An antibacterial dressing and its preparation method

Abstract

This invention discloses a method for preparing an antibacterial dressing, belonging to the field of medical dressing preparation technology. The invention involves dissolving dopamine hydrochloride in a Tris-HCl buffer solution and adding a hydrophilic modifier to obtain a modified dopamine antibacterial agent; then preparing a silver nanoparticle dispersion using a silver-derived compound; mixing the two in a specific ratio to form a composite antibacterial solution, which is then processed into antibacterial microcapsules using a complex coagulation method; subsequently, preparing a chitosan-silk fibroin surface film-forming solution and a composite antibacterial intermediate layer precursor solution containing a pore-forming agent; forming the surface and intermediate layers through fixed-thickness coating, drying, and freeze-drying; and finally, combining this with a highly breathable bottom layer to obtain the antibacterial dressing. This invention achieves highly efficient and broad-spectrum antibacterial action against common pathogens in wounds by constructing a synergistic antibacterial system of modified dopamine and silver nanoparticles; utilizes a complex coagulation microencapsulation process to achieve long-term controlled release of antibacterial components, avoiding the cytotoxicity of sudden silver ion release; and balances high absorbency and high breathability of the dressing through hydrophilic modification and pore-forming agent regulation.

Description

Technical Field

[0001] This invention relates to the field of medical dressing preparation technology, specifically to an antibacterial dressing and its preparation method. Background Technology

[0002] Antibacterial dressings, as core medical materials for wound care, effectively inhibit bacterial growth, absorb exudate, and create a suitable healing environment. They play an irreplaceable role in the treatment of infected wounds such as burns, ulcers, and postoperative wounds. Currently, there are many types of antibacterial dressings on the market. Among them, silver-based antibacterial dressings are widely used due to their broad antibacterial spectrum. However, single-silver-based dressings have problems such as rapid release of silver ions, excessively high local concentrations leading to cytotoxicity, and the tendency of silver nanoparticles to aggregate, reducing antibacterial sites and limiting antibacterial efficiency and long-term effectiveness. While natural polymer dressings have excellent biocompatibility, their antibacterial properties are weaker, making it difficult to control severe infections.

[0003] Meanwhile, existing dressings generally suffer from the technical flaw of struggling to balance absorbency and breathability. Some dressings employ a dense structure to enhance absorbency, resulting in poor breathability, which can cause the wound to become stuffy and hot, promoting anaerobic bacteria growth and delaying healing. On the other hand, some breathable dressings lack sufficient absorbency and cannot effectively remove wound exudate. Furthermore, the antibacterial components in traditional antibacterial dressings are often directly mixed in, making them prone to loss during use and hindering long-lasting antibacterial effects. Their poor adhesion to the dressing substrate further reduces their effectiveness.

[0004] Therefore, it is necessary to provide an antibacterial dressing and its preparation method to solve the above-mentioned technical problems. Summary of the Invention

[0005] The purpose of this invention is to provide an antibacterial dressing and its preparation method, in order to solve the technical problems of existing medical antibacterial dressings, such as low antibacterial efficiency, easy loss and uncontrolled release of antibacterial components, difficulty in balancing liquid absorption and breathability, and the fact that some dressings have cytotoxicity and poor biocompatibility, which cannot meet the technical requirements of efficient antibacterial and long-lasting wound care for infected wounds.

[0006] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides an antibacterial dressing, the antibacterial dressing having a three-layer composite structure, comprising, sequentially, a chitosan-silk fibroin modified surface layer, a composite antibacterial intermediate layer, and a highly breathable bottom layer; the composite antibacterial intermediate layer is loaded with antibacterial microcapsules containing modified dopamine antibacterial agent and silver nanoparticles, the antibacterial microcapsules having a biodegradable material as the capsule wall and a particle size of 1-5 μm; the thickness of the chitosan-silk fibroin modified surface layer is 0.1-0.3 mm, the thickness of the composite antibacterial intermediate layer is 0.3-0.8 mm, the thickness of the highly breathable bottom layer is 0.2-0.4 mm, and the total thickness of the three layers is 0.6-1.5 mm.

[0007] This invention uses chitosan-silk fibroin to construct the modified surface layer. Chitosan has natural antibacterial properties and can improve wound biocompatibility, while silk fibroin has excellent film-forming properties and wound adhesion. The combination of the two can reduce the adhesion between the dressing and the wound, while achieving preliminary antibacterial effect on the wound surface. The composite antibacterial intermediate layer serves as the core functional layer of the dressing, loading modified dopamine antibacterial agent and silver nanoparticles. It is the core carrier for achieving efficient antibacterial and liquid absorption, providing sufficient loading and space for the antibacterial components and porous structure to function. The highly breathable bottom layer uses polytetrafluoroethylene porous membrane or non-woven fabric, which relies on its high porosity to achieve rapid gas exchange and avoid the growth of anaerobic bacteria due to the hot and stuffy wound.

[0008] In a second aspect, the present invention provides a method for preparing an antibacterial dressing, comprising the following steps: (1) Preparation of modified dopamine antibacterial agent: Dopamine hydrochloride is dissolved in a weakly alkaline buffer solution with a pH of 8.0-8.5 to prepare a dopamine hydrochloride solution with a concentration of 2-5 mg / mL. A hydrophilic modifier is added, and the mixture is stirred continuously at a constant temperature of 25-35℃ for 4-8 h. After dialysis purification, centrifugation, and freeze drying, a powdered modified dopamine antibacterial agent is obtained. (2) Preparation of silver nanoparticle dispersion: Dissolve the silver source compound in deionized water to prepare a silver ion solution with a concentration of 0.5-2 mmol / L. Add a reducing agent to reduce in situ to generate silver nanoparticles with a particle size of 20-50 nm. Add a stabilizer and stir to inhibit particle aggregation and obtain silver nanoparticle dispersion. (3) Preparation of antibacterial microcapsules: Modified dopamine antibacterial agent and silver nanoparticle dispersion are mixed at a mass ratio of 1:2-1:4 to form a composite antibacterial solution. Biodegradable wall material is used as the capsule wall raw material. Antibacterial microcapsules are prepared by microencapsulation embedding process. After washing, centrifugation and drying, they are ready for use. (4) Preparation of chitosan-silk fibroin surface film-forming solution: Chitosan is dissolved in dilute acid solution and silk fibroin is dissolved in neutral buffer solution to form uniform solutions. The chitosan solution and silk fibroin solution are mixed at a mass ratio of 2:1 to 1:1 to obtain a mixed solution. A crosslinking agent is added to the mixed solution, stirred evenly and degassed under vacuum to obtain the surface film-forming solution. (5) Preparation of composite antibacterial intermediate layer precursor solution: Dissolve biocompatible polymer substrate in solvent to form porous scaffold precursor solution, add antibacterial microcapsules and disperse evenly, add pore-forming agent to adjust pore structure and degas, and obtain composite antibacterial intermediate layer precursor solution; (6) Three-layer composite molding: The surface film-forming liquid is coated with a thickness of 0.1-0.3 mm and dried to obtain a chitosan-silk fibroin modified surface layer. The composite antibacterial intermediate layer precursor liquid is coated with a thickness of 0.3-0.8 mm on the surface layer and freeze-dried to form a porous antibacterial scaffold layer. The high-permeability bottom layer is combined with the intermediate layer to make the three-layer structure tightly combined. (7) Post-processing: The composite dressing is washed, cross-linked and cured, and sterilized to finally obtain an antibacterial dressing.

