Fiber dressing for promoting wound healing, preparation method and application thereof

Abstract

The present invention provides a fiber dressing that promotes wound healing, as well as its preparation method and application, and belongs to the field of biomaterial technology. The outer shell of the fiber dressing of the present invention contains a first drug that promotes macrophage polarization, which can promote the polarization of macrophages from M1 type to M2 type in normal and diabetic wounds; the outer shell matrix is ​​a mixture of hydrophilic and hydrophobic polymers, which can achieve painless adhesion and peeling of the wound by absorbing exudate and spraying non-irritating saline at the wound surface, thereby reducing secondary damage to the wound surface; the inner core contains a second drug and a third drug that induce the death of M1 macrophages, which can reduce the inflammatory response of the wound surface, kill bacteria on the wound surface, reduce the degree of infection on the wound surface, and accelerate wound healing; the inner core matrix is ​​a mixture of hydrophilic and hydrophobic polymers with good biocompatibility, which can provide mechanical support for the fiber dressing and provide a sustained-release effect for the two substances in the inner core. Controlling the composition of the inner core and the outer shell can effectively promote the healing of normal wounds and diabetic wounds.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomaterials, and in particular relates to a fiber dressing for promoting wound healing, a preparation method and an application thereof. Background Art

[0002] According to the International Diabetes Federation, as of 2021, approximately 537 million adults worldwide are suffering from diabetes. Diabetic wounds are difficult to heal and result in high rates of disability and mortality, significantly harming patients' physical and mental health while also wasting significant medical resources. Long-term infection, secondary damage during dressing changes, and immune disorders at the wound site may hinder rapid healing. Therefore, factors that should be considered in designing ideal dressings include inhibiting bacterial infection, achieving on-demand, controllable adhesion, and regulating the wound's immune response.

[0003] Currently, clinically used dressings for diabetic wound care, such as hydrogels, foams, and semipermeable membranes, often adhere to the wound surface, disrupting newly formed epithelial tissue during dressing changes and causing secondary injury. Furthermore, most of these dressings are immunologically inert and unable to actively participate in immune regulation. Dressing design tailored to healing factors is a research hotspot in biomedical materials. While some basic research on on-demand controllable adhesion or immune regulation is currently underway, the following challenges remain: 1. Research on biomaterials that simultaneously achieve on-demand controllable adhesion and multi-stage immune regulation remains in its infancy; 2. Stimulants in on-demand controllable adhesion dressings developed based on stimuli-responsive strategies diffuse uncontrollably across the wound surface, stimulating the wound microenvironment; and 3. Immunomodulatory dressings based on modified immunoreactive macromolecules or loaded with stem cells, genes, or drugs focus solely on immune regulation at a single stage of healing. Therefore, there is an urgent need to develop antimicrobial dressings that simultaneously achieve non-stimulant on-demand controllable adhesion and multi-stage immune regulation to promote rapid healing of diabetic wounds.

[0004] The prior art patent with the invention publication number CN115350316A discloses a hydrophilic fiber membrane whose inner core includes curcumin and a first spinnable polymer, and whose outer shell includes polyethylene glycol and a second spinnable polymer for achieving the slow release of curcumin. 1. The prior art focuses on the preparation of a hydrophilic fiber membrane that can achieve the sustained release of curcumin. Its membrane can only release curcumin slowly, does not have controllable adhesion, hygroscopic dissolution, multi-stage release of two or more drugs, does not have antibacterial properties, and no cell experiments and animal experiments have been conducted to verify the feasibility of this material as a fiber dressing; the focus of the present invention is to simultaneously achieve non-irritating, on-demand controllable adhesion, multi-stage immune regulation, and anti-wound infection. 2. The external phase of the prior art cannot be dissolved, has only hydrophilic swelling properties, and does not have adhesion; the outer shell of the present invention is a mixture of water-soluble polymers and hydrophobic polymers. When encountering wound secretions, the water-soluble polymer can dissolve to achieve adhesion, and the hydrophobic polymer can avoid the sudden release of polarizing drugs. 3. The prior art can only achieve sustained release of curcumin; however, the shell and core of the present invention contain different drugs, thereby achieving multi-stage release of multiple drugs. Summary of the Invention

[0005] The purpose of the present invention is to provide a fiber dressing with excellent wound healing effects such as non-irritating, on-demand controllable adhesion, multi-stage immune regulation, and resistance to wound infection, as well as a preparation method and application thereof.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a fiber dressing for promoting wound healing, which is composed of micro-nano fibers with a core-shell structure; the outer shell of the fiber comprises a first hydrophilic polymer, a first hydrophobic polymer and a first drug; the inner core of the fiber comprises a second hydrophilic polymer, a second hydrophobic polymer, a second drug and a third drug; the first drug comprises one or more of curcumin, naproxen, paeoniflorin, gallic acid, green tea extract, resveratrol, neurotensin, freeze-dried amniotic membrane-derived conditioned medium and a miR-2235p mimic; the second drug comprises one or more of asiaticoside, quercetin, Fe3O4 nanoparticles, hemin, polyrotaxane containing methylated β-cyclodextrin, sorafenib, cyclosporine and erastin; and the third drug comprises one or more of silver nanoparticles, copper nanoparticles, antibacterial polypeptides and polyionic liquid antibacterial agents.

[0008] Preferably, the mass ratio of the first hydrophilic polymer, the first hydrophobic polymer and the first drug in the shell is (1-10):1:(0.1-0.5).

[0009] Preferably, the mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug and the third drug in the inner core is 1:(1-10):(0.1-0.5):(0.1-0.2).

