. Tetraethyl orthosilicate (TEOS), triethyl phosphate (TEP), calcium nitrate tetrahydrate, and copper nitrate hemihydrate (II) were dissolved in ethanol / water to form a sol. Pluronic F108 was added to the sol as a structure-directing agent using hydrochloric acid as a catalyst. In a typical synthesis, 6.92 g of F108 (Mw=14600, Sigma) was dissolved in 36.2 ml of ethanol (99.9%) in a 40 °C water bath to obtain solution (I). 2.48 g of Ca(NO3)24H2O, 0.637 g of TEP (99.8%), 11.66 g of TEOS, 1.9 ml of 1M HCl, 15.24 ml of ethanol, and 5.72 ml of H2O were thoroughly mixed under stirring to obtain solution (II). Solution (I) and solution (II) were mixed in a bottle and stirred overnight in a water bath at 40°C. The sol was then poured into a petri dish and subjected to EISA treatment in a room temperature water bath at 40°C. The resulting gel was aged at 40°C for 6 days. The collected dry gel was then calcined at 600°C for 5 hours to remove the structure-directing agent and nitrates. The resulting sample was designated MBGSi80 (molar ratio Si / Ca / P = 80 / 15 / 5). MBGSi78Cu2 (molar ratio Si / Cu / Ca / P = 78 / 2 / 15 / 5) and MBGSi75Cu5 (molar ratio Si / Cu / Ca / P = 75 / 5 / 15 / 5) were synthesized with the same Ca / P molar ratio as MBGSi80, but the molar amounts of TEOS and Cu(NO3)22.5H2O were adjusted to match the set proportion of CuO substitution in the glass composition. After calcination, all MBGs were ground using a benchtop planetary ball mill (MinMill, Philips) to obtain fine MBG powder.

[0084] Powder X-ray diffraction (XRD) was performed using a position-sensitive Huber G670 detector and copper Ka1 radiation (k = 1.54060 Å). The morphology was characterized using transmission electron microscopy (TEM); a JEM-1400Plus (JEOL, Peabody, MA) operating at 120 kV was used. Small-angle X-ray scattering (SAXS) was performed on a Kratky compact small-angle system (Hecus, Austria). This system was equipped with a position-sensitive detector (PSD50M) consisting of 1024 channels, each with a width of 55.5 lm. The structural properties of the MBGs were determined using an ASAP2010 absorber (Micrometrics Co, Norcross, GA) at 77 K via N2 physical adsorption. Specific surface area and pore size distribution were determined using the Brunauer-Emmet-Teller (BET) and Barrett-Joyner-Halenda (BJH) methods, respectively. The total pore volume was calculated when the amount of adsorbed nitrogen was P / P0 = 0.98.

[0085] 2. Preparation of Honey Powder

[0086] By weight, 50-100 parts of honey are decrystalline and liquefied at 65-80°C, and then dehydrated at low temperature until the moisture content of the honey is 15%-25%. Then, 0.5-3 parts of synthetic borneol are added and stirred thoroughly. The mixture is then placed in a freeze dryer and freeze-dried at -40 to -10°C for 12-36 hours to form solid honey. The solid honey layer is then pulverized into honey powder of 60-500 mesh.

[0087] 3. Preparation of functional alginate dressings

[0088] The reagents used were sodium alginate (Exodo-Científica, 90.8–106%), anhydrous calcium chloride (Neon-96%–101%), sodium carboxymethyl cellulose (Dinamica-100%), and double-distilled glycerol (MV-Química, USP grade). The concentration used in the dressing was determined to be 100 mg / ml based on the lowest bactericidal concentration results for bioactive glass.

[0089] First, Cu-MBGs were gradually added to distilled water, and the suspension was dispersed in an ultrasonic probe (Ecosonics) for 2 minutes. A certain volume of honey was added to the Cu-MBGs solution to determine the honey concentration (0%, 5%, 10%, 15%, 20% (v / v)). Subsequently, the honey / SA / PVA mixture was stirred at room temperature for 12 h to obtain a homogeneous solution.

[0090] Separate solutions of 1.5% (w / v) CMC and alginate were prepared in distilled water. Both solutions were maintained at 50 °C with magnetic stirring (Fisatom) until the mixture was homogenized within 30 minutes. Glycerin was added to each solution at 5%, 7.5%, and 10% (w / v), respectively. Glycerin, as a plasticizer, is essential for obtaining soft dressings. At low concentrations, it results in brittle dressings, while at high concentrations, it promotes high elasticity. However, it has a viscous appearance, making it difficult to handle. A 1% aqueous solution of CaCl2 (0.05 g calcium chloride per 1 g alginate) was prepared and added dropwise to the solution while it was still being stirred and heated.