[0009] This invention involves dissolving dopamine hydrochloride in a weakly alkaline buffer solution and adding a hydrophilic modifier for a isothermal reaction. The graft polymerization of the hydrophilic modifier alters the molecular structure of dopamine, enhancing its hydrophilicity and addressing the issues of dopamine's inherent strong hydrophobicity and tendency to aggregate. Subsequent dialysis purification, centrifugation, and freeze-drying remove reaction byproducts and unreacted raw materials, yielding a high-purity modified dopamine antibacterial agent. When preparing a silver nanoparticle dispersion by reducing a silver-derived compound, the addition of a stabilizer allows it to adsorb onto the surface of the silver nanoparticles, reducing interparticle aggregation forces, maintaining the dispersion of the silver nanoparticles, and ensuring effective exposure of their antibacterial sites. Finally, the modified dopamine antibacterial agent is mixed with the silver nanoparticle dispersion to prepare antibacterial microcapsules. The capsule wall encapsulates the antibacterial components, preventing them from flowing out during subsequent processes and use. The process involves several steps: first, the surface layer film-forming liquid is prepared by cross-linking agents to enhance its strength and stability; second, vacuum degassing removes air bubbles, ensuring the smoothness and density of the surface layer after formation; third, the addition of pore-forming agents creates a porous structure in subsequent processes, providing channels for liquid absorption and gas exchange, while ensuring uniform dispersion of antibacterial microcapsules in the substrate; and fourth, the three-layer composite molding process employs a fixed-thickness coating, drying, and freeze-drying process. Drying allows the surface film-forming liquid to form rapidly and ensures structural stability, while freeze-drying creates a uniform porous structure in the intermediate layer, avoiding structural collapse caused by conventional drying. Subsequent interlayer lamination ensures strong bonding between layers, preventing delamination during use.

[0010] Preferably, in step (1), the weakly alkaline buffer solution is a Tris-HCl buffer solution, the mass ratio of the hydrophilic modifier to dopamine hydrochloride is 1:3-1:5, the dialysis purification time is 24-48h, the centrifugation speed is 5000-8000r / min, the centrifugation time is 10-20min, the freeze-drying temperature is -40~-60℃, the vacuum degree is 10-30Pa, and the drying time is 12-24h; in step (1), the hydrophilic modifier is at least one of polyethylene glycol, carboxymethyl cellulose, or quaternary ammonium salt modified monomer.

[0011] This invention uses Tris-HCl buffer solution as the reaction medium, which has stable buffering capacity and can precisely maintain the pH of the reaction system within a weakly alkaline range of 8.0-8.5. This pH environment is suitable for the oxidative self-polymerization of dopamine and the graft polymerization with hydrophilic modifiers, ensuring effective grafting of the hydrophilic modifier to dopamine hydrochloride and improving modification efficiency. The mass ratio of hydrophilic modifier to dopamine hydrochloride of 1:3-1:5 ensures that the hydrophilic modifier fully participates in the reaction, achieving effective modification of dopamine molecules, improving their hydrophilicity and dispersibility in aqueous systems and substrates, while avoiding excessive coverage of the active groups of dopamine by the hydrophilic modifier, which would lead to a decrease in its antibacterial properties. Polyethylene glycol can introduce hydrophilic ether bonds to enhance the hydrophilicity and flexibility of dopamine. Carboxymethyl cellulose can increase the film-forming and liquid-absorbing properties of dopamine. Quaternary ammonium salt modified monomers can introduce quaternary ammonium groups to enhance the antibacterial properties of dopamine. The selection of various hydrophilic modifiers can achieve complementary and synergistic effects of different functions. Dialysis purification for 24-48 hours can gradually remove small molecule byproducts and unreacted inorganic salts in the reaction system through the permeation of a semi-permeable membrane. Centrifugal force can effectively separate the modified dopamine antibacterial agent from liquid phase impurities, improving product purity. Under vacuum and low temperature conditions, the water in the material directly sublimates into gas, which can avoid the agglomeration of modified dopamine antibacterial agent and destruction of active groups caused by conventional drying, ensuring the dispersibility and antibacterial activity of the product. At the same time, a loose powder structure is formed, which is convenient for subsequent mixing with silver nanoparticle dispersion.

[0012] Preferably, in step (2), the silver source compound is one of silver nitrate and silver chloride, the molar ratio of reducing agent to silver ions is 1:1-2:1, the reaction temperature is 20-30℃, the reaction time is 1-3h, the stabilizer concentration is 0.1-0.3mg / mL, and the stirring inhibition time is 30-60min; in step (2), the reducing agent is one of sodium citrate and sodium borohydride, and the stabilizer is one of polyvinylpyrrolidone and sodium citrate.

[0013] This invention selects silver nitrate and silver chloride as the silver source compounds. Both are water-soluble silver salts, capable of fully dissolving in deionized water to form a silver ion solution, providing a sufficient silver ion source for the in-situ reduction of silver nanoparticles. A molar ratio of reducing agent to silver ions of 1:1-2:1 ensures that silver ions are fully reduced to silver nanoparticles while avoiding residual impurities caused by excessive reducing agent. When sodium citrate is used as the reducing agent, the reduction product is a harmless sodium salt, and sodium citrate also acts as a partial stabilizer. Sodium borohydride has strong reducing power and can rapidly reduce silver ions to obtain silver nanoparticles with uniform particle size. The reaction temperature is 20-30℃, and the reaction time is 1-3 hours. This temperature range ensures the rate and stability of the reduction reaction, avoiding excessively high temperatures that could lead to rapid growth of silver nanoparticles. Agglomeration is prevented; if the temperature is too low, the reaction rate will be too slow, extending the preparation cycle. A reaction time of 1-3 hours can ensure complete reduction of silver ions while controlling the particle size of silver nanoparticles to 20-50 nm. A stabilizer concentration of 0.1-0.3 mg / mL ensures that stabilizer molecules are fully adsorbed on the surface of silver nanoparticles, forming a steric hindrance layer, effectively inhibiting the agglomeration and growth of silver nanoparticles, and maintaining their nanoscale particle size and dispersion state. Polyvinylpyrrolidone, as a stabilizer, has strong adsorption and stable binding force with silver nanoparticles, while sodium citrate has both reducing and stable properties and good compatibility with the system. Stirring inhibits agglomeration for 30-60 minutes. Continuous stirring allows the stabilizer to fully contact the silver nanoparticles, breaking the agglomeration tendency between particles and ensuring the stability of the silver nanoparticle dispersion.

[0014] Preferably, in step (3), the biodegradable wall material is at least one of gelatin, sodium alginate, and polylactic acid; the microencapsulation process is a complex coagulation method, and the specific steps are as follows: 3a) Preparation of wall material solution: Dissolve the biodegradable wall material in the corresponding solvent, stir until completely dissolved and evenly dispersed, and prepare a biodegradable wall material solution with a concentration of 5-10 wt% for later use; 3b) Dispersion of composite antibacterial liquid: The composite antibacterial liquid formed by mixing modified dopamine antibacterial agent and silver nanoparticle dispersion at a mass ratio of 1:2-1:4 is slowly added to the wall material solution prepared in step 3a), and stirred continuously at a stirring rate of 200-400 r / min for 15-20 min to form a primary emulsion system; 3c) Complex coagulation reaction: Adjust the pH of the primary emulsification system in step 3b) to 4.0-5.0, maintain the stirring rate in step 3b) unchanged, and react at room temperature for 30-60 min to form microcapsule prototypes; 3d) Curing and shaping: Heat the system containing the microcapsule prototype in step 3c) to 30-40℃, maintain this curing temperature, and continue stirring at a rate of 200-400 r / min for 1-2 h to complete the curing and shaping of the microcapsules and obtain the microcapsule system; 3e) Washing and purification: Centrifuge the microcapsule system obtained in step 3d) to remove the supernatant, and wash the microcapsule precipitate repeatedly with deionized water 2-3 times to obtain water-containing antibacterial microcapsules; 3f) Low-temperature drying: The water-containing antibacterial microcapsules obtained in step 3e) are placed in a low-temperature drying environment of 40-60℃ and dried for 2-4 hours to obtain dried antibacterial microcapsules with a particle size of 1-5μm.