[0010] Preferably, the first hydrophilic polymer and the second hydrophilic polymer independently include one or more of polyvinyl pyrrolidone, gelatin, sodium alginate, carboxymethyl chitosan, polyvinyl alcohol, polyacrylic acid, recombinant spider silk protein, silk protein, polyethylene glycol, polyethylene oxide, tannic acid adhesive, dextran and pectin.

[0011] Preferably, the first hydrophobic polymer and the second hydrophobic polymer independently include one or more polymers selected from the group consisting of polycaprolactone, polyurethane, polylactic acid, polylactic-co-glycolic acid, cellulose acetate, polydimethylsiloxane, polymethacrylate, polyvinylidene fluoride, polyvinyl acetate, polyester, thermoplastic polyurethane elastomer, ethylene-vinyl acetate polymer, polyamide, polyimide and polylactic-co-glycolic acid, and derivatives thereof.

[0012] The present invention also provides a method for preparing the fiber dressing for promoting wound healing described in the above technical solution, which includes a coaxial electrospinning method, a near-field direct writing method, a microfluidic spinning method or an immersion pulling method.

[0013] The present invention also provides the use of the fiber dressing for promoting wound healing described in the above technical solution or the fiber dressing for promoting wound healing prepared according to the preparation method described in the above technical solution in the preparation of wound dressing.

[0014] The present invention provides a fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure; the outer shell of the fiber comprises a first hydrophilic polymer, a first hydrophobic polymer, and a first drug; the inner core of the fiber comprises a second hydrophilic polymer, a second hydrophobic polymer, a second drug, and a third drug; the first drug comprises one or more of curcumin, naproxen, paeoniflorin, gallic acid, green tea extract, resveratrol, neurotensin, freeze-dried amniotic membrane-derived conditioned medium, and a miR-2235p mimetic; the second drug comprises one or more of asiaticoside, quercetin, Fe3O4 nanoparticles, hemin, polyrotaxane containing methylated β-cyclodextrin, sorafenib, cyclosporine, and erastin; and the third drug comprises one or more of silver nanoparticles, copper nanoparticles, antimicrobial polypeptides, and polyionic liquid antimicrobial agents. The fiber dressing provided by the present invention is composed of coaxial micro-nano fibers. The shell of the coaxial micro-nano fibers contains a first drug that promotes macrophage polarization, which can promote the polarization of macrophages in normal wounds and diabetic wounds from the pro-inflammatory M1 type to the anti-inflammatory M2 type; the shell contains a large amount of hydrophilic polymer, which absorbs exudate at the wound surface, realizes the "dissolution-infiltration-adhesion" effect, and improves the adhesion strength. At the same time, its adhesion strength is mainly affected by the water content of the wound surface. By spraying non-irritating physiological saline, the fiber dressing can be effectively peeled off, reducing secondary damage to the wound surface. Adding a certain amount of The hydrophobic polymer prevents the rapid burst release of the first drug, prolonging its release time. The core contains a second drug that induces the death of M1 macrophages, reducing their number, alleviating inflammatory responses in wounds, and accelerating wound healing. The core also contains a third drug that effectively kills bacteria in wounds and reduces the severity of infection. The core, rich in hydrophobic polymer, retains its intact fiber structure after contact with water during use, providing support and effectively covering the wound, further facilitating wound healing. The addition of a certain amount of hydrophilic polymer allows for an optimal release rate of the second drug. Controlling the composition of the fiber core and shell can effectively promote the healing of both normal and diabetic wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The macroscopic image, microscopic top view and SEM image of a single broken coaxial micro-nanofiber of the fiber dressing in Example 3 are shown;

[0016] Figure 2 The graphs show the cytotoxicity of the control group (PBS), the fiber dressings in Example 3 and Comparative Examples 1 to 4, and 20% dimethyl sulfoxide (DMSO) on human umbilical vein endothelial cells (HUVECs);

[0017] Figure 3The graphs show the cytotoxicity of the control group (PBS), the fiber dressings in Example 3 and Comparative Examples 1 to 4, and 20% dimethyl sulfoxide (DMSO) on human fibroblasts (HDFs);

[0018] Figure 4 This is a graph showing the cytotoxicity of the fiber dressings in Example 3 and Comparative Examples 1 to 4 to mouse macrophages;

[0019] Figure 5 This is a diagram showing the effect of fiber dressings in Example 3 and Comparative Examples 1 to 4 on promoting M1 macrophage polarization;

[0020] Figure 6 The figures are the inhibition zone diameters and quantitative statistical graphs of the fiber dressings in Example 3 and Comparative Examples 1 to 4 against Staphylococcus aureus and Escherichia coli;

[0021] Figure 7 This is a graph showing the change in adhesion strength of the fiber dressing as a function of substrate moisture content in Example 3;

[0022] Figure 8 This is a diagram showing the controlled adhesion experiment of the fiber dressing on the mouse skin wound in Example 3;

[0023] Figure 9 The figures show the healing effects of the fiber dressings in Example 3 and Comparative Examples 1 to 4 on wounds of diabetic mice infected with Staphylococcus aureus and the statistical graphs of the wound healing areas. DETAILED DESCRIPTION

[0024] The present invention provides a fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure; the outer shell of the fiber comprises a first hydrophilic polymer, a first hydrophobic polymer and a first drug; the inner core of the fiber comprises a second hydrophilic polymer, a second hydrophobic polymer, a second drug and a third drug.

[0025] The fiber dressing provided by the present invention comprises micro-nano fibers with a core-shell structure.

[0026] In the present invention, the outer shell of the fiber includes a first hydrophilic polymer, a first hydrophobic polymer and a first drug.

