Preparation and application of bismuth-containing composite nanofiber

Abstract

This invention provides a bismuth-containing composite fiber, its preparation method, and its applications. Specifically, this invention provides a bismuth-containing composite fiber, which is a polymer electrospun fiber with bismuth-bismuth oxide particles doped on its surface and / or internally. The polymer comprises a first polymer and a second polymer. The blending of the two polymers not only imparts excellent mechanical strength to the composite fiber but also ensures its biodegradability and biocompatibility. The introduction of bismuth-bismuth oxide particles endows the nanofiber with functional properties, enabling it to generate reactive oxygen species under ultrasound, achieving highly efficient antibacterial effects and thus meeting the customized functional requirements for antibacterial treatment on wound surfaces. The bismuth-containing composite fiber prepared by this invention has advantages such as good biocompatibility, excellent antibacterial effect, high mechanical strength, and low bioirritation, showing promising application prospects in biomedical fields such as wound dressings.

Description

Technical Field

[0001] This invention relates to the field of biofunctional materials technology, and in particular to a bismuth-containing composite nanofiber, its preparation method and application. Background Technology

[0002] Electrospinning, as an advanced and efficient processing method for preparing continuous nanofibers, has shown broad application prospects in the biomedical field, particularly in antibacterial materials research, in recent years. This technology uses a high-voltage electrostatic field to charge a polymer solution or melt, which is then sprayed and stretched, ultimately solidifying to form a fiber structure with diameters ranging from tens to hundreds of nanometers. This ultrafine fiber structure can mimic the topological morphology of the natural extracellular matrix, providing an ideal microenvironment for cell growth. Simultaneously, its large specific surface area and highly interconnected porous network structure significantly enhance the material's adsorption capacity, permeability, and functional loading potential, making it an ideal platform for constructing next-generation functional biomedical materials.

[0003] Among polymer materials suitable for electrospinning, polyvinyl alcohol (PVA) has attracted considerable attention due to its excellent biocompatibility and water solubility. The PVA molecular chain is rich in hydroxyl groups, possessing excellent hydrophilic properties and controllable degradation performance. Based on these properties, its nanofibers have unique advantages in fields such as absorbable wound dressings, drug-controlled release carriers, and tissue engineering scaffolds. Particularly in wound care, PVA nanofiber membranes can effectively absorb tissue exudate while maintaining a suitable moist environment on the wound. This aligns closely with modern moist wound healing theory, accelerating epithelial cell migration and granulation tissue formation, and significantly promoting wound healing. However, PVA nanofibers have significant drawbacks: poor mechanical properties, manifested as insufficient tensile strength, limited elongation at break, and poor durability. They are particularly prone to swelling, deformation, and even disintegration in moist environments, severely limiting their application in applications subject to mechanical loads.

[0004] In contrast, polylactic acid (PLA), a synthetic polyester derived from renewable resources, not only possesses complete biodegradability but also exhibits mechanical properties far superior to polyvinyl alcohol (PVA). PLA nanofibers possess high tensile strength and modulus, and its degradation product, lactic acid, can participate in in vivo metabolic cycles, with its biocompatibility widely verified. However, PLA materials are inherently hydrophobic, which is detrimental to cell adhesion and growth, and the degradation process may induce localized acidic environments, limiting its application in the repair of certain sensitive tissues. Although PVA and PLA exhibit significant complementary properties, simple physical blending or bilayer composites often fail to achieve synergistic performance enhancement. Particularly in the antibacterial field, neither polymer possesses inherent antibacterial activity; without functional modification, their composite system cannot meet the requirements for highly efficient and sustained inhibition of specific pathogenic microorganisms, making customized antibacterial performance design difficult.

[0005] Therefore, there is a need in the field for a composite nanofiber that has antibacterial properties and effectively promotes wound healing. Summary of the Invention

[0006] The purpose of this invention is to provide a method for preparing bismuth-containing composite nanofiber materials and their applications.

[0007] In a first aspect of the present invention, a bismuth-containing composite fiber material is provided, the bismuth-containing composite fiber material being a polymer electrospun fiber, the surface and / or interior of which are doped with bismuth-bismuth oxide particles, wherein the polymer comprises a first polymer and a second polymer, wherein the first polymer and the second polymer are each independently selected from the group consisting of: polyvinyl alcohol, polylactic acid, polyvinylpyrrolidone, polyethylene glycol, polyacrylamide, polyvinyl acetate, polyglycolic acid, polybutylene succinate, and polycaprolactone, provided that the first polymer and the second polymer are not the same.

[0008] In another preferred embodiment, the diameter of the bismuth-containing composite fiber material is 0.1-50 μm, preferably 0.5-2 μm.

[0009] In another preferred embodiment, the bismuth-containing composite fiber material generates active oxygen under ultrasonic treatment.