[0015] This invention selects gelatin, sodium alginate, and polylactic acid (PLA) as biodegradable wall materials. Gelatin and sodium alginate are natural polymers with good biocompatibility and excellent film-forming properties, and can undergo re-coagulation under suitable pH conditions. PLA is a synthetic biodegradable polymer with high capsule wall strength, which can improve the structural stability of microcapsules. All three wall materials can gradually degrade in vivo without causing wound residue. A 5-10 wt% wall material solution is prepared; this concentration range ensures that the wall material solution has a suitable viscosity. If the viscosity is too low, it will not be effective. Effective coating of the composite antibacterial liquid into stable microcapsules is crucial. Excessive viscosity hinders dispersion, resulting in overly large and unevenly distributed microcapsule particles. Stirring at 200-400 rpm for 15-20 minutes ensures uniform dispersion of the composite antibacterial liquid into fine droplets within the wall material solution. The droplet size directly determines the subsequent microcapsule size. This process avoids excessive stirring speed leading to droplet breakage, while insufficient stirring speed results in uneven droplet dispersion. Adjusting the initial emulsification system to 4.0-5.0 allows the wall material to maintain its optimal performance. The molecules undergo charge reversal, increasing the electrostatic attraction between them and triggering a re-condensation reaction. This causes the wall material molecules to gradually coat the surface of the composite antibacterial droplets, forming microcapsule prototypes. Maintaining the same stirring rate at room temperature for 30-60 minutes ensures the re-condensation reaction proceeds fully, allowing the capsule walls to grow uniformly and initially solidify. Heating to 30-40℃ and stirring for 1-2 hours solidifies the capsules. Appropriate heating increases the degree of cross-linking of the wall material molecules, enhancing the mechanical strength and stability of the capsule walls and preventing damage to the microcapsules during subsequent washing and drying. After centrifugation, washing with deionized water 2-3 times removes unreacted wall material and impurities adsorbed on the microcapsule surface, improving microcapsule purity. Low-temperature drying at 40-60℃ for 2-4 hours slowly removes moisture from the microcapsules, ensuring the integrity of the capsule wall structure and preventing shrinkage, deformation, or rupture caused by high-temperature drying. Finally, antibacterial microcapsules with a particle size of 1-5 μm are obtained. This particle size ensures uniform dispersion of the microcapsules in the composite antibacterial intermediate layer substrate, while avoiding the impact of excessively large particle sizes on the porous structure and liquid absorption properties of the substrate.

[0016] Preferably, in step (4), the mass fraction of the dilute acid solution is 1-2%, the concentration of the chitosan solution is 1-3wt%, the pH of the neutral buffer solution is 7.0-7.4, the concentration of the silk fibroin solution is 2-4wt%, the amount of crosslinking agent added is 0.5-1.5% of the total mass of the mixed solution, and the vacuum degassing time is 10-20 min; in step (4), the dilute acid solution is dilute acetic acid or dilute hydrochloric acid, and the crosslinking agent is one of glutaraldehyde and genipin.

[0017] This invention uses a 1-2% (w / w) dilute acid solution to dissolve chitosan. Both dilute acetic acid and dilute hydrochloric acid are weak acids, which dissolve chitosan while avoiding degradation of the chitosan molecular chains caused by strong acids, thus preserving its film-forming and antibacterial properties. A concentration of 1-2% ensures complete dissolution of chitosan, forming a uniform chitosan solution, while avoiding excessively high acid concentrations that would lead to a low pH in the subsequent film-forming solution, affecting the cross-linking reaction. The chitosan solution concentration is 1-3 wt%, and the silk fibroin solution concentration is 2-4 wt%. This concentration range ensures that both solutions have suitable viscosity, forming a uniform and stable film-forming solution after mixing. Too low a concentration results in an overly thin film-forming solution, leading to uneven surface thickness and insufficient strength after forming; too high a concentration results in excessively viscous film-forming solution, making coating difficult. A neutral buffer solution with a pH of 7.0-7.4 ensures... During the dissolution process, silk fibroin maintains a stable molecular structure, preventing denaturation and loss of film-forming properties due to excessively high or low pH. A 2:1 to 1:1 mass ratio of chitosan solution to silk fibroin solution allows for complementary performance of the two polymer materials, ensuring the surface layer possesses excellent antibacterial, film-forming, and adhesion properties. The crosslinking agent is added at 0.5-1.5% of the total mass of the mixed solution, ensuring its full participation in the reaction and enhancing the structural strength, water resistance, and stability of the surface layer. This avoids excessive crosslinking agent leading to an overly hard and brittle surface, or insufficient crosslinking resulting in easy surface damage. A vacuum degassing time of 10-20 minutes completely removes air bubbles from the film-forming solution, ensuring a smooth, pinhole-free surface after coating and improving the overall performance of the surface layer. It is important to note that the degree of deacetylation of the chitosan is 75%-90%. This range ensures that the chitosan possesses good antibacterial activity, hydrophilicity, and film-forming properties, enabling it to form a stable cross-linked structure with silk fibroin while also providing preliminary antibacterial effects on the surface. The weight-average molecular weight of the silk fibroin is 60kDa-150kDa. This molecular weight range balances the solubility and film-forming strength of the silk fibroin. A molecular weight above 60kDa ensures structural stability and resistance to breakage after film formation, while a molecular weight below 150kDa ensures complete dissolution in neutral buffer solution, forming a homogeneous silk fibroin solution. When the molecular weight is below 60kDa, film-forming properties are poor and the surface is prone to cracking; when the molecular weight is above 150kDa, the solubility of the silk fibroin decreases, making it difficult to form a homogeneous solution and affecting the smoothness of the surface.

[0018] Preferably, in step (5), the concentration of the porous scaffold precursor solution is 5-10 wt%, the amount of antibacterial microcapsules added is 8-15% of the total mass of the porous scaffold precursor solution, the high-speed dispersion rate is 600-800 r / min, the dispersion time is 20-30 min, the mass ratio of the pore-forming agent to the polymer substrate is 1:2-1:4, the stirring time for adjusting the pore structure is 10-15 min, and the vacuum degassing time is 10-20 min.

[0019] In this invention, a porous scaffold precursor solution of 5-10 wt% is prepared. This concentration range ensures that the precursor solution has suitable viscosity and formability. If the concentration is too low, the intermediate layer structure after subsequent molding will be loose and lack strength; if the concentration is too high, the viscosity of the precursor solution will be too high, which is not conducive to the uniform dispersion of antibacterial microcapsules and the distribution of pore-forming agents. The amount of antibacterial microcapsules added is 8-15% of the total mass of the porous scaffold precursor solution. This amount ensures that the intermediate layer has sufficient antibacterial components to achieve efficient antibacterial activity, while avoiding the aggregation caused by excessive antibacterial microcapsules, which would affect the porous structure and liquid absorption performance of the substrate. Stirring at a high dispersion rate of 600-800 r / min for 20-30 min can ensure that the antibacterial microcapsules are uniformly dispersed in the porous scaffold precursor solution through high-speed shear force, avoiding the formation of antibacterial site blind areas by microcapsule aggregation. A dispersion time of 20-30 minutes ensures effective dispersion, allowing microcapsules to be evenly distributed within the substrate. A mass ratio of 1:2 to 1:4 between the porogen and the polymer substrate guarantees sufficient and uniformly distributed pores in subsequent processes, providing channels for liquid absorption and gas exchange. This avoids excessive porogen leading to a decrease in substrate structural strength, or insufficient pores affecting liquid absorption and gas permeability. Adjusting the stirring time to 10-15 minutes ensures uniform dispersion of the porogen in the precursor solution, guaranteeing a uniform distribution of pores and preventing excessive or insufficient pores in certain areas. A vacuum degassing time of 10-20 minutes removes air bubbles from the precursor solution, preventing them from forming large voids during subsequent molding, which could disrupt the uniformity of the porous structure of the intermediate layer and ensure its overall performance.

[0020] Preferably, in step (5), the biocompatible polymer substrate is at least one of polycaprolactone, polyethylene glycol, and hyaluronic acid, the solvent is one or a mixture of two of deionized water and ethanol, and the pore-forming agent is one of sodium chloride and mannitol.