[0027] In the present invention, the first hydrophilic polymer preferably includes one or more of polyvinyl pyrrolidone, gelatin, sodium alginate, carboxymethyl chitosan, polyvinyl alcohol, polyacrylic acid, recombinant spider silk protein, silk protein, polyethylene glycol, polyethylene oxide, tannic acid adhesive, dextran and pectin, more preferably polyvinyl pyrrolidone. In the present invention, the average molecular weight of the polyvinyl pyrrolidone is preferably 300,000 to 400,000 Da, more preferably 360,000 Da. The present invention limits the average molecular weight of polyvinyl pyrrolidone to the above range, which can make the stability of the spinning solution better, and it has suitable solubility, has good adhesion after contact with the wound surface, and is also conducive to subsequent peeling from the wound surface, while allowing the first drug to have a suitable release rate.

[0028] In the present invention, the first hydrophobic polymer preferably includes one or more polymers selected from the group consisting of polycaprolactone, polyurethane, polylactic acid, polylactic acid-co-glycolic acid, cellulose acetate, polydimethylsiloxane, polymethacrylate, polyvinylidene fluoride, polyvinyl acetate, polyester, thermoplastic polyurethane elastomer, ethylene-vinyl acetate polymer, polyamide, polyimide, and polylactic acid-co-glycolic acid, and derivatives thereof, more preferably polycaprolactone. In the present invention, the average molecular weight of the polycaprolactone is preferably 10,000 to 20,000 Da, more preferably 15,000 to 20,000 Da. The present invention limits the average molecular weight of polycaprolactone to the above range, which can improve the stability of the spinning solution, facilitate the preparation of fiber dressings, avoid sudden release of drugs from the shell, and facilitate wound healing.

[0029] In the present invention, the first drug comprises one or more of curcumin, naproxen, paeoniflorin, gallic acid, green tea extract, resveratrol, neurotensin, freeze-dried amniotic membrane-derived conditioned medium, and a miR-2235p mimic, preferably curcumin. In the present invention, the first drug can promote macrophage polarization, promoting the polarization of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type in normal wounds and diabetic wounds. The polarized M2 macrophages can secrete a variety of cytokines and growth factors, promote angiogenesis, collagen deposition, and granulation formation, promote diabetic wounds from the inflammatory phase to the proliferative phase, and accelerate wound healing.

[0030] In the present invention, the mass ratio of the first hydrophilic polymer, the first hydrophobic polymer, and the first drug in the shell is preferably (1-10):1:(0.1-0.5), more preferably (2-10):1:(0.1-0.5), and further preferably (5-10):1:(0.1-0.5). The present invention limits the mass ratio of the first hydrophilic polymer, the first hydrophobic polymer, and the first drug in the shell to the above range. The shell contains a relatively large amount of hydrophilic polymer, which absorbs exudate at the wound surface, realizes the "dissolution-infiltration-adhesion" effect, and improves the adhesion strength. At the same time, its adhesion strength is mainly affected by the water content of the wound surface. By spraying non-irritating physiological saline, the fiber dressing can be effectively peeled off, reducing secondary damage to the wound surface. Adding a certain amount of hydrophobic polymer can avoid the rapid burst release of the first drug and prolong the drug release time.

[0031] In the present invention, the core of the fiber includes a second hydrophilic polymer, a second hydrophobic polymer, a second drug and a third drug.

[0032] In the present invention, the second hydrophilic polymer preferably includes one or more of polyvinyl pyrrolidone, gelatin, sodium alginate, carboxymethyl chitosan, polyvinyl alcohol, polyacrylic acid, recombinant spider silk protein, silk protein, polyethylene glycol, polyethylene oxide, tannic acid adhesive, dextran and pectin, more preferably polyvinyl pyrrolidone. In the present invention, the average molecular weight of the polyvinyl pyrrolidone is preferably 300,000 to 400,000 Da, more preferably 360,000 Da. The present invention limits the average molecular weight of polyvinyl pyrrolidone to the above range, which has suitable solubility, thereby allowing the drug in the core to have a suitable release rate.

[0033] In the present invention, the second hydrophobic polymer preferably includes one or more of the polymers in polycaprolactone, polyurethane, polylactic acid, polylactic acid-co-glycolic acid, cellulose acetate, polydimethylsiloxane, polymethacrylate, polyvinylidene fluoride, polyvinyl acetate, polyester, thermoplastic polyurethane elastomer, ethylene-vinyl acetate polymer, polyamide, polyimide and polylactic acid-co-glycolic acid and their derivatives, more preferably polycaprolactone. In the present invention, the average molecular weight of the polycaprolactone is preferably 10000 to 20000 Da, more preferably 15000 to 20000 Da. The present invention limits the average molecular weight of polycaprolactone to the above range, so that it can maintain the structure of the fiber membrane during use, effectively cover the wound, and be more conducive to wound healing.

[0034] In the present invention, the second drug comprises one or more of asiaticoside, quercetin, Fe3O4 nanoparticles, hemin, a polyrotaxane containing methylated β-cyclodextrin, sorafenib, cyclosporine, and erastin, preferably asiaticoside. In the present invention, the second drug can induce M1 macrophage cell death, reduce the number of M1 macrophages, reduce wound inflammatory response, and accelerate wound healing.

[0035] In the present invention, the third agent preferably comprises one or more of silver nanoparticles, copper nanoparticles, antimicrobial peptides, and polyionic liquid antimicrobial agents, more preferably silver nanoparticles. In the present invention, the third agent can kill Gram-positive bacteria (such as Staphylococcus aureus) and Gram-negative bacteria (such as Escherichia coli) in the wound, reducing the degree of wound infection and promoting wound healing.