[0010] In another preferred embodiment, the power of the ultrasound is 0.5-3 W / cm². 2 Preferably 1-2 W / cm 2 .

[0011] In another preferred embodiment, the duration of the ultrasound is 1-10 min, preferably 1-5 min.

[0012] In another preferred embodiment, the molar ratio of bismuth to bismuth oxide in the bismuth-bismuth oxide particles is 1:(0.5-2), preferably 1:(1-1.5), for example 1:1.35.

[0013] In another preferred embodiment, the bismuth-bismuth oxide particles have a particle size of 40-100 nm, preferably 50-80 nm, and more preferably 50-60 nm.

[0014] In another preferred embodiment, the first polymer is selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, polyacrylamide, and polyvinyl acetate, preferably polyvinyl alcohol; the second polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polybutylene succinate, and polycaprolactone, preferably polylactic acid.

[0015] In another preferred embodiment, based on the total mass of the composite fiber material, the content of the bismuth-bismuth oxide particles is 1-20%, preferably 1-10%, more preferably 1-5%; the content of the first polymer is 1-95%, preferably 5-90%, more preferably 10-85%, more preferably 20-70%, more preferably 30-60%, more preferably 40-55%; and the content of the second polymer is 1-95%, preferably 5-90%, more preferably 10-85%, more preferably 20-70%, more preferably 30-60%, more preferably 40-55%.

[0016] In another preferred embodiment, the molecular weight of the first polymer is 80,000 to 120,000, preferably 90,000 to 110,000.

[0017] In another preferred embodiment, the molecular weight of the second polymer is 80,000 to 120,000, preferably 90,000 to 110,000.

[0018] In another preferred embodiment, the method for preparing the bismuth-containing composite fiber material includes the following steps: N1, providing a solution containing a first polymer and a second polymer, and bismuth-bismuth oxide particles; N2. Mix the solution from step N1 with bismuth-bismuth oxide particles to form a spinning solution; N2. Electrospinning is performed on the spinning solution to prepare bismuth-containing composite fiber material.

[0019] In another preferred embodiment, the preparation method is as described in the second aspect of the present invention.

[0020] In another preferred embodiment, the bismuth-containing composite fiber material has one or more features selected from the group consisting of: (1) The maximum load of the bismuth-containing composite fiber material is 4-10 MPa, preferably 5-8 MPa, for example 6 MPa; (2) The rigidity and toughness of the bismuth-containing composite fiber material are more than twice that of single polymer spun fibers; (3) The water contact angle of the bismuth-containing composite fiber material is 0°~50°, preferably 10°~40°, and more preferably 20°~30°.

[0021] In another preferred embodiment, the bismuth-containing composite fiber material, combined with ultrasonic treatment, has one or more features selected from the group consisting of: A. Improves wound healing speed, wherein the wound heals in 10-13 days; B. Accelerates tissue regeneration and remodeling, wherein the new epithelium and skin appendages are formed in 6-8 days, and the wound skin structure recovers to its normal physiological state in 10-13 days; C. Reduce the degree of inflammatory infiltration.

[0022] In a second aspect, the present invention provides a method for preparing a bismuth-containing composite fiber material as described in the first aspect, comprising the following steps: N1, providing a solution containing a first polymer and a second polymer, and bismuth-bismuth oxide particles; N2. Mix the solution from step N1 with bismuth-bismuth oxide particles to form a spinning solution; N2. Electrospinning is performed on the spinning solution to prepare bismuth-containing composite fiber material.

[0023] In another preferred embodiment, in step N1, the mass ratio of the first polymer to the second polymer is 1:0.5 to 1:5.

[0024] In another preferred embodiment, in step N1, a solution comprising the first polymer and the second polymer is formed using a solvent selected from the group consisting of water, hexafluoroisopropanol, trifluoroethanol, hexafluoroacetone hydrate, dimethylformamide, or combinations thereof, preferably a mixture of water and hexafluoroisopropanol.

[0025] In another preferred embodiment, in step N1, when the solvent is a mixture of water and hexafluoroisopropanol, the mass ratio of water to hexafluoroisopropanol is 1:(0.5-1:5).

[0026] In another preferred embodiment, step N1 further includes the step: N1-1, adding the first and second polymers to the solvent, and stirring for 1 to 5 h in a water bath at 20 to 80 °C and at 200 to 1500 rpm to prepare the solution containing the first polymer and the second polymer.

[0027] In another preferred embodiment, based on the total mass of the spinning solution formed in step N2, the mass concentration of the first polymer and the second polymer in the spinning solution is 5-20%, and the mass concentration of bismuth-bismuth oxide particles is 0.1-5%. In another preferred embodiment, step N2 further includes the step: N2-1, mixing the solution from step N1 with bismuth-bismuth oxide particles and stirring at 200-1500 rpm for 1-12 h to prepare a spinning solution.