[0021] This invention selects polycaprolactone, polyethylene glycol, and hyaluronic acid as biocompatible polymer base materials. Polycaprolactone possesses good mechanical properties and biodegradability, which can improve the structural stability of the intermediate layer; polyethylene glycol has strong hydrophilicity, which can improve the liquid absorption performance of the intermediate layer; hyaluronic acid has both good biocompatibility and liquid absorption, can be compatible with wound tissue, and can improve the liquid absorption capacity of the dressing. All three base materials are medical-grade biocompatible materials and will not irritate the wound. Deionized water, ethanol, or a mixture of the two solvents are selected according to the solubility of different base materials. The selection of solvents ensures that the substrate is fully dissolved to form a uniform porous scaffold precursor solution. Deionized water is an aqueous solvent with good biocompatibility, while ethanol is an organic solvent that can dissolve some hydrophobic substrates. The combination of the two can meet the dissolution requirements of different substrates. Sodium chloride and mannitol are selected as pore-forming agents. Both are water-soluble inorganic salts with biocompatibility. They can gradually dissolve during subsequent washing and use to form a connected porous structure without leaving residues in the substrate. At the same time, their crystal structures can form pores of uniform size, improving the liquid absorption and air permeability of the intermediate layer.

[0022] Preferably, in step (6), the coating thickness of the surface film-forming liquid is 0.1-0.3 mm, the drying temperature is 40-50℃, and the drying time is 2-4 h; in step (6), the coating thickness of the intermediate layer precursor liquid is 0.3-0.8 mm, the freezing rate is 5-10℃ / h, the temperature is lowered to -40~-60℃ and then kept warm for 2-4 h, the freeze-drying conditions are -40~-60℃, the vacuum degree is 10-30 Pa, and the drying time is 18-24 h; in step (6), the thickness of the high-permeability bottom layer is 0.2-0.4 mm, the composite method is hot-press composite or interface cross-linking composite, the hot-press composite temperature is 60-80℃, the pressure is 0.1-0.3 MPa, and the time is 10-20 min; in step (6), the high-permeability bottom layer is a polytetrafluoroethylene porous membrane or non-woven fabric with a porosity of 60-80% and a water vapor transmission rate of 2000-3000 g / (m 2 •24h).

[0023] In this invention, the surface film-forming liquid coating thickness is 0.1-0.3 mm, the drying temperature is 40-50℃, and the drying time is 2-4 hours. This low-temperature drying avoids the denaturation of chitosan and silk fibroin molecules caused by high temperatures, which would damage the film-forming properties and biocompatibility of the surface layer. The 2-4 hour drying time ensures sufficient removal of surface moisture, resulting in a stable and uniform surface structure after forming. The intermediate layer precursor liquid coating thickness is 0.3-0.8 mm, and the freezing rate is 5-10℃ / h. The slow freezing rate allows the moisture in the material to form uniform ice crystals. During subsequent freeze-drying, these ice crystals sublimate to form a porous structure with uniform size and interconnected distribution, avoiding excessively rapid freezing that would result in small and unevenly distributed ice crystals, affecting the porous structure performance. After cooling to -40~-60℃ and holding for 2-4 hours, the material is ensured to be completely frozen, preventing localized unglued areas that could lead to structural collapse during subsequent drying. The freeze-drying temperature is -40~-60℃, and the vacuum degree is 10-30P. a. Drying time: 18-24 hours. Under vacuum and low-temperature conditions, ice crystals directly sublimate into a gaseous state, preserving the porous structure of the material and ensuring the liquid absorption and air permeability of the intermediate layer. This also avoids substrate degradation and antibacterial microcapsule breakage caused by high-temperature drying. The high-permeability bottom layer has a thickness of 0.2-0.4 mm. Hot-pressing composite temperature: 60-80℃, pressure: 0.1-0.3 MPa, time: 10-20 minutes. This low-temperature hot-pressing ensures strong bonding between layers while preventing structural damage to the bottom and intermediate layers due to high temperatures. The 0.1-0.3 MPa pressure ensures tight adhesion between layers, preventing gaps. The 10-20 minute hot-pressing time guarantees the composite effect, ensuring a strong bond between the three layers. Interfacial cross-linking composite uses a cross-linking agent to chemically bond molecules between layers, improving interlayer bonding strength. The high-permeability bottom layer uses materials with a porosity of 60-80% and a water vapor permeability of 2000-3000 g / (m²). 2 A polytetrafluoroethylene porous membrane or nonwoven fabric (24h) with high porosity and water vapor permeability ensures rapid gas exchange and smooth water vapor discharge, preventing the wound from becoming hot and humid and creating a dry and breathable environment for wound healing.

[0024] Preferably, in step (7), the number of times of washing with deionized water is 2-3 times, the washing time for each time is 10-15 min, the crosslinking curing temperature is 50-60℃, and the curing time is 6-12 h; in step (7), the sterilization method is irradiation sterilization, and the irradiation dose is 20-30 kGy.

[0025] This invention removes unreacted raw materials, impurities, and pore-forming agents adsorbed on the surface and inside of the composite dressing by washing it 2-3 times with deionized water for 10-15 minutes each time, thereby improving the purity and biocompatibility of the dressing and preventing residual impurities from irritating the wound. The cross-linking curing temperature is 50-60℃, and the curing time is 6-12 hours. This temperature increases the degree of cross-linking of the polymer materials in the dressing, enhancing its overall structural strength, water resistance, and stability, and extending its service life. The 6-12 hour curing time ensures the cross-linking reaction proceeds fully while avoiding material degradation caused by prolonged high-temperature curing. Irradiation sterilization is employed, with an irradiation dose of 20-30 kGy. This ionization effect of radiation destroys the nucleic acid structure of bacteria, achieving sterilization without residue and without affecting the structure and performance of the dressing.

[0026] Compared with the prior art, the beneficial effects of the present invention are: 1. The antibacterial dressing prepared by this invention has high, broad-spectrum, and long-lasting controllable antibacterial efficacy. Specifically, it constructs a synergistic antibacterial system of modified dopamine antibacterial agent and silver nanoparticles. Modified dopamine achieves bacterial adsorption and cell membrane permeability disruption through the active effects of phenolic hydroxyl and amino groups, while silver nanoparticles destroy nucleic acid and enzyme activity by penetrating bacterial cells. The two mechanisms of action are complementary, significantly improving antibacterial efficiency and antibacterial spectrum coverage. At the same time, a complex coagulation microencapsulation process is used to encapsulate the composite antibacterial components with a biodegradable capsule wall, achieving slow and controlled release of antibacterial components, avoiding loss of antibacterial components and rapid release of silver ions, thus prolonging the antibacterial effect and ensuring biosafety.

[0027] 2. The antibacterial dressing prepared in this invention has synergistically optimized liquid absorption and breathability. Specifically, the hydrophilicity of the antibacterial components and the substrate is improved through graft polymerization of a hydrophilic modifier. At the same time, a pore-forming agent is introduced into the composite antibacterial intermediate layer to construct a connected porous structure, providing sufficient channels for liquid absorption and gas exchange. This achieves a balance between liquid absorption and breathability, which can absorb wound exudate in a timely manner while ensuring air circulation in the wound, avoiding the growth of anaerobic bacteria in a hot and humid environment, and creating a suitable microenvironment for wound healing.