[0036] In the present invention, the mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug and the third drug in the inner core is preferably 1: (1-10): (0.1-0.5): (0.1-0.2), more preferably 1: (3-10): (0.1-0.5): (0.1-0.2), and further preferably 1: (5-10): (0.1-0.5): (0.1-0.2). The present invention limits the mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug and the third drug in the inner core to the above range. The inner core contains more hydrophobic polymers, and still has a complete fiber structure after contacting water during use, has a supporting effect, can effectively cover the wound surface, and is more conducive to wound healing. Adding a certain amount of hydrophilic polymer allows the second drug to have a suitable release rate.

[0037] The fiber dressing of the present invention is composed of micro-nano fibers with a core-shell structure. The outer shell of the fiber contains a first drug that promotes macrophage polarization, which can promote the polarization of macrophages on normal wounds and diabetic wounds from the pro-inflammatory M1 type to the anti-inflammatory M2 type; the matrix of the outer shell is a mixture of hydrophilic polymers and hydrophobic polymers, which can absorb exudate at the wound surface to achieve a "dissolution-infiltration-adhesion" effect. By spraying non-irritating physiological saline, the fiber membrane can be effectively peeled off, achieving controllable wet adhesion and reducing secondary damage to the wound surface; the inner core contains a second drug that induces the death of M1 macrophages, which can reduce the number of M1 macrophages, reduce the inflammatory response of the wound surface, and accelerate the healing of the wound surface. Healing; the inner core also contains a third drug, which can effectively kill bacteria on the wound and reduce the degree of infection on the wound; the matrix of the inner core is a mixture of hydrophilic polymers and hydrophobic polymers with good biocompatibility, which can provide mechanical support for the fiber dressing and provide a sustained-release effect for the two substances in the inner core; controlling the type ratio of hydrophilic polymers, hydrophobic polymers and drugs in the outer shell and the inner core can adjust the release rate of the drug and further promote wound healing. At the same time, the fiber dressing has excellent biocompatibility, non-irritation and the ability to promote the proliferation of endothelial cells and fibroblasts. It can achieve non-irritation, on-demand controllable adhesion on the wound, and has the characteristics of non-irritation adhesion and easy peeling, and controlled drug release rate.

[0038] The present invention also provides a method for preparing the fiber dressing for promoting wound healing described in the above technical solution, which includes coaxial electrospinning, near-field direct writing, microfluidic spinning or immersion pulling, preferably coaxial electrospinning.

[0039] In the present invention, the coaxial electrospinning method preferably comprises the following steps:

[0040] (1) mixing a first hydrophilic polymer, a first hydrophobic polymer, a first drug, and a first solvent to obtain a shell spinning solution;

[0041] (2) mixing a second hydrophilic polymer, a second hydrophobic polymer, a second drug, a third drug, and a second solvent to obtain a core spinning solution;

[0042] (3) coaxially electrospinning the shell spinning solution obtained in step (1) and the core spinning solution obtained in step (2) to obtain a fiber dressing that promotes wound healing;

[0043] There is no chronological order for steps (1) and (2).

[0044] Unless otherwise specified, the present invention has no particular limitation on the sources of the raw materials, and commercially available products known to those skilled in the art may be used.

[0045] In the present invention, the first hydrophilic polymer, the first hydrophobic polymer, the first drug and the first solvent are preferably mixed to obtain the shell spinning solution.

[0046] In the present invention, the first solvent preferably includes dimethylformamide (DMF) and anhydrous ethanol; the mass ratio of DMF to anhydrous ethanol is preferably (8-10):1, more preferably 9:1. By limiting the composition and ratio of the first solvent to the above range, the present invention can improve the spinnability of electrospinning.

[0047] In the present invention, the mass concentration of the first hydrophilic polymer in the shell spinning solution is preferably 1.5-15%. The present invention limits the mass concentration of the first hydrophilic polymer in the shell spinning solution to the above range, which can make it fully dissolved and more conducive to electrospinning.

[0048] In the present invention, the mass ratio of the first hydrophilic polymer, the first hydrophobic polymer, and the first drug in the shell spinning solution is preferably (1-10):1:(0.1-0.5), more preferably (3-10):1:(0.1-0.5), and even more preferably (5-10):1:(0.1-0.5). By controlling the mass ratio of the first hydrophilic polymer, the first hydrophobic polymer, and the first drug in the shell spinning solution, the present invention can control the adhesion strength of the fiber dressing shell and the release rate of the first drug, thereby making the fiber dressing more conducive to wound healing.

[0049] The present invention has no particular limitation on the mixing operation of the first hydrophilic polymer, the first hydrophobic polymer, the first drug and the first solvent. The raw materials can be uniformly mixed using mixing techniques well known to those skilled in the art.

[0050] In the present invention, the second hydrophilic polymer, the second hydrophobic polymer, the second drug, the third drug and the second solvent are preferably mixed to obtain the core spinning solution.

[0051] In the present invention, when the third drug is silver nanoparticles, the present invention preferably adds a metal salt of the third drug, that is, a silver salt. In the present invention, the silver salt is preferably silver nitrate.

[0052] In the present invention, when the third drug is copper nanoparticles, the present invention preferably adds a metal salt of the third drug, that is, a copper salt. In the present invention, the copper salt is preferably copper nitrate.

[0053] In the present invention, the second solvent preferably includes DMF and tetrahydrofuran; the mass ratio of DMF to tetrahydrofuran is preferably (1-2):1, more preferably (1-1.5):1. By limiting the composition and ratio of the second solvent to the above range, the present invention can improve the spinnability of electrospinning.