[0091] After obtaining the two membrane solutions, they were mixed at a 1:1 ratio (by mass) for 30 minutes with mechanical stirring at 900 rpm using a marine propeller (Fisatom). The solutions were then poured into acrylic plates under standard conditions of 0.28 g / cm² and kept in a circulating air oven (CIENLAB) at 40°C for 24 hours.

[0092] After the solution dries, the resulting dressing requires a second step: cross-linking. It is soaked in an aqueous solution of 5% calcium chloride and 3% glycerol for 20 minutes; then the dressing is washed in a 3% glycerol aqueous solution for 1 minute. Once the optimal glycerol concentration is determined, new functional dressings are prepared using the previous method, but with variations in the CaCl2 content in the solution, using the amounts previously described: 25%, 50%, and 75%. This reagent is related to the stiffness, tensile strength, and deformation of the dressing.

[0093] (3) Materials and preparation of one-way moisture-wicking layer

[0094] 1. Preparation of PCL solution

[0095] PCL (Mw≈80000 g / mol) was purchased from Sigma-Aldrich, USA. Medical-grade acetone was purchased from Nanjing Baker Trading Co., Ltd. (Nanjing, China). All solvents were analytical grade and required no further purification. PCL was dissolved in medical-grade acetone at a mass ratio of 1:4 and the solution was obtained by stirring with a magnetic stirrer at room temperature for 4 hours.

[0096] 2. Spinning parameters for electrospinning

[0097] During electrospinning, the solution was poured into 5 ml syringes and sequentially installed on the electrospinning apparatus. A blue needle with an inner diameter of 0.41 mm was used, the spinning voltage was 15 kV, the flow rate was 1 mL / h, the distance between the needle and the collector was 15 cm, and a rotating roller at 300 rpm was used as the collector. The prepared sample was dried in a drying oven and then stored at 4 ℃.

[0098] 3. Characterization of PCL membrane

[0099] The morphology of the material was characterized using a scanning electron microscope (Gemini SEM 300, Carl Zeiss AG), and the average diameter of the obtained fibers was analyzed using a nanometer. The organic composition of the fibers was determined using Fourier transform infrared spectroscopy (FTIR, Thermo Scientific Nicolet iN10), and the hydrophobicity of the material was measured using a static contact angle meter (WCA, SA100). Its thermal stability was determined using a thermogravimetric analyzer (TGA, TA-Q500).

[0100] (4) Hot pressing combination process

[0101] During the lamination of electrospun film and nonwoven fabric using a temperature- and pressure-controlled lamination device, the materials are arranged in a structural sequence of "antibacterial barrier layer, alginate functional layer, and one-way moisture-wicking layer." The lamination process is conducted at a lamination temperature of 56°C and a pressure of 12N. This temperature and pressure setting ensures effective bonding of the three layers without burning, while maintaining the inherent properties of the materials. The lamination time is controlled at 40 seconds to ensure sufficient fusion at the interfaces between the materials, preventing performance degradation due to excessive lamination time.

[0102] The embodiments of the present invention have been described in detail above, but the content described is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the scope of the present invention should be included within the protection scope of the present invention.