[0028] 3. The antibacterial dressing prepared by this invention exhibits excellent biocompatibility and structural stability. Specifically, the surface layer utilizes a chitosan-silk fibroin composite system, leveraging the biocompatibility and wound adhesion of natural polymer materials to reduce adhesion and irritation between the dressing and the wound. The middle layer employs a medical-grade biocompatible polymer substrate, combined with biodegradable microcapsule wall material. The overall structural strength and water resistance of the dressing are enhanced through a cross-linking curing process. The interlayer bonding is ensured through hot-pressing or interfacial cross-linking composite methods, preventing delamination and damage during use and extending the service life. Attached Figure Description

[0029] Figure 1Line graph comparing the average antibacterial rates of the antibacterial dressings prepared in Examples 1-3 and Comparative Examples 1-6; Figure 2 Line graphs showing the liquid absorption rates of the antibacterial dressings prepared in Examples 1-3 and Comparative Examples 1-6; Figure 3 The bar chart shows the air permeability comparison of the antibacterial dressings prepared in Examples 1-3 and Comparative Examples 1-6. Figure 4 Line graphs showing the relative cell proliferation rate (RGR) of the antibacterial dressings prepared in Examples 1-3 and Comparative Examples 1-6. Detailed Implementation

[0030] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0031] Example 1 This embodiment provides a method for preparing an antibacterial dressing, the specific steps of which are as follows: 1. Preparation of modified dopamine antibacterial agent: Dopamine hydrochloride was dissolved in Tris-HCl buffer solution with pH 8.0 to prepare a dopamine hydrochloride solution with a concentration of 2 mg / mL. Polyethylene glycol was added, and the mass ratio of hydrophilic modifier to dopamine hydrochloride was 1:3. The reaction was carried out under constant temperature of 25℃ with continuous stirring for 4 h. After dialysis purification for 24 h, centrifugation at 5000 r / min for 10 min, and freeze drying at -40℃ and vacuum degree of 10 Pa for 12 h, a powdered modified dopamine antibacterial agent was obtained.

[0032] 2. Preparation of silver nanoparticle dispersion: Silver nitrate was dissolved in deionized water to prepare a silver ion solution with a concentration of 0.5 mmol / L. Sodium citrate was added, and the molar ratio of reducing agent to silver ions was 1:1. The in-situ reduction reaction was carried out at 20℃ for 1 h to generate silver nanoparticles with a particle size of 20 nm. 0.1 mg / mL polyvinylpyrrolidone was added and stirred for 30 min to inhibit particle aggregation, thus obtaining the silver nanoparticle dispersion.

[0033] 3. Preparation of antibacterial microcapsules: Modified dopamine antibacterial agent and silver nanoparticle dispersion were mixed at a mass ratio of 1:2 to form a composite antibacterial solution; gelatin was used as a biodegradable wall material and dissolved in deionized water to prepare a wall material solution with a concentration of 5wt%; the composite antibacterial solution was slowly added to the wall material solution and stirred continuously at a stirring rate of 200 r / min for 15 min to form a primary emulsion system; the pH value of the system was adjusted to 4.0, and the reaction was maintained at a stirring rate of 200 r / min at room temperature for 30 min to form microcapsule prototypes; the temperature was raised to 30℃ and maintained at this temperature, and stirred at 200 r / min for 1 h to complete the solidification and shaping; after centrifugation, the microcapsules were washed twice with deionized water; the water-containing antibacterial microcapsules were placed at a low temperature of 40℃ for 2 h to obtain dried antibacterial microcapsules with a particle size of 1 μm.

[0034] 4. Preparation of chitosan-silk fibroin surface film-forming solution: Chitosan with a degree of deacetylation of 75% was dissolved in 1wt% dilute acetic acid to prepare a 1wt% chitosan solution. Silk fibroin with a weight average molecular weight of 60kDa was dissolved in a neutral buffer solution with a pH of 7.0 to prepare a 2wt% silk fibroin solution. The two solutions were mixed at a mass ratio of 2:1. Glutaraldehyde was added at a mass ratio of 0.5% of the total mass of the mixed solution. The mixture was stirred evenly and vacuum degassed for 10 min to obtain the surface film-forming solution.

[0035] 5. Preparation of composite antibacterial intermediate layer precursor solution: Polycaprolactone was dissolved in ethanol to prepare a porous scaffold precursor solution with a concentration of 5wt%. Antibacterial microcapsules accounting for 8% of the total mass of the precursor solution were added. The solution was dispersed at high speed of 600r / min for 20min. Mannitol was added. The mass ratio of pore-forming agent to polymer substrate was 1:2. The solution was stirred for 10min to adjust the pore structure. Vacuum degassing was performed for 10min to obtain the composite antibacterial intermediate layer precursor solution.

[0036] 6. Three-layer composite molding: The surface film-forming solution is coated with a thickness of 0.1 mm and dried at 40℃ for 2 h to obtain a chitosan-silk fibroin modified surface layer; the composite antibacterial intermediate layer precursor solution is coated with a thickness of 0.3 mm on the surface layer, cooled to -40℃ at a freezing rate of 5℃ / h and held at that temperature for 2 h, and then freeze-dried at -40℃ under a vacuum of 10 Pa for 18 h to form a porous antibacterial scaffold layer; a 0.2 mm thick polytetrafluoroethylene porous membrane is hot-pressed with the intermediate layer at a temperature of 60℃, a pressure of 0.1 MPa, and a time of 10 min. The resulting polytetrafluoroethylene porous membrane has a porosity of 60% and a water vapor permeability of 2000 g / (m²). 2 •24h) to ensure the three-layer structure fits tightly together.

[0037] 7. Post-treatment: The composite dressing was washed twice with deionized water for 10 minutes each time, cross-linked and cured at 50°C for 6 hours, and then sterilized by 20kGy irradiation to finally obtain the antibacterial dressing.

[0038] The antibacterial dressing prepared in this embodiment has a total thickness of 0.6 mm across its three layers.

[0039] Example 2 This embodiment provides a method for preparing an antibacterial dressing, the specific steps of which are as follows: 1. Preparation of modified dopamine antibacterial agent: Dopamine hydrochloride was dissolved in Tris-HCl buffer solution with pH 8.3 to prepare a dopamine hydrochloride solution with a concentration of 3.5 mg / mL. Carboxymethyl cellulose was added, and the mass ratio of hydrophilic modifier to dopamine hydrochloride was 1:4. The reaction was carried out under constant temperature of 30℃ with continuous stirring for 6 h. After purification by dialysis for 36 h, centrifugation at 6500 r / min for 15 min, and freeze drying at -50℃ and vacuum degree of 20 Pa for 18 h, a powdered modified dopamine antibacterial agent was obtained.

[0040] 2. Preparation of silver nanoparticle dispersion: Silver chloride was dissolved in deionized water to prepare a silver ion solution with a concentration of 1.2 mmol / L. Sodium borohydride was added, and the molar ratio of reducing agent to silver ions was 1.5:1. The in-situ reduction reaction was carried out at 25℃ for 2 h to generate silver nanoparticles with a particle size of 35 nm. 0.2 mg / mL sodium citrate was added and stirred for 45 min to inhibit particle aggregation, thus obtaining the silver nanoparticle dispersion.

[0041] 3. Preparation of antibacterial microcapsules: Modified dopamine antibacterial agent and silver nanoparticle dispersion were mixed at a mass ratio of 1:3 to form a composite antibacterial solution; sodium alginate was used as a biodegradable wall material, and a wall material solution with a concentration of 7.5 wt% was prepared by dissolving it in deionized water. The composite antibacterial solution was slowly added to the wall material solution, and the mixture was stirred continuously at a stirring rate of 300 r / min for 18 min to form a primary emulsion system. The pH value of the system was adjusted to 4.5, and the mixture was stirred at a stirring rate of 300 r / min at room temperature for 45 min to form microcapsule prototypes. The temperature was raised to 35℃ and maintained at this temperature, and the mixture was stirred at 300 r / min for 1.5 h to complete the solidification and shaping. After centrifugation, the microcapsules were washed three times with deionized water. The water-containing antibacterial microcapsules were placed at 50℃ for low-temperature drying for 3 h to obtain dried antibacterial microcapsules with a particle size of 3 μm.

[0042] 4. Preparation of chitosan-silk fibroin surface film-forming solution: Chitosan with a degree of deacetylation of 82% was dissolved in 1.5wt% dilute hydrochloric acid to prepare a 2wt% chitosan solution. Silk fibroin with a weight average molecular weight of 100kDa was dissolved in a neutral buffer solution with pH 7.2 to prepare a 3wt% silk fibroin solution. The two solutions were mixed at a mass ratio of 1.5:1. Genipin was added at a mass of 1.0% of the total mass of the mixed solution. The mixture was stirred evenly and vacuum degassed for 15 min to obtain the surface film-forming solution.