[0054] In the present invention, the mass concentration of the second hydrophilic polymer in the core spinning solution is preferably 1.5-7.5%. The present invention limits the mass concentration of the second hydrophilic polymer in the core spinning solution to the above range, which can ensure the mechanical strength of the core while also regulating the release rate of the second drug and the third drug.

[0055] In the present invention, when the third drug is directly added, the mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug and the third drug in the core spinning solution is preferably 1: (1-10): (0.1-0.5): (0.1-0.2).

[0056] In the present invention, when a metal salt of a third drug is added, the mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug, and the metal salt of the third drug in the core spinning solution is preferably 1:(1-10):(0.1-0.5):(0.1-0.3). By limiting the mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug, and the third drug or the metal salt of the third drug in the core spinning solution to the above range, the present invention can regulate the release rate of the second and third drugs while maintaining the mechanical strength of the core, thereby achieving better anti-wound infection and anti-inflammatory effects, making the fiber dressing more conducive to wound healing.

[0057] After obtaining the shell spinning solution and the core spinning solution, the present invention preferably performs coaxial electrospinning on the shell spinning solution and the core spinning solution to obtain a fiber dressing that promotes wound healing.

[0058] In the present invention, the ambient temperature during the coaxial electrospinning is preferably 30-40°C; the ambient humidity during the coaxial electrospinning is preferably 20-40 RH%. The present invention limits the ambient temperature and humidity to the above ranges, which can quickly volatilize the solvent in the spinning solution and avoid adhesion between fibers.

[0059] In the present invention, during the coaxial electrospinning, the flow rate of the outer shell spinning solution is preferably 0.6 to 1.5 mL / h, more preferably 0.8 to 1.2 mL / h; during the coaxial electrospinning, the flow rate of the inner core spinning solution is preferably 0.2 to 1.2 mL / h, more preferably 0.4 to 1.0 mL / h; and during the coaxial electrospinning, the flow rate ratio of the outer shell spinning solution to the inner core spinning solution is preferably (1 to 6): 1. The present invention can adjust the thickness ratio of the outer shell to the inner core in the fiber dressing by adjusting the flow rate ratio of the outer shell spinning solution to the inner core spinning solution during coaxial electrospinning.

[0060] In the present invention, the voltage of the coaxial electrospinning is preferably 15-20 kV, more preferably 18 kV; the receiving distance of the coaxial electrospinning is preferably 20-25 cm, more preferably 21 cm; and the coaxial electrospinning time is 1-5 hours, more preferably 2-4 hours. In the coaxial electrospinning process, the silver salt or copper salt is reduced by DMF to silver nanoparticles or copper nanoparticles, which serve as the third agent. By limiting the coaxial electrospinning parameters to the above ranges, the present invention is more conducive to obtaining fibers with uniform thickness and regular morphology.

[0061] In the present invention, a hydrophobic spray is preferably sprayed on the receiving device before the coaxial electrospinning. The present invention does not specifically limit the type or amount of the hydrophobic spray, as long as it ensures smooth fiber release from the surface of the receiving device. In the present invention, the hydrophobic spray is preferably a superhydrophobic silica nanoparticle spray.

[0062] After the coaxial electrospinning is completed, the present invention preferably dries the coaxial electrospinning product to obtain a fiber dressing that promotes wound healing.

[0063] In the present invention, the drying temperature is preferably 30 to 50° C., more preferably 40° C.; the drying time is preferably 12 to 36 hours, more preferably 24 hours.

[0064] The present invention has no special limitation on the specific operation of the near-field direct writing method, microfluidic spinning method or immersion pulling method, and the technical solutions well known to those skilled in the art can be adopted.

[0065] The present invention also provides the use of the fiber dressing for promoting wound healing described in the above technical solution or the fiber dressing for promoting wound healing prepared according to the preparation method described in the above technical solution in the preparation of wound dressing.

[0066] In the present invention, the wound surface is preferably a diabetic wound surface.

[0067] The fiber dressing provided by the present invention has excellent biocompatibility, antibacterial properties, is non-irritating, and has controllable adhesion, so that the prepared wound dressing has an excellent wound healing-promoting effect.

[0068] The present invention has no special limitation on the operation of using the fiber dressing in preparing wound dressing, and the application technical solutions well known to those skilled in the art can be adopted.

[0069] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0070] The polyvinyl pyrrolidone and polycaprolactone used in each example were purchased from Sigma-Aldrich, and DMF, anhydrous ethanol and tetrahydrofuran were purchased from Aladdin Biological Reagent Company.

[0071] Example 1

[0072] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 9:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:9:0.33:0.13.

[0073] The preparation method of the fiber dressing is as follows:

[0074] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 15%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 9:1:0.3;

[0075] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 13.4%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:9:0.33:0.2;

[0076] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 1.0 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 1.2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and dried in an oven at 45°C for 24 h to obtain a fiber dressing.

[0077] Example 2

[0078] The flow rate of the core spinning solution in step (3) of Example 1 was replaced with 0.8 mL / h. At this time, the flow rate ratio of the shell spinning solution to the core spinning solution was 1.5:1. Other parameters were the same as in Example 1 to obtain a fiber dressing.

[0079] Example 3

[0080] The flow rate of the core spinning solution in step (3) of Example 1 was replaced with 0.6 mL / h. At this time, the flow rate ratio of the shell spinning solution to the core spinning solution was 2:1. The other parameters were the same as those in Example 1, and a fiber dressing was obtained, which was recorded as CUR / AS+Ag-loaded.

[0081] Example 4

[0082] The flow rate of the core spinning solution in step (3) of Example 1 was replaced with 0.4 mL / h. At this time, the flow rate ratio of the shell spinning solution to the core spinning solution was 3:1. Other parameters were the same as those in Example 1 to obtain a fiber dressing.

[0083] Example 5

[0084] The flow rate of the core spinning solution in step (3) of Example 1 was replaced with 0.2 mL / h. At this time, the flow rate ratio of the shell spinning solution to the core spinning solution was 6:1. Other parameters were the same as in Example 1 to obtain a fiber dressing.

[0085] Example 6

[0086] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 8:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:9:0.33:0.13.

[0087] The preparation method of the fiber dressing is as follows:

[0088] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 13.6%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 8:1:0.3;

[0089] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 13.4%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:9:0.33:0.2;

[0090] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 0.6 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and placed in an oven at 45°C for drying for 24 h to obtain a fiber dressing.

[0091] Example 7

[0092] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 4:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:9:0.33:0.13.

[0093] The preparation method of the fiber dressing is as follows:

[0094] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 6.8%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 4:1:0.3;

[0095] (2) to (3) are the same as in Example 6.

[0096] Example 8

[0097] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 2:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:9:0.33:0.13.

[0098] The preparation method of the fiber dressing is as follows:

[0099] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 3.4%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 2:1:0.3;

[0100] (2) to (3) are the same as in Example 6.

[0101] Example 9

[0102] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1.5:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:9:0.33:0.13.

[0103] The preparation method of the fiber dressing is as follows:

[0104] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 2.55%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1.5:1:0.3;

[0105] (2) to (3) are the same as in Example 6.

[0106] Example 10

[0107] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:9:0.33:0.13.

[0108] The preparation method of the fiber dressing is as follows:

[0109] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.7%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1:1:0.3;

[0110] (2) to (3) are the same as in Example 6.

[0111] Example 11

[0112] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:8:0.33:0.13.

[0113] The preparation method of the fiber dressing is as follows:

[0114] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.7%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1:1:0.3;

[0115] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 12%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:8:0.33:0.2;

[0116] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 0.6 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and placed in an oven at 45°C for drying for 24 h to obtain a fiber dressing.

[0117] Example 12

[0118] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:4:0.33:0.13.

[0119] The preparation method of the fiber dressing is as follows:

[0120] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.7%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1:1:0.3;

[0121] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 6%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:4:0.33:0.2;

[0122] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 0.6 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and placed in an oven at 45°C for drying for 24 h to obtain a fiber dressing.

[0123] Example 13

[0124] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:2:0.33:0.13.

[0125] The preparation method of the fiber dressing is as follows:

[0126] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.7%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1:1:0.3;

[0127] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 3%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:2:0.33:0.2;

[0128] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 0.6 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and placed in an oven at 45°C for drying for 24 h to obtain a fiber dressing.

[0129] Example 14

[0130] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:1.5:0.33:0.13.

[0131] The preparation method of the fiber dressing is as follows:

[0132] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.7%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1:1:0.3;

[0133] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 2.25%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:1.5:0.33:0.2;

[0134] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 0.6 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and placed in an oven at 45°C for drying for 24 h to obtain a fiber dressing.

[0135] Example 15

[0136] A fiber dressing for promoting wound healing, comprising micro-nano fibers with a core-shell structure, wherein the outer shell of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), and curcumin; the inner core of the fibers comprises polyvinyl pyrrolidone (average molecular weight 360,000 Da), polycaprolactone (average molecular weight 18,000 Da), asiaticoside, and silver nanoparticles; the mass ratio of polyvinyl pyrrolidone, polycaprolactone, and curcumin in the outer shell is 1:1:0.3; and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside, and silver nanoparticles in the inner core is 1:1:0.33:0.13.

[0137] The preparation method of the fiber dressing is as follows:

[0138] (1) polyvinyl pyrrolidone, polycaprolactone, curcumin, DMF and anhydrous ethanol are mixed to obtain a shell spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.7%, the mass concentration of polycaprolactone is 1.7%, the mass concentration of curcumin is 0.5%, the mass ratio of DMF to anhydrous ethanol is 9:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone and curcumin in the shell spinning solution is 1:1:0.3;

[0139] (2) polyvinyl pyrrolidone, polycaprolactone, asiaticoside, silver nitrate, DMF and tetrahydrofuran are mixed to obtain a core spinning solution, wherein the mass concentration of polyvinyl pyrrolidone is 1.5%, the mass concentration of polycaprolactone is 1.5%, the mass concentration of asiaticoside is 0.5%, the mass concentration of silver nitrate is 0.3%, the mass ratio of DMF to tetrahydrofuran is 1.05:1, and the mass ratio of polyvinyl pyrrolidone, polycaprolactone, asiaticoside and silver nitrate in the core spinning solution is 1:1:0.33:0.2;

[0140] (3) The ambient temperature was controlled at 35°C, and the ambient humidity was controlled at 25 RH%. A hydrophobic spray was sprayed on the receiving device of the electrospinning machine. The coaxial electrospinning pillow was placed 21 cm away from the receiving end. The flow rate of the outer shell spinning solution was 1.2 mL / h, and the flow rate of the inner core spinning solution was 0.6 mL / h (the flow rate ratio of the outer shell spinning solution to the inner core spinning solution was 2:1). The voltage was increased by 18 kV to form a Taylor cone at the needle tip. The electrospinning was performed for 3 h. The fiber membrane was removed from the receiving end and placed in an oven at 45°C for drying for 24 h to obtain a fiber dressing.

[0141] Comparative Example 1

[0142] Curcumin, asiaticoside, and silver nanoparticles in Example 3 were omitted, and other parameters were the same as those in Example 3 to obtain a blank fiber dressing, which was recorded as No-loaded.

[0143] Comparative Example 2

[0144] The asiaticoside and silver nanoparticles in the core of Example 3 were omitted, and other parameters were the same as those in Example 3, thereby obtaining a fiber dressing containing curcumin only in the shell, which was denoted as CUR-loaded.

[0145] Comparative Example 3

[0146] The curcumin in the shell and the silver nanoparticles in the core of Example 3 were omitted, and other parameters were the same as those in Example 3, thereby obtaining a fiber dressing containing only asiaticoside in the core, which was recorded as AS-loaded.

[0147] Comparative Example 4

[0148] The curcumin in the shell and the asiaticoside in the core of Example 3 were omitted, and other parameters were the same as those of Example 3, thereby obtaining a fiber dressing containing only silver nanoparticles in the core, which was denoted as Ag-loaded.

[0149] Test Example 1: Appearance and morphology test

[0150] The macroscopic optical image, microscopic SEM image and SEM image of a single broken fiber of the fiber dressing in Example 3 are shown in FIG. Figure 1 As shown. Figure 1 It can be seen that the fiber dressing in Example 3 is composed of micro-nano fibers, and the micro-nano fibers have a core-shell structure. The presence of curcumin makes the fiber dressing appear yellow in appearance.

[0151] Test Example 2: Biocompatibility Test

[0152] The fiber dressings in Example 3 and Comparative Examples 1 to 4 and a 20% mass concentration of dimethyl sulfoxide solution were co-cultured with high-glucose aged human umbilical vein endothelial cells (HUVECs), human fibroblasts (HDFs), and mouse macrophages (RAW264.7s), and CCK8 cytotoxicity assays were performed. The results are as follows: Figures 2-4 As shown, Figure 2 The graphs show the cytotoxicity of the fiber dressings in Example 3 and Comparative Examples 1 to 4 to HUVECs; Figure 3 The graphs show the cytotoxicity of the fiber dressings in Example 3 and Comparative Examples 1 to 4 to HDFs; Figure 4 Figures 3 and 4 are cytotoxicity graphs of the fiber dressings in Example 3 and Comparative Examples 1 to 4 on RAW264.7s at different culture days, wherein A is the cytotoxicity graph of the fiber dressings in Example 3 and Comparative Examples 1 to 4 on RAW264.7s on the first culture day (Day 1); and B is the cytotoxicity graph of the fiber dressings in Example 3 and Comparative Examples 1 to 4 on the third culture day (Day 3). Figures 2-3 From left to right in the figure are control group, comparative example 1, comparative example 2, comparative example 3, comparative example 4, embodiment 3 and 20% DMSO group.

[0153] from Figures 2-4 It can be seen that the fiber dressing provided by the present invention does not cause the death of HUVECs and HDFs in a high-sugar microenvironment after being co-cultured with them for 24 hours. When co-cultured with RAW264.7s for 24 hours, there is no obvious cytotoxicity. However, when the fiber dressing is co-cultured with RAW264.7s for 72 hours, the activity of RAW264.7s is significantly reduced. These results show that the fiber dressing provided by the present invention has good biocompatibility for skin repair-related cells. The polarizing drugs released in the first stage do not affect the activity of macrophages, while the drugs released in the second stage will significantly reduce the activity of macrophages, achieving further anti-inflammatory effects.

[0154] Test Example 3: Macrophage Polarization Experiment

[0155] First, M1 macrophages were obtained by lipopolysaccharide (LPS) treatment, and the construction method was as follows: macrophages (RAW264.7) were planted in a high-glucose medium containing 25mM glucose and 10% fetal bovine serum containing 100ng / mL LPS and cultured for 24h. Secondly, a RAW264.7 polarization experiment was carried out, and RAW264.7 was planted in a 24-well plate and divided into 5 groups. Equal amounts of the fiber dressings of Example 3 and Comparative Examples 1 to 4 were added to the RAW264.7 culture medium, with 3 replicates in each group. The expression of CD86 and CD206 molecules was detected by cell immunofluorescence. CD86 (green) represents M1 macrophages, and CD206 (red) represents M2 macrophages. The results are as follows Figure 5 shown.

[0156] from Figure 5 As can be seen, only Comparative Example 2 and Example 3 significantly promote the polarization of M1 macrophages to M2 macrophages, with a significant increase in the number of red cells and a significant decrease in the number of green cells. This is due to the dissolution of the polarization-promoting drug carried in the outer phase of the fiber dressing into the cell culture medium, inducing the polarization of M1 macrophages to M2 macrophages. Comparative Example 3 and Example 3 show a slight decrease in the number of RAW264.7 cells, which is attributed to the effect of the carried drug that induces macrophage cell death.

[0157] Test Example 4: Inhibition Zone Experiment

[0158] Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were respectively 7 CFU / mL was coated on an agar plate. The fiber dressings of Example 3 and Comparative Examples 1 to 4 (sterile, 10 mm in diameter, 500 μm in thickness) were carefully applied to the agar plate evenly coated with bacteria. The plates were cultured at 37°C for 24 h. The diameter of the inhibition zone was observed by taking photos (optical image) and quantitatively analyzed (histogram). The results are shown in Table 1. Figure 6 As shown, Figure 6 A is the diameter of the inhibition zone of the fiber dressing of Example 3 and Comparative Examples 1 to 4 against E. coli (optical image); B is a quantitative statistical graph of the antibacterial performance of the fiber dressing of Example 3 and Comparative Examples 1 to 4 against E. coli; C is the diameter of the inhibition zone of the fiber dressing of Example 3 and Comparative Examples 1 to 4 against S. aureus (optical image); D is a quantitative statistical graph of the antibacterial performance of the fiber dressing of Example 3 and Comparative Examples 1 to 4 against S. aureus. Figure 6 It can be seen that Comparative Example 4 and Example 3 both have obvious antibacterial activity against E. coli, and the diameters of the inhibition zones are significantly larger than those of the other groups; similarly, they also have obvious antibacterial activity against S. aureus, and the diameters of the inhibition zones are significantly larger than those of the other groups.

[0159] Test Example 5: In vitro non-stimulation on-demand controllable adhesion test

[0160] A clean glass slide (3 cm long, 1 cm wide) was attached to the tensile testing machine test table with double-sided tape. Different volumes of ultrapure water were evenly distributed on the glass slide. The fiber membrane in Example 3 (5 cm long, 1 cm wide, 500 μm thick) was pressed onto the water-coated glass substrate with a preload of 5 N. The adhesion strength of the fiber dressing in Example 3 on surfaces with different water contents was then examined using a 90° peeling method. The results are shown in Figure 2. Figure 7 shown.

[0161] from Figure 7 It can be seen that when the substrate water content is 15uL, the fiber dressing has a higher peel strength, about 1.5N / cm. As the substrate water content increases, the peel strength of the fiber dressing gradually decreases, indicating that the fiber dressing has a non-irritating, on-demand controllable adhesion effect.

[0162] Test Example 6: In vivo non-stimulation on-demand controllable adhesion experiment

[0163] C57 mice were anesthetized with 1 wt% sodium pentobarbital, and full-thickness skin defects with a diameter of 10 mm were cut on the back of the mice using ophthalmic scissors. The fiber membrane in Example 3 (5 cm long, 4 cm wide, 500 μm thick) was taken and its middle part was applied to the wound surface. After standing for 30 seconds, the fiber membrane in Example 3 was gradually lifted. At the same time, the mouse was not fixed with other measures. The height of the mouse was observed. After that, a large amount of physiological saline was dripped on the wound surface. The peeling process of the fiber dressing was observed. The results are shown in the figure. Figure 8 shown.

[0164] from Figure 8 It can be seen from the figure that dressings can be easily changed by spraying normal saline on the wound surface without damaging the wound surface and surrounding tissues, thereby reducing secondary damage during dressing changes.

[0165] Test Example 7: Effect of Promoting Wound Healing of Full-Thickness Skin Defects in Diabetic Mice

[0166] Thirty 7-week-old female diabetic mice were randomly divided into 5 groups. After anesthesia with 3% sodium pentobarbital, two full-thickness skin defect wounds with a diameter of 10 mm were constructed on the back of the mice. Then, 100 μL of 1×10 7CFU / mL of Staphylococcus aureus liquid was used to create an infectious diabetic wound model. The wound was then covered with the fiber membranes of Example 3 and Comparative Examples 1 to 4, respectively, and the mice were raised in the same environment. The wounds were photographed on days 0, 3, 7, 10, and 14 (optical images), and the wound healing speed was calculated (quantitative images). On days 3 and 7 after injury, the wound tissue was taken and ground to obtain a tissue homogenate. The number of bacteria present in the wound was analyzed by agarose plating method (optical images). The results are shown in FIG. Figure 9 shown.

[0167] from Figure 9 It can be seen that the wounds of the infectious diabetic mice that applied Example 3 healed the fastest, and the wounds were basically closed 14 days after the injury, while the wounds of the other groups of control groups healed at a slower rate, and there were still obvious unclosed areas on the wounds after 14 days. This shows that Example 3 has a significant effect in promoting the healing of diabetic wounds. At the same time, wound tissue was taken and it was found that the number of bacteria in the wounds that applied Example 3 was the least 3 days after the injury, and the bacteria almost disappeared 7 days after the injury. However, there were still more bacteria in the other control groups. This shows that Example 3 has excellent antibacterial activity in vivo.

[0168] In summary, the fiber dressing provided by the present invention has excellent biocompatibility, controllable adhesion, antibacterial properties, multi-stage immune regulation, and excellent wound healing effect.

[0169] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A fiber dressing for promoting wound healing, comprising micro-nano fibers having a core-shell structure; the outer shell of the fibers comprises a first hydrophilic polymer, a first hydrophobic polymer, and a first drug; the inner core of the fibers comprises a second hydrophilic polymer, a second hydrophobic polymer, a second drug, and a third drug; the first drug is curcumin; the second drug is asiaticoside; and the third drug is silver nanoparticles; The mass ratio of the first hydrophilic polymer, the first hydrophobic polymer and the first drug in the shell is (1-10):1:(0.1-0.5); The mass ratio of the second hydrophilic polymer, the second hydrophobic polymer, the second drug and the third drug in the core is 1:(1-10):(0.1-0.5):(0.1-0.2); The first hydrophilic polymer and the second hydrophilic polymer are polyvinyl pyrrolidone; The first hydrophobic polymer and the second hydrophobic polymer are polycaprolactone.

2. The method for preparing the fiber dressing for promoting wound healing according to claim 1 comprises a coaxial electrospinning method, a near-field direct writing method, a microfluidic spinning method or an immersion pulling method.

3. Use of the fiber dressing for promoting wound healing according to claim 1 or the fiber dressing for promoting wound healing prepared according to the preparation method according to claim 2 in the preparation of wound dressings.

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