Composite dressing with continuous unidirectional moisture conduction capability and preparation method thereof

Abstract

The present invention provides a composite dressing with continuous unidirectional moisture conduction capability and a preparation method thereof, wherein a hydrophobic silk fiber membrane and a hydrophilic electrospun cellulose membrane are respectively arranged on both sides of a super absorbent sponge to obtain a unidirectional moisture conduction dressing, and then a graphene oxide dispersion is evenly sprayed onto the surface of one side of the hydrophilic electrospun cellulose membrane to obtain the composite dressing. The present invention realizes unidirectional continuous transport of exudate through a hierarchical multi-level pore structure jointly constructed by a hydrophobic layer, a hydrophilic sponge and a hydrophilic layer containing graphene oxide.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and in particular relates to a composite dressing with continuous unidirectional moisture conduction capability and a preparation method thereof. Background Art

[0002] As we all know, the skin is a natural barrier between the human body and the external environment. Trauma is inevitable in daily life. The choice of dressings largely determines the speed and quality of wound healing. Traditional theoretical studies have shown that a moist microenvironment is conducive to wound repair, which has led to the rapid development of hydrophilic dressings. When the wound is in the inflammatory stage, histamine increases the permeability of capillaries, resulting in excessive exudate from the wound. Wound exudate contains a variety of substances, including water, nutrients, proteases, cytokines, cytokines, growth factors, etc. High levels of proteases in wound exudate delay wound healing by interfering with the proliferation of keratinocytes, fibroblasts and endothelial cells. Traditional moist dressings such as gauze are still prone to repeated infiltration of the wound by tissue exudate after partial absorption of the effusion, resulting in an over-hydrated state, which significantly affects the wound repair process. In addition, hydrophilic gauze has a good affinity for cells and will adhere to the skin tissue, which can easily cause secondary wound damage when replaced.

[0003] Currently, negative pressure wound treatment is commonly used in clinic to drain exudate from the wound site, thereby effectively preventing wound fluid accumulation, but this treatment method is expensive and painful. Therefore, the management of exudate has become a technical problem in this field. Summary of the invention

[0004] In order to solve the problems in the prior art, the present invention realizes unidirectional continuous transport of exudate through a layered multi-level pore structure jointly constructed by a hydrophobic layer, a hydrophilic sponge and a hydrophilic layer containing graphene oxide, and provides a composite dressing with continuous unidirectional moisture conduction capability and a preparation method thereof.

[0005] The present invention solves the technical problem by adopting the following technical solutions:

[0006] The first object of the present invention is to provide a method for preparing a composite dressing with continuous unidirectional moisture-conducting ability, characterized in that a hydrophobic silk fiber membrane and a hydrophilic electrospun cellulose membrane are respectively arranged on both sides of a super absorbent sponge to obtain a unidirectional moisture-conducting dressing, and then a graphene oxide dispersion is evenly sprayed onto the surface of one side of the hydrophilic electrospun cellulose membrane to obtain the composite dressing.

[0007] Furthermore, the super absorbent sponge is a polysaccharide-dialdehyde starch sponge, a gelatin sponge, a silk sponge or a cellulose sponge.

[0008] Furthermore