[0043] 5. Preparation of composite antibacterial intermediate layer precursor solution: Polyethylene glycol was dissolved in a mixed solvent of deionized water and ethanol to prepare a porous scaffold precursor solution with a concentration of 7.5 wt%. Antibacterial microcapsules accounting for 12% of the total mass of the precursor solution were added, and the mixture was dispersed at a high speed of 700 r / min for 25 min. Sodium chloride was added, and the mass ratio of pore-forming agent to polymer substrate was 1:3. The mixture was stirred for 12 min to adjust the pore structure. Vacuum degassing was performed for 15 min to obtain the composite antibacterial intermediate layer precursor solution.

[0044] 6. Three-layer composite molding: A surface film-forming solution is coated with a thickness of 0.2 mm and dried at 45℃ for 3 hours to obtain a chitosan-silk fibroin modified surface layer; a composite antibacterial intermediate layer precursor solution is coated with a thickness of 0.5 mm onto the surface layer, cooled to -50℃ at a freezing rate of 8℃ / h and held at that temperature for 3 hours, and then freeze-dried at -50℃ under a vacuum of 20 Pa for 21 hours to form a porous antibacterial scaffold layer; a 0.3 mm thick nonwoven fabric is cross-linked with the intermediate layer interface, and the nonwoven fabric has a porosity of 70% and a water vapor permeability of 2500 g / (m²). 2 •24h) to ensure the three-layer structure fits tightly together.

[0045] 7. Post-treatment: The composite dressing was washed three times with deionized water for 12 minutes each time, cross-linked and cured at 55°C for 9 hours, and then sterilized by 25 kGy irradiation to finally obtain the antibacterial dressing.

[0046] The antibacterial dressing prepared in this embodiment has a total thickness of 1.0 mm across its three layers.

[0047] Example 3 This embodiment provides a method for preparing an antibacterial dressing, the specific steps of which are as follows: 1. Preparation of modified dopamine antibacterial agent: Dopamine hydrochloride was dissolved in Tris-HCl buffer solution with pH 8.5 to prepare a dopamine hydrochloride solution with a concentration of 5 mg / mL. Quaternary ammonium salt modified monomer was added. The mass ratio of hydrophilic modifier to dopamine hydrochloride was 1:5. The reaction was carried out under constant temperature of 35℃ with continuous stirring for 8 h. After purification by dialysis for 48 h, centrifugation at 8000 r / min for 20 min, and freeze drying at -60℃ and vacuum degree of 30 Pa for 24 h, a powdered modified dopamine antibacterial agent was obtained.

[0048] 2. Preparation of silver nanoparticle dispersion: Silver nitrate was dissolved in deionized water to prepare a silver ion solution with a concentration of 2 mmol / L. Sodium borohydride was added, and the molar ratio of reducing agent to silver ions was 2:1. The in-situ reduction reaction was carried out at 30℃ for 3 h to generate silver nanoparticles with a particle size of 50 nm. 0.3 mg / mL polyvinylpyrrolidone was added and stirred for 60 min to inhibit particle aggregation, thus obtaining the silver nanoparticle dispersion.

[0049] 3. Preparation of antibacterial microcapsules: Modified dopamine antibacterial agent and silver nanoparticle dispersion were mixed at a mass ratio of 1:4 to form a composite antibacterial solution; polylactic acid was used as a biodegradable wall material, and a 10wt% wall material solution was prepared by dissolving it in ethanol. The composite antibacterial solution was slowly added to the wall material solution, and the mixture was stirred continuously at a stirring rate of 400 r / min for 20 min to form a primary emulsion system. The pH of the system was adjusted to 5.0, and the mixture was stirred at a stirring rate of 400 r / min at room temperature for 60 min to form microcapsule prototypes. The temperature was raised to 40℃ and maintained at this temperature, and the mixture was stirred at 400 r / min for 2 h to complete the solidification and shaping. After centrifugation, the microcapsules were washed three times with deionized water. The aqueous antibacterial microcapsules were dried at a low temperature of 60℃ for 4 h to obtain dried antibacterial microcapsules with a particle size of 5 μm.

[0050] 4. Preparation of chitosan-silk fibroin surface film-forming solution: Chitosan with a degree of deacetylation of 90% was dissolved in 2wt% dilute acetic acid to prepare a 3wt% chitosan solution. Silk fibroin with a weight average molecular weight of 150kDa was dissolved in a neutral buffer solution at pH 7.4 to prepare a 4wt% silk fibroin solution. The two solutions were mixed at a mass ratio of 1:1. Genipin was added at a mass ratio of 1.5% of the total mass of the mixed solution. The mixture was stirred evenly and then degassed under vacuum for 20 minutes to obtain the surface film-forming solution.

[0051] 5. Preparation of composite antibacterial intermediate layer precursor solution: Hyaluronic acid was dissolved in deionized water to prepare a porous scaffold precursor solution with a concentration of 10wt%. Antibacterial microcapsules accounting for 15% of the total mass of the precursor solution were added and dispersed at high speed of 800r / min for 30min. Mannitol was added, and the mass ratio of pore-forming agent to polymer substrate was 1:4. The mixture was stirred for 15min to adjust the pore structure. Vacuum degassing was performed for 20min to obtain the composite antibacterial intermediate layer precursor solution.

[0052] 6. Three-layer composite molding: The surface film-forming solution is coated with a thickness of 0.3 mm and dried at 50℃ for 4 h to obtain a chitosan-silk fibroin modified surface layer; the composite antibacterial intermediate layer precursor solution is coated with a thickness of 0.8 mm on the surface layer, cooled to -60℃ at a freezing rate of 10℃ / h and held at that temperature for 4 h, and then freeze-dried at -60℃ under a vacuum of 30 Pa for 24 h to form a porous antibacterial scaffold layer; a 0.4 mm thick polytetrafluoroethylene porous membrane is hot-pressed with the intermediate layer at a temperature of 80℃, a pressure of 0.3 MPa, and a time of 20 min. The resulting polytetrafluoroethylene porous membrane has a porosity of 80% and a water vapor permeability of 3000 g / (m²). 2 •24h) to ensure the three-layer structure fits tightly together.

[0053] 7. Post-treatment: The composite dressing was washed three times with deionized water for 15 minutes each time, cross-linked and cured at 60°C for 12 hours, and then sterilized by 30 kGy irradiation to finally obtain the antibacterial dressing.

[0054] The antibacterial dressing prepared in this embodiment has a total thickness of 1.5 mm across its three layers.

[0055] Comparative Example 1 The only difference between this comparative example and Example 2 is that the composite antibacterial intermediate layer is not loaded with modified dopamine antibacterial agent, but only with silver nanoparticles. The rest of the preparation steps are completely the same as those in Example 2.

[0056] Expected performance: The synergistic antibacterial effect of unmodified dopamine antibacterial agent and silver nanoparticles is significantly reduced, and the silver nanoparticles are prone to agglomeration, making it impossible to achieve long-lasting antibacterial effect. At the same time, the dressing's ability to adsorb bacteria is weakened, making it difficult to quickly inhibit the reproduction of bacteria on the wound.

[0057] Comparative Example 2 The only difference between this comparative example and Example 2 is that the composite antibacterial intermediate layer is not loaded with silver nanoparticles, but only with modified dopamine antibacterial agent; the rest of the preparation steps are completely the same as in Example 2.

[0058] Expected performance: Without the rapid bactericidal effect of silver nanoparticles, relying solely on the bacteriostatic effect of modified dopamine antibacterial agents results in a slow overall antibacterial rate, making it difficult to quickly control wound infection and failing to meet the rapid antibacterial needs of infected wounds.

[0059] Comparative Example 3 The only difference between this comparative example and Example 2 is that no hydrophilic modifier was added when preparing the modified dopamine antibacterial agent; the rest of the preparation steps are completely consistent with Example 2.