Claims

1. An anti-infective and healing-promoting alginate dressing, characterized in that, Includes an antibacterial barrier layer, an alginate multifunctional layer, and a one-way moisture-wicking layer; The antimicrobial barrier layer is prepared by the following method: 1) Dissolve SA in deionized water to prepare an SA aqueous solution of a certain concentration, and let it stand to remove bubbles for later use; homogenize chloroform, SA aqueous solution and Span80 at 7000 r / min for 15 min in a homogenizer, then add PCL and place in a constant temperature shaker for continuous homogenization for 12 h until PCL is completely dissolved. Then homogenize again at 7000 r / min for 15 min to obtain the spinning emulsion; wherein, the mass ratio of PCL to the volume of SA aqueous solution is 1 g: 1 ml, and the mass fraction of Span80 relative to PCL is 66%; 2) The emulsion was electrospun to prepare SA / PCL composite fiber membrane; wherein the spinning solution flow rate was 0.65 ml / h, the spinning voltage was 10.5 kV, the receiving distance was 10 cm, the spinning environment temperature was 25±5℃, and the relative humidity was 60±5%. The unidirectional moisture-wicking layer is prepared by the following method: A) PCL was dissolved in medical acetone at a mass ratio of 1:4, and the solution was obtained by stirring with a magnetic stirrer at room temperature for 4 hours. B) Electrospinning was performed on the sample. During the electrospinning process, the solution was poured into 5ml syringes and then installed on the electrospinning equipment. A needle with an inner diameter of 0.41mm was used, the spinning voltage was 15 kV, the flow rate was 1mL / h, the distance between the needle and the collector was 15cm, and a rotating drum at 300rpm was used as the collector. The obtained sample was dried in a drying oven and then stored in a refrigerator at 4℃. The alginate multifunctional layer is a bioactive glass / nano-ZnO / alginate dressing, which is prepared by the following method: (a) Add 12.2 mL of LTEOS to a solution of 120 mL deionized water and 40 mL anhydrous ethanol. 7.8gCa(NO3)2·4H2O The pH of the solution was adjusted to 1.8-2.2 with hydrochloric acid while stirring, and then 1.3g of... (NH4)2HPO4 Dissolved in deionized water, polyethylene glycol was added after complete dissolution and stirred thoroughly. The mixture was then poured into the above solution and ammonia was added to adjust the pH to 10. The mixture was stirred for 48 hours and then aged in air for 24 hours to obtain a white precipitate. The precipitate was placed in a freeze dryer for freeze drying and then placed in a box furnace for heat treatment at a sintering temperature of 650℃ to obtain nanoscale bioactive glass. (b) Spherical ZnO nanoparticles were synthesized by mixing 0.1M zinc acetate dihydrate and 0.025-0.2M sodium hydroxide in methanol. During the synthesis, polyethylene glycol was used as a surfactant, and the reaction mixture was stirred at room temperature for 20 min. The amount of PEG added was 0.08-0.12 g of PEG per gram of ZnO. The precipitate was washed several times with ethanol and deionized water, and then redispersed in deionized water by ultrasound. (C) By weight, 2-5 parts of sodium alginate, 0.5-1 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and 0.5-1 parts of N-hydroxysuccinimide are added sequentially to 100-200 parts of a phosphate buffer solution with a pH of 6-7 in a certain molar ratio. After stirring evenly, the solution is added to 50-100 parts of a methanol solution containing dodecylamine. The mixture is stirred at room temperature for 12-24 hours, then precipitated with methanol, centrifuged, dissolved in distilled water, dialyzed for 48-96 hours, and freeze-dried to obtain hydrophobically modified sodium alginate. (D) Sodium alginate is completely dissolved in distilled water to form a 10%~15% alginate solution as a spinning solution. The spinning solution is poured into a syringe, and the other end is connected to a nitrogen cylinder. Under nitrogen pressure, a 5%~10% calcium chloride solution is squeezed into the coagulation bath. The gel-like fibers extracted from the coagulation bath are stretched, washed, wound, and dried to obtain calcium alginate fibers. (e) Bioactive glass is added to a mixture of water and ethanol, and the powder is uniformly dispersed to form a suspension, wherein the volume ratio of water to ethanol in the mixture is 1:1; 0.5% ZnO nanoparticles are combined and mixed with the suspension to ensure uniform dispersion; hydrophobically modified calcium alginate fibers are immersed in saturated water. KMnO4 The alginate fibers are then washed with distilled water for 5-10 minutes to obtain coarse alginate fibers. The coarse alginate fibers are then immersed in a suspension and fully soaked. The suspension is then evenly sprayed onto the fiber surface and centrifuged to remove water. The resulting wet fibers are then soaked in an ethanol solution, centrifuged to remove the ethanol, and air-dried naturally. Subsequently, they are vacuum dried at 60-80℃. The dried fibers are then cut into short fibers and sterilized after nonwoven fabric processing. This anti-infective and healing-promoting alginate dressing is prepared by laminating an electrospun film and a nonwoven fabric using a temperature- and pressure-controlled lamination device. During the lamination process, the materials are arranged in the structural order of an antibacterial barrier layer, an alginate functional layer, and a one-way moisture-wicking layer. During the lamination process, the device is set to operate at a lamination temperature of 56°C and a pressure of 12N, with the lamination time controlled at 40 seconds.

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