[0028] In another preferred embodiment, in step N3, the electrospinning process parameters are: micro-nozzle model 10G-30G, electrospinning flow rate 0.5-5 mL / h, spinning voltage 10-30 kV, spinning ambient temperature 20-30 ℃, and spinning ambient relative humidity 50-70%.

[0029] In another preferred embodiment, the method for preparing the bismuth-bismuth oxide particles includes the following steps: S1. Provide bismuth-containing compounds and reducing agents; S2. Mix the bismuth-containing compound and the reducing agent, heat under an inert atmosphere to carry out the reaction, and wash with an alcoholic solution of the dispersant to prepare bismuth-bismuth oxide particles.

[0030] In another preferred embodiment, the bismuth-containing compound is selected from the group consisting of bismuth nitrate, bismuth chloride, bismuth acetate, triphenylbismuth, and bismuth methanesulfonate, preferably bismuth nitrate.

[0031] In another preferred embodiment, the reducing agent is selected from the group consisting of: dodecyl mercaptan, sodium borohydride, sodium hydride, and ascorbic acid, preferably dodecyl mercaptan.

[0032] In another preferred embodiment, the molar ratio of the bismuth-containing compound to the reducing agent is 1:9 to 1:40.

[0033] In another preferred embodiment, the dispersant is selected from the group consisting of: povidone K30, povidone K90, polyethylene glycol 400, polyethylene glycol 2000, and polyethylene glycol 4000.

[0034] In another preferred embodiment, the alcohol solution is C 1-5 An alcoholic solution, preferably an ethanol solution.

[0035] In another preferred embodiment, the dispersant has a mass concentration of 5-50% in the alcohol solution.

[0036] In another preferred embodiment, the heating reaction temperature is 120-180 °C.

[0037] In another preferred embodiment, the reaction time is 10 min to 2 h.

[0038] In a third aspect, the present invention provides a medical material comprising a bismuth-containing composite fiber material as described in the first aspect of the present invention and pharmaceutically acceptable excipients.

[0039] In another preferred embodiment, the pharmaceutically acceptable excipient is selected from the group consisting of: plasticizers, humectants, stabilizers, antioxidants, crosslinking agents, binders, buffers, osmotic pressure regulators, surfactants, biodegradable additives, fillers, pore-forming agents, or combinations thereof.

[0040] In another preferred embodiment, the medical material is a topical medical material.

[0041] In a fourth aspect, the present invention provides the use of a bismuth-containing composite fiber material as described in the first aspect of the present invention or a medical material as described in the third aspect of the present invention for preparing a wound dressing for antibacterial purposes.

[0042] In another preferred embodiment, the wound dressing is used for hemostasis, physical isolation, chronic wound care, promoting wound healing, or a combination thereof.

[0043] In another preferred embodiment, promoting wound healing means promoting wound tissue regeneration, promoting wound closure, and promoting the regeneration of normal physiological tissues.

[0044] In another preferred embodiment, promoting wound healing refers to removing wound exudate, providing antioxidant protection to the wound, isolating the wound, keeping the wound dry, and preventing infection, or a combination thereof.

[0045] In another preferred embodiment, the chronic wound care refers to descaling wound exudate, wound anti-oxidation, wound isolation, keeping wound dry, anti-infection, or a combination thereof.

[0046] In another preferred embodiment, the anti-infection refers to reducing and / or eliminating pathogenic bacterial infection at the wound site.

[0047] In another preferred embodiment, the pathogen causing the infection is a Gram-positive bacterium, a Gram-negative bacterium, a fungus, or a combination thereof; more preferably, the pathogen is selected from the group consisting of aerobic bacteria, anaerobic bacteria, or a combination thereof; even more preferably, the pathogen is selected from the group consisting of Staphylococcus aureus, vancomycin-resistant enterococci, hemolytic streptococci, Staphylococcus epidermidis, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Cryptococcus neoformans, Candida albicans, Candida glabrata, or a combination thereof.

[0048] In a fifth aspect, the present invention provides a method for inhibiting bacteria, comprising the steps of: L1. After bacteria come into contact with the bismuth-containing composite fiber material described in the first aspect of the present invention, they are subjected to ultrasonic treatment, which reduces the growth and reproduction of bacteria. The bacteria are Gram-positive bacteria, Gram-negative bacteria, fungi, or combinations thereof.

[0049] In another preferred embodiment, the bacteria are selected from the group consisting of aerobic bacteria, anaerobic bacteria, or combinations thereof; more preferably, the bacteria are selected from the group consisting of Staphylococcus aureus, vancomycin-resistant enterococci, hemolytic streptococci, Staphylococcus epidermidis, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Cryptococcus neoformans, Candida albicans, Candida glabrata, or combinations thereof.

[0050] In another preferred embodiment, the contact refers to inoculating a bacterial suspension containing bacteria onto a bismuth-containing composite fiber material.

[0051] In another preferred embodiment, the method is in vitro.

[0052] In another preferred embodiment, the method is non-diagnostic and non-therapeutic.

[0053] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0054] Figure 1 The X-ray powder diffraction pattern of bismuth-bismuth oxide (Bi@Bi2O3) and the X-ray photoelectron spectrum of bismuth are provided for this invention.

[0055] Figure 2 Transmission electron microscope (TEM) images of bismuth-bismuth oxide (Bi@Bi2O3) and bismuth-containing composite nanofibers provided for this invention.

[0056] Figure 3 Scanning electron microscope (SEM) image of bismuth-containing nanocomposite fibers provided for this invention.

[0057] Figure 4 Stress-strain curves of polyvinyl alcohol, polylactic acid, polylactic acid and polyvinyl alcohol composites (1:1), and bismuth-bismuth oxide nanoparticles and polylactic acid-polyvinyl alcohol composites (1:1) provided by the present invention.

[0058] Figure 5 Degradation curves of bismuth-bismuth oxide (Bi@Bi2O3) and reference bismuth (Bi) with ROS probe (1,3-diphenylisobenzofuran, DPBF) provided for this invention.

[0059] Figure 6 Electron paramagnetic resonance (ESR) spectra of bismuth-containing nanocomposite fibers provided by the present invention under ultrasonic conditions.

[0060] Figure 7 The water contact angle test diagrams of the bismuth-containing nanocomposite fibers provided by the present invention at 0, 3, 5, and 10 seconds are shown.

[0061] Figure 8 The graph shows the in vitro antibacterial performance test results of different groups provided by this invention.

[0062] Figure 9 The image shows the changes in the appearance of rat wound healing over time in different treatment groups provided by this invention.

[0063] Figure 10 The figure shows the statistical results of the wound area of ​​rats in different groups provided by this invention.

[0064] Figure 11 This is a hematoxylin-eosin (H&E) staining image of wound sections from different groups in this invention. Detailed Implementation

[0065] Through extensive and in-depth research, the inventors have discovered for the first time a bismuth-containing composite fiber material. This invention utilizes electrospinning technology to combine bismuth-bismuth oxide (Bi@Bi2O3) nanoparticles with two polymers. Upon ultrasonic stimulation, the nanoparticles generate active oxygen, thereby imparting antibacterial properties while maintaining the mechanical properties of the nanofibers, achieving highly efficient antibacterial activity and promoting wound healing. This invention is based on this discovery.

[0066] the term Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0067] As used herein, the terms “comprising,” “including,” and “containing” are used interchangeably and include not only closed definitions but also semi-closed and open definitions. In other words, the terms include “consisting of” and “substantially consisting of”.

[0068] In this invention, unless otherwise stated, all proportions are by weight, all percentages are by weight, temperature is measured in °C, and pressure is measured in Pascals. Room temperature refers to the normal ambient temperature in a laboratory, which varies with season and location, and is typically 25 °C. Furthermore, all numerical ranges described in this invention include extreme values ​​and may include new numerical ranges obtained by arbitrarily combining the upper and lower limits of the disclosed ranges. For example, if the weight percentage of a certain component is disclosed as 10-30% by weight, preferably 15-25% by weight, more preferably 20-23% by weight, it is equivalent to simultaneously disclosing the following numerical ranges: 10-15% by weight, 10-25% by weight, 10-20% by weight, 10-23% by weight, 15-30% by weight, 15-20% by weight, 15-23% by weight, 20-25% by weight, and 23-25% by weight.

[0069] Bismuth-bismuth oxide particles Inorganic nanomaterials can endow nanofibers with antibacterial effects. Among numerous candidate materials, bismuth (Bi) nanoparticles have emerged due to their unique physicochemical properties and biological effects. Compared with traditional antibacterial metals such as silver and copper, bismuth exhibits significantly lower cumulative toxicity in the human body and demonstrates better biocompatibility with mammalian cells. In electrospun composite systems, bismuth nanoparticles can be stably loaded onto the interior or surface of nanofibers through blend spinning or finishing techniques, which not only significantly increases the specific surface area of ​​the material but also introduces significant quantum size and surface effects.

[0070] Bismuth nanoparticles exhibit external stimulus-responsive properties. Under external field excitation such as ultrasound, they can promote electron-hole pair separation through changes in band structure, catalyzing the generation of bactericidal substances such as reactive oxygen species (ROS), thus achieving a sonodynamic antibacterial effect. This property provides a new approach for developing external stimulus-responsive smart antibacterial materials.

[0071] This invention uses bismuth-bismuth oxide as a therapeutic active component, which is incorporated into the spinning solution, and a dressing containing bismuth-bismuth oxide active ingredient is prepared by spinning process.

[0072] dressing The dressing of the present invention is in the form of a fabric composed of composite fibers. In this invention, the dressing can be regarded as a carrier or scaffold for the active component deferoxamine. Therefore, in the following description, the terms "dressing," "fabric," "scaffold," and "carrier" are used interchangeably to refer to the dressing described in this invention. Additionally, the terms "fiber" and "spinning" are used interchangeably. In the following examples, polyvinyl alcohol and chitosan are used as specific examples of the synthetic and natural polymers, but other synthetic and natural polymers with similar properties may also be used.

[0073] The dressing of the present invention is prepared by a spinning process. Specifically, the first polymer and the second polymer selected in this invention are each prepared into solutions in water or other suitable solvents, and then these two solutions are mixed with bismuth-bismuth oxide particles to form a raw material solution for the spinning process.

[0074] When preparing the polymer solution, other additives may be added to the solution as needed. Examples of such additives include one or more of the following: pH adjusters, stabilizers, dispersants, and thickeners.

[0075] According to one embodiment of the present invention, the raw material solution used in the spinning process does not contain any other components besides the above-mentioned bismuth-bismuth oxide, first polymer and second polymer.

[0076] The bismuth-bismuth oxide can be mixed as a separate component with the solutions of the first polymer and the second polymer. According to another embodiment of the invention, bismuth-bismuth oxide can be first added to either the solution of the first polymer or the solution of the second polymer, and then the resulting solution can be mixed with another polymer solution.

[0077] Bismuth-containing composite fiber materials This invention provides a bismuth-containing nanocomposite fiber material, a method for preparing the material, and its application in the field of antibacterial applications.

[0078] The bismuth-containing nanocomposite fiber material comprises composite nanofibers formed from bismuth-bismuth oxide (Bi@Bi2O3) nanoparticles, polyvinyl alcohol (PVA), and polylactic acid (PLA).

[0079] This material uses bismuth-bismuth oxide nanoparticles as the functional component and a blend of polyvinyl alcohol and polylactic acid as the matrix. It is formed into composite nanofibers with excellent mechanical properties and stimulus-responsive antibacterial properties through electrospinning process, which solves the technical problems of insufficient antibacterial activity and difficulty in synergistic optimization of mechanical properties and biocompatibility of existing polymer nanofibers.

[0080] This invention also provides the application of bismuth-containing nanocomposite fiber materials generating active oxygen under ultrasonic treatment for antibacterial purposes.

[0081] This invention also provides the application of bismuth-containing nanocomposite fiber materials as wound dressings for antibacterial and wound healing promotion.

[0082] This invention also provides the application of bismuth-containing nanocomposite fiber materials in the preparation of antibacterial wound dressings.

[0083] Preparation method The raw materials for preparation include the following components: bismuth nitrate pentahydrate, dodecyl mercaptan, polyvinyl ketone K30, ethanol, polyvinyl alcohol, polylactic acid, and hexafluoroisopropanol; the preparation method includes the following steps: Step 1: Mix bismuth nitrate pentahydrate and dodecyl mercaptan evenly in a three-necked flask, circulate the gas three times to remove air from the system, slowly heat and keep warm under nitrogen protection for a period of time, and then cool to room temperature; collect the black precipitate by centrifugation (1000~15000 rpm, 1~20 min), wash several times with ethanol containing povidone K30, disperse the collected product in ethanol, and store at 4 ℃. Step 2: Mix water and hexafluoroisopropanol, then add polyvinyl alcohol and polylactic acid, and stir for 1-5 h in a water bath at 20-80 ℃ and 200-1500 rpm; add bismuth-bismuth oxide nanoparticles, and stir at 200-1500 rpm for 1-12 h at room temperature; transfer the spinning solution into an electrospinning machine, set the spinning parameters, and perform electrospinning to obtain bismuth-containing nanocomposite fibers.

[0084] Preferably, the preparation method satisfies at least one of the following conditions: Condition 1: The mass concentration of bismuth nitrate in dodecanethiol in step 1 is 5-20%; Condition 2: The reaction temperature in step 1 is 120~180 ℃; Condition 3: The reaction time in step 1 is 10 min to 2 h; Condition 4: The mass concentration of povidone K30 in ethanol in step 1 is 5-50%; Condition 5: The mass ratio of water to hexafluoroisopropanol in step 2 is 1:0.5 to 1:5; Condition 6: In step 2, the mass ratio of polylactic acid (molecular weight 1~220,000) to polyvinyl alcohol (molecular weight 1~150,000) is 1:0.5~1:5, and the mass concentration is 5~20%; Condition 7: The mass concentration of bismuth-bismuth oxide in step 2 is 0.1~5%.

[0085] Condition 8: The electrospinning process parameters in step 2 are as follows: micro-nozzle model 10G~30G, electrospinning flow rate 0.5~5 mL / h, spinning voltage 10~30 kV, spinning ambient temperature 20~30 ℃, and spinning ambient relative humidity 50~70%.

[0086] The main advantages of this invention include: (1) The bismuth-containing composite fiber material provided by the present invention can generate active oxygen under ultrasonic action to achieve a highly efficient antibacterial effect.

[0087] (2) The bismuth-containing composite fiber material provided by the present invention has excellent rigidity and toughness, and its mechanical strength is significantly improved.

[0088] (3) The bismuth-containing composite fiber material provided by the present invention has a strong affinity for water molecules, good biocompatibility and low biostimulation.

[0089] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight.

[0090] Example 1. Synthesis of bismuth-bismuth oxide nanoparticles 500 mg Bi(NO3)3•5H2O and 5 mL dodecanethiol were mixed thoroughly in a three-necked flask, and the mixture was evacuated three times to remove excess air. The mixture was then slowly heated to 150 °C under nitrogen protection and held at this temperature for 30 min, followed by cooling to room temperature. The black precipitate was collected by centrifugation (13500 rpm, 10 min), washed several times with an ethanol solution containing 5% povidone K30, and the collected product was dispersed in ethanol and stored at 4 °C.

[0091] Example 2. Synthesis of bismuth-bismuth oxide nanoparticles 250 mg Bi(NO3)3•5H2O was mixed thoroughly with 5 mL of dodecanethiol in a three-necked flask, and the mixture was evacuated three times to remove excess air. The mixture was then slowly heated to 150 °C under nitrogen protection and held at this temperature for 30 min, followed by cooling to room temperature. The black precipitate was collected by centrifugation (13500 rpm, 10 min), washed several times with an ethanol solution containing 5% povidone K30, and the collected product was dispersed in ethanol and stored at 4 °C.

[0092] Example 3. Synthesis of bismuth-bismuth oxide nanoparticles 750 mg Bi(NO3)3•5H2O was mixed thoroughly with 5 mL of dodecanethiol in a three-necked flask, and the mixture was evacuated three times to remove excess air. The mixture was then slowly heated to 150 °C under nitrogen protection and held at this temperature for 30 min, followed by cooling to room temperature. The black precipitate was collected by centrifugation (13500 rpm, 10 min), washed several times with ethanol containing 5% povidone K30, and the collected product was dispersed in ethanol and stored at 4 °C.

[0093] To determine the ratio of bismuth to bismuth oxide in the prepared nanoparticles, the inventors conducted the following characterization experiments: Figure 1 The image shown is an X-ray powder diffraction (XRD) image of bismuth-bismuth oxide nanoparticles. The structure of the bismuth-bismuth oxide nanoparticles in Synthesis Example 1 was analyzed by crystal structure determination. The ratio of bismuth to bismuth oxide was found to be 1:1.35. Furthermore, X-ray electron spectroscopy (XPS) results showed that bismuth has both 0 and +3 valences, consistent with the X-ray diffraction results, thus confirming the structure and composition of the bismuth-bismuth oxide nanoparticles.

[0094] Example 4. Preparation and performance characterization of composite nanofibers (1) Preparation of composite nanofibers: 5 mL of water and 5 mL of hexafluoroisopropanol were mixed, followed by the addition of 500 mg of polyvinyl alcohol (molecular weight: 100,000) and 500 mg of polylactic acid (molecular weight: 100,000). The mixture was stirred at 800 rpm for 2 h in a 60 ℃ water bath. Then, 20 mg of bismuth-bismuth oxide nanoparticles were added, and the mixture was stirred at 1000 rpm for 6 h at room temperature. After the spinning solution was prepared, it was transferred to an electrospinning machine with the following spinning parameters set: voltage 19 kV, receiving distance 13-15 cm, roller speed 500 rpm, flow rate 15 μL / min, and 22G needles used. Bismuth-containing nanocomposite fibers were obtained through electrospinning.

[0095] (2) Morphology characterization of composite nanofibers: To verify the synthesis effect of nanomaterials and the microstructure of composite fibers, the following characterization experiments were conducted: Figure 2 Transmission electron microscopy (TEM) images of bismuth-bismuth oxide nanoparticles and bismuth-containing composite nanofibers are presented, showing that bismuth-bismuth oxide nanoparticles can be effectively composited into the nanofiber matrix; furthermore... Figure 3 Scanning electron microscope (SEM) images showed that the prepared bismuth-containing composite nanofibers had a uniform diameter distribution and no obvious agglomeration.

[0096] (3) Evaluation of the mechanical properties of composite nanofibers: To verify the mechanical strength of this biological scaffold material, a mechanical strength test was conducted. The stress-strain of the prepared nanofiber membrane was evaluated using a Z2.5TH electronic universal testing machine. After cleaning the test sample, it was cut into strips of 3×5 cm, and the stress-strain relationship of the material was measured after applying a preload.

[0097] The result is as follows Figure 4 As shown, the prepared polyvinyl alcohol / polylactic acid (PVA / PLA) exhibits superior elastic properties and a higher yield plateau compared to single polymer materials. The maximum load of the spun film from a single polymer is 2 MPa, while the maximum load of the blended textile can be increased to 6 MPa, demonstrating excellent overall rigidity and toughness. Furthermore, the loading of bismuth-bismuth oxide nanoparticles does not affect the overall mechanical properties, which still exhibit relatively excellent mechanical properties.

[0098] (4) Release of reactive oxygen species from composite nanofibers under ultrasonic treatment: To verify the ROS generation capability of the prepared electrospun film, the inventors conducted a ROS capture experiment. At 1 W / cm² 2 And under ultrasonic treatment for 3 minutes, the inventors used DPBF as a trapping agent and compared the degradation curves of bismuth-bismuth oxide nanoparticles and elemental bismuth under ultrasonic treatment, indicating that the generation of ROS originated from bismuth-bismuth oxide nanoparticles ( Figure 5 Under the same conditions, the ESR results further clarified that the ROS generated by the electrospun film were singlet oxygen (scavenger: 2,2,6,6-tetramethylpiperidinoxy, TEMP) and hydroxyl radicals (scavenger: 5,5-dimethyl-1-pyrrolidone N-oxide, DMPO). Figure 6 ).

[0099] Both results indicate that Bi@Bi2O3 nanoparticles produce the most ROS. Therefore, the formation of a Bi@Bi2O3 composite structure is a necessary condition for increased ROS production.

[0100] (5) Evaluation of the hydrophilicity of composite nanofibers The surface wetting properties of nanofiber films were characterized using a contact angle measurement instrument, and the tests were conducted at room temperature and atmospheric pressure. A quantitative amount of deionized water was taken using a micro-syringe and vertically dropped onto the flat surface of the nanofiber film under test. The dynamic wetting behavior of the droplets was recorded in real time using the instrument's imaging system. The droplet morphology was collected at four time points: 0 s, 3 s, 5 s, and 10 s, and the hydrophilic properties of the film were analyzed accordingly.

[0101] The test results show that ( Figure 7 The fact that water droplets can spread fully within 10 seconds proves that composite nanofibers have a strong affinity for water molecules.

[0102] Example 5. In vitro antibacterial performance test of composite nanofibers Take a concentration of 1×10 7 A bacterial suspension of CFU / mL was prepared by first placing 25 mg of Bi@Bi2O3 / PVA / PLA composite nanofiber membrane in a 50 mL sterile test tube and sterilizing it by irradiation with a UV lamp for 30 min. Then, 5 mL of the bacterial suspension was inoculated onto the sterilized composite nanofiber membrane surface using a micropipette and sonicated for 2 min. After sonication, bacteria on the sample surface were eluted with 20 mL of 0.01 M, pH 7.4 PBS buffer, and the eluent was thoroughly mixed. Finally, a portion of the eluent was serially diluted 100-fold, and 100 μL of the diluted eluent was evenly spread onto the surface of nutrient agar medium and incubated at 37 ℃ for 24 h. The in vitro antibacterial effect of the sample was evaluated by counting the number of colonies.

[0103] The test results show that ( Figure 8 The plate colony test results showed that ultrasonic treatment alone and nanofiber materials alone only exhibited weak antibacterial effects against Staphylococcus aureus and Escherichia coli, and could not effectively inhibit the proliferation of pathogenic bacteria. The combined treatment group of nanofibers and ultrasound showed a very strong synergistic antibacterial effect, significantly reducing the number of Staphylococcus aureus colonies and achieving near-complete growth inhibition of Escherichia coli, demonstrating excellent broad-spectrum antibacterial properties.

[0104] Example 6. In vivo antibacterial and wound healing promoting effects test The experiment used rats as a model animal, and the specific procedures were as follows: Rats were first anesthetized intraperitoneally. After anesthesia, the skin on the back of each rat was shaved using a special shaver. A 10 mm diameter skin biopsy sampler was used to mark the skin on the rat's back. Then, the marked area of ​​skin was excised using sterile surgical scissors to construct a 10 mm diameter full-thickness skin wound model on the rat's back. 50 μL of a 1×10⁻⁶ concentration was used... 5A rat model of infection was established by dripping CFU / mL Staphylococcus aureus bacterial suspension onto the wound and spreading it evenly. Two hours after inoculation, each wound was covered with the corresponding dressing, wrapped with sterile gauze, and secured with an elastic bandage. Twenty-four hours after inoculation, the fluid accumulated at the rat wound site was collected, smeared onto a solid culture medium, and incubated at 37°C for 24 hours to confirm the successful establishment of the infection model.

[0105] Rats with successfully established infection models were randomly divided into 5 groups (n = 5 per group). The treatment protocols for each group were as follows: Group 1 (negative control group): uninfected wounds, allowed to heal naturally; Group 2 (positive control group): infected wounds, allowed to heal naturally; Group 3 (pure material group): infected wounds covered with Bi@Bi2O3 / PVA / PLA composite nanofiber membranes; Group 4 (pure US group): infected wounds treated with a 1 W / cm² hydrochloric acid membrane. 2 The treatment involved two groups: Group 1 (material + ultrasound combined treatment group) and Group 2 (bacterial wound). The infected wound was covered with a Bi@Bi2O3 / PVA / PLA composite nanofiber membrane and then treated with the above ultrasound parameters for 2 minutes. All dressings were sterilized by ultraviolet irradiation for 30 minutes and pre-swelled with physiological saline for 10 minutes before use. Wound dressings were changed every two days, and changes in wound area and body weight were recorded daily during the experiment.

[0106] Experimental results show that ( Figures 9-11 The initial wound areas of mice in each group were basically the same. Over time, the wound areas of all groups showed a decreasing trend to varying degrees. The wound closure rate of the fibrous membrane combined treatment group was the fastest. By day 13, the wound had almost completely healed, and the wound area had almost decreased to zero, demonstrating a significantly better healing effect than the other groups. H&E staining results of the wound tissue showed that nanofiber combined with ultrasound treatment could significantly promote wound re-epithelialization and dermal tissue remodeling. Complete new epithelium and abundant skin appendages could be formed within 7 days, and the wound skin structure had basically returned to a normal physiological state by day 13, with a lower degree of inflammatory infiltration and a significantly better tissue regeneration effect than the other groups.

[0107] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A bismuth-containing composite fiber material, characterized in that, The bismuth-containing composite fiber material is a polymer electrospun fiber, with bismuth-bismuth oxide particles doped on the surface and / or inside. The polymer includes a first polymer and a second polymer, wherein the first polymer and the second polymer are each independently selected from the group consisting of: polyvinyl alcohol, polylactic acid, polyvinylpyrrolidone, polyethylene glycol, polyacrylamide, polyvinyl acetate, polyglycolic acid, polybutylene succinate, and polycaprolactone, provided that the first polymer and the second polymer are different.

2. The bismuth-containing composite fiber material as described in claim 1, characterized in that, The bismuth-containing composite fiber material generates active oxygen under ultrasonic treatment.

3. The bismuth-containing composite fiber material as described in claim 1, characterized in that, The molar ratio of bismuth to bismuth oxide in the bismuth-bismuth oxide particles is 1:(0.5-2), preferably 1:(1-1.5), for example 1:1.

35.

4. The bismuth-containing composite fiber material as described in claim 1, characterized in that, The bismuth-bismuth oxide particles have a particle size of 40-100 nm, preferably 50-80 nm, and more preferably 50-60 nm.

5. The bismuth-containing composite fiber material as described in claim 1, characterized in that, The first polymer is selected from the group consisting of: polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, polyacrylamide, and polyvinyl acetate, preferably polyvinyl alcohol; the second polymer is selected from the group consisting of: polylactic acid, polyglycolic acid, polybutylene succinate, and polycaprolactone, preferably polylactic acid.

6. The bismuth-containing composite fiber material as described in claim 1, characterized in that, Based on the total mass of the composite fiber material, the content of the bismuth-bismuth oxide particles is 1-20%, preferably 1-10%, more preferably 1-5%; the content of the first polymer is 1-95%, preferably 5-90%, more preferably 10-85%, more preferably 20-70%, more preferably 30-60%, more preferably 40-55%; and the content of the second polymer is 1-95%, preferably 5-90%, more preferably 10-85%, more preferably 20-70%, more preferably 30-60%, more preferably 40-55%.

7. The bismuth-containing composite fiber material as described in claim 1, characterized in that, The preparation method of the bismuth-containing composite fiber material includes the following steps: N1, providing a solution containing a first polymer and a second polymer, and bismuth-bismuth oxide particles; N2. Mix the solution from step N1 with bismuth-bismuth oxide particles to form a spinning solution; N2. Electrospinning is performed on the spinning solution to prepare bismuth-containing composite fiber material.

8. A method for preparing a bismuth-containing composite fiber material as described in claim 1, characterized in that, Includes the following steps: N1, providing a solution containing a first polymer and a second polymer, and bismuth-bismuth oxide particles; N2. Mix the solution from step N1 with bismuth-bismuth oxide particles to form a spinning solution; N2. Electrospinning is performed on the spinning solution to prepare bismuth-containing composite fiber material.

9. A medical material comprising the bismuth-containing composite fiber material as described in claim 1 and pharmaceutically acceptable excipients.

10. The use of a bismuth-containing composite fiber material as described in claim 1 or a medical material as described in claim 9, characterized in that, Used to prepare wound dressings for antibacterial purposes.

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