[0060] Expected performance: The modified dopamine antibacterial agent has insufficient hydrophilicity, poor dispersibility in aqueous systems and dressing substrates, and is prone to agglomeration, resulting in uneven distribution of antibacterial sites and reduced antibacterial effect; at the same time, the overall hydrophilicity of the dressing is reduced, the liquid absorption capacity is greatly weakened, and it cannot absorb wound exudate.

[0061] Comparative Example 4 The only difference between this comparative example and Example 2 is that the antibacterial component was not encapsulated using a microencapsulation process, but was directly added to the composite antibacterial intermediate layer precursor solution. The remaining preparation steps are completely consistent with those of Example 2.

[0062] Expected performance: The antibacterial ingredients are not protected by the capsule wall and are easily lost during dressing preparation and use, making it impossible to achieve long-lasting antibacterial effect; moreover, silver ions are easily released rapidly, and excessively high local concentrations can easily cause cytotoxicity, reducing the biocompatibility of the dressing. At the same time, the antibacterial ingredients have poor adhesion to the substrate and are easily detached with wound movement.

[0063] Comparative Example 5 The only difference between this comparative example and Example 2 is that the pH value of the complex coagulation reaction was adjusted to 3.0 when preparing the antibacterial microcapsules; the rest of the preparation steps are completely consistent with Example 2.

[0064] Expected performance: If the pH value is too low, it deviates from the suitable range for coagulation reaction. The wall material cannot undergo sufficient coagulation reaction, resulting in poor microcapsule formation, thin and easily damaged capsule walls, inability to effectively encapsulate antibacterial components, easy leakage of antibacterial components, and uneven particle size distribution of microcapsules, making it difficult to disperse evenly in the dressing substrate and affecting the uniformity of antibacterial effect.

[0065] Comparative Example 6 The only difference between this comparative example and Example 2 is that no pore-forming agent was added to the composite antibacterial intermediate layer; the rest of the preparation steps are completely consistent with Example 2.

[0066] Expected performance: The dressing substrate has a porous structure without pore-forming agents, resulting in extremely low porosity and significantly reduced air permeability, which can easily lead to a hot and humid wound and the growth of anaerobic bacteria. At the same time, the substrate has insufficient liquid absorption channels, which significantly reduces its liquid absorption capacity and makes it unable to absorb wound exudate in time. Furthermore, the contact area between the antibacterial components and wound bacteria is reduced, resulting in a decrease in antibacterial effect.

[0067] To compare the performance differences of the preparation methods provided in Examples 1-3 and Comparative Examples 1-6, the present invention provides the following experimental methods: 1. Antibacterial rate test Referring to the shaking method in "Evaluation of Antimicrobial Properties of Antimicrobial Textiles" (GB / T20944.3-2008), Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (common pathogens on wounds) were selected as test strains, and a concentration of 1.0 × 10⁻⁶ was prepared. 5 ~1.0×10 6 The bacterial suspension was prepared at CFU / mL. Dressing samples were cut into 1cm × 1cm pieces and added to the suspension. The mixture was incubated at 37℃ with shaking for 24 hours. The viable count was calculated using the plate count method, and the inhibition rate was calculated using the following formula: Antibacterial rate (%) = (Number of viable bacteria in the blank group - Number of viable bacteria in the sample group) / Number of viable bacteria in the blank group × 100% 2. Liquid Absorption Rate Test Referring to the "Test Method for Liquid Absorption Performance of Medical Dressings" (YY / T0471.2-2020), the dressing sample was cut into 2cm×2cm dimensions, and the initial mass m0 was measured. The dressing was then immersed in deionized water at room temperature for 30 minutes until fully soaked. After immersion, the dressing was removed and hung until no liquid dripped. The mass m1 after absorption was measured, and the liquid absorption rate was calculated using the formula: Liquid absorption rate (%) = (m1 - m0) / m0 × 100% 3. Breathability test Referring to the "Determination of Air Permeability of Textile Fabrics" (GB / T5453-2025), an air permeability tester was used to test the air permeability of the dressing when the pressure difference was 100Pa. The unit is mm / s. The higher the air permeability value, the better the air permeability.

[0068] 4. Biocompatibility testing Referring to "Biological Evaluation of Medical Devices Part 5: In Vitro Cytotoxicity Tests" (GB / T16886.5-2017), the MTT assay was used to co-culture dressing extract with L929 mouse fibroblasts for 24 hours. The relative cell proliferation rate (RGR) was detected to evaluate the cytotoxicity level. An RGR ≥ 80% was considered to be non-cytotoxic.

[0069] The experimental data are as follows: Table 1. Results of antibacterial rate test (%)

[0070] Table 2 Results of liquid absorption rate and air permeability tests

[0071] Table 3. Biocompatibility test results (relative cell proliferation rate RGR, %)

[0072] Based on the experimental data in Tables 1-3 and Figures 1-4, it can be seen that the antibacterial dressings prepared in Examples 1-3 all exhibited good antibacterial effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, which are common pathogens in wounds. The average inhibition rates reached 99.92%, 99.96%, and 99.98%, respectively, achieving a near 100% antibacterial effect. Moreover, the antibacterial effect against different types of pathogens was uniform and stable. In contrast, the inhibition rates of Comparative Examples 1-6 all showed a significant decrease. Among them, Comparative Example 5 had an average inhibition rate of only 88.75% due to the pH value deviating from the suitable range during the coagulation reaction. Comparative Example 1, which was only loaded with silver nanoparticles, and Comparative Example 2, which was only loaded with modified dopamine, had average inhibition rates of 91.25% and 90.58%, respectively, which were far lower than the levels of the Examples. This directly reflects that the synergistic effect of modified dopamine antibacterial agent and silver nanoparticles achieved highly efficient antibacterial activity.

[0073] Regarding absorbency and air permeability, the absorbency rates of Examples 1-3 were 315%, 358%, and 392%, respectively, all significantly exceeding 300%, effectively absorbing wound exudate. Their air permeability was 82 mm / s, 95 mm / s, and 88 mm / s, respectively, maintaining a high level and effectively preventing wound congestion and anaerobic bacterial growth, thus meeting the core needs of infectious wound care. In contrast, the absorbency rates of the comparative examples all decreased to varying degrees. Comparative Example 6 (without pore-forming agent) and Comparative Example 3 (without hydrophilic modifier) ​​had absorbency rates of only 228% and 255%, respectively, the lowest among all samples. In terms of air permeability, only Comparative Example 6 showed a sharp drop in air permeability to 35 mm / s; the other comparative examples were not significantly different from the examples. This indicates that the addition of the hydrophilic modifier significantly improves the overall hydrophilicity of the dressing, and the porous structure constructed by the pore-forming agent is the key to increasing absorbency channels and ensuring gas exchange. Together, these two factors determine the high absorbency and high air permeability of the dressing.

[0074] Biocompatibility test results showed that the relative cell proliferation rate of Examples 1-3 was above 94.5%, with no cytotoxicity and excellent biocompatibility. Among the comparative examples, only Comparative Example 4, which did not use microencapsulation, resulted in the rapid release of silver ions due to the lack of capsule wall protection for the antibacterial components, causing the relative cell proliferation rate to drop to 76.5%, exhibiting mild cytotoxicity. The other comparative examples showed no cytotoxicity. This fully demonstrates that the complex coagulation microencapsulation process can effectively achieve slow and controlled release of antibacterial components, avoid excessively high local silver ion concentrations, thereby improving the biocompatibility of the dressing and ensuring safety in use.

[0075] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

Claims

1. An antibacterial dressing, characterized in that, The antibacterial dressing has a three-layer composite structure, comprising a chitosan-silk fibroin modified surface layer, a composite antibacterial intermediate layer, and a highly breathable bottom layer. The composite antibacterial intermediate layer is loaded with antibacterial microcapsules containing modified dopamine antibacterial agent and silver nanoparticles. The antibacterial microcapsules have a biodegradable material as the capsule wall and a particle size of 1-5 μm. The chitosan-silk fibroin modified surface layer has a thickness of 0.1-0.3 mm, the composite antibacterial intermediate layer has a thickness of 0.3-0.8 mm, and the highly breathable bottom layer has a thickness of 0.2-0.4 mm, with a total thickness of 0.6-1.5 mm.

2. A method for preparing the antibacterial dressing according to claim 1, characterized in that, Includes the following steps: (1) Preparation of modified dopamine antibacterial agent: Dopamine hydrochloride is dissolved in a weakly alkaline buffer solution with a pH of 8.0-8.5 to prepare a dopamine hydrochloride solution with a concentration of 2-5 mg / mL. A hydrophilic modifier is added, and the mixture is stirred continuously at a constant temperature of 25-35℃ for 4-8 h. After dialysis purification, centrifugation, and freeze drying, a powdered modified dopamine antibacterial agent is obtained. (2) Preparation of silver nanoparticle dispersion: Dissolve the silver source compound in deionized water to prepare a silver ion solution with a concentration of 0.5-2 mmol / L. Add a reducing agent to reduce in situ to generate silver nanoparticles with a particle size of 20-50 nm. Add a stabilizer and stir to inhibit particle aggregation and obtain silver nanoparticle dispersion. (3) Preparation of antibacterial microcapsules: Modified dopamine antibacterial agent and silver nanoparticle dispersion are mixed at a mass ratio of 1:2-1:4 to form a composite antibacterial solution. Biodegradable wall material is used as the capsule wall raw material. Antibacterial microcapsules are prepared by microencapsulation embedding process. After washing, centrifugation and drying, they are ready for use. (4) Preparation of chitosan-silk fibroin surface film-forming solution: Chitosan is dissolved in dilute acid solution and silk fibroin is dissolved in neutral buffer solution to form uniform solutions. The chitosan solution and silk fibroin solution are mixed at a mass ratio of 2:1 to 1:1 to obtain a mixed solution. A crosslinking agent is added to the mixed solution, stirred evenly and degassed under vacuum to obtain the surface film-forming solution. (5) Preparation of composite antibacterial intermediate layer precursor solution: Dissolve biocompatible polymer substrate in solvent to form porous scaffold precursor solution, add antibacterial microcapsules and disperse evenly, add pore-forming agent to adjust pore structure and degas, and obtain composite antibacterial intermediate layer precursor solution; (6) Three-layer composite molding: The surface film-forming liquid is coated with a thickness of 0.1-0.3 mm and dried to obtain a chitosan-silk fibroin modified surface layer. The composite antibacterial intermediate layer precursor liquid is coated with a thickness of 0.3-0.8 mm on the surface layer and freeze-dried to form a porous antibacterial scaffold layer. The high-permeability bottom layer is combined with the intermediate layer to make the three-layer structure tightly combined. (7) Post-processing: The composite dressing is washed, cross-linked and cured, and sterilized to finally obtain an antibacterial dressing.

3. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (1), the weakly alkaline buffer solution is a Tris-HCl buffer solution, the mass ratio of the hydrophilic modifier to dopamine hydrochloride is 1:3-1:5, the dialysis purification time is 24-48h, the centrifugation speed is 5000-8000r / min, the centrifugation time is 10-20min, the freeze-drying temperature is -40~-60℃, the vacuum degree is 10-30Pa, and the drying time is 12-24h; In step (1), the hydrophilic modifier is at least one of polyethylene glycol, carboxymethyl cellulose, or quaternary ammonium salt modifier.

4. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (2), the silver source compound is one of silver nitrate and silver chloride, the molar ratio of reducing agent to silver ions is 1:1-2:1, the reaction temperature is 20-30℃, the reaction time is 1-3h, the stabilizer concentration is 0.1-0.3mg / mL, and the stirring inhibition time is 30-60min; In step (2), the reducing agent is one of sodium citrate and sodium borohydride, and the stabilizer is one of polyvinylpyrrolidone and sodium citrate.

5. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (3), the biodegradable wall material is at least one of gelatin, sodium alginate, and polylactic acid; the microencapsulation process is a complex coagulation method, and the specific steps are as follows: 3a) Preparation of wall material solution: Dissolve the biodegradable wall material in the corresponding solvent, stir until completely dissolved and evenly dispersed, and prepare a biodegradable wall material solution with a concentration of 5-10 wt% for later use; 3b) Dispersion of composite antibacterial liquid: The composite antibacterial liquid formed by mixing modified dopamine antibacterial agent and silver nanoparticle dispersion at a mass ratio of 1:2-1:4 is slowly added to the wall material solution prepared in step 3a), and stirred continuously at a stirring rate of 200-400 r / min for 15-20 min to form a primary emulsion system; 3c) Complex coagulation reaction: Adjust the pH of the primary emulsification system in step 3b) to 4.0-5.0, maintain the stirring rate in step 3b) unchanged, and react at room temperature for 30-60 min to form microcapsule prototypes; 3d) Curing and shaping: Heat the system containing the microcapsule prototype in step 3c) to 30-40℃, maintain this curing temperature, and continue stirring at a rate of 200-400 r / min for 1-2 h to complete the curing and shaping of the microcapsules and obtain the microcapsule system; 3e) Washing and purification: Centrifuge the microcapsule system obtained in step 3d) to remove the supernatant, and wash the microcapsule precipitate repeatedly with deionized water 2-3 times to obtain water-containing antibacterial microcapsules; 3f) Low-temperature drying: The water-containing antibacterial microcapsules obtained in step 3e) are placed in a low-temperature drying environment of 40-60℃ and dried for 2-4 hours to obtain dried antibacterial microcapsules with a particle size of 1-5μm.

6. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (4), the mass fraction of the dilute acid solution is 1-2%, the concentration of the chitosan solution is 1-3wt%, the pH of the neutral buffer solution is 7.0-7.4, the concentration of the silk fibroin solution is 2-4wt%, the amount of crosslinking agent added is 0.5-1.5% of the total mass of the mixed solution, and the vacuum degassing time is 10-20 min; In step (4), the dilute acid solution is dilute acetic acid or dilute hydrochloric acid, and the crosslinking agent is one of glutaraldehyde and genipin.

7. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (5), the concentration of the porous scaffold precursor solution is 5-10 wt%, the amount of antibacterial microcapsules added is 8-15% of the total mass of the porous scaffold precursor solution, the high-speed dispersion rate is 600-800 r / min, the dispersion time is 20-30 min, the mass ratio of pore-forming agent to polymer substrate is 1:2-1:4, the stirring time for adjusting pore structure is 10-15 min, and the vacuum degassing time is 10-20 min.

8. The method for preparing the antibacterial dressing according to claim 7, characterized in that, In step (5), the biocompatible polymer substrate is at least one of polycaprolactone, polyethylene glycol, and hyaluronic acid; the solvent is one or a mixture of two of deionized water and ethanol; and the pore-forming agent is one of sodium chloride and mannitol.

9. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (6), the coating thickness of the surface film-forming liquid is 0.1-0.3 mm, the drying temperature is 40-50℃, and the drying time is 2-4 h; In step (6), the thickness of the intermediate layer precursor liquid coating is 0.3-0.8 mm, the freezing rate is 5-10℃ / h, the temperature is lowered to -40~-60℃ and then kept at the temperature for 2-4 h, and the freeze drying conditions are -40~-60℃, vacuum degree is 10-30 Pa, and drying time is 18-24 h. In step (6), the thickness of the high-permeability bottom layer is 0.2-0.4 mm, and the composite method is hot-press composite or interface cross-linking composite. The hot-press composite temperature is 60-80℃, the pressure is 0.1-0.3MPa, and the time is 10-20 min. In step (6), the highly breathable bottom layer is a polytetrafluoroethylene porous membrane or non-woven fabric with a porosity of 60-80% and a water vapor permeability of 2000-3000 g / (m²). 2 •24h).

10. The method for preparing the antibacterial dressing according to claim 2, characterized in that, In step (7), the number of times of washing with deionized water is 2-3 times, the washing time for each time is 10-15 min, the crosslinking curing temperature is 50-60℃, and the curing time is 6-12 h; In step (7), the sterilization method is irradiation sterilization, and the irradiation dose is 20-30 kGy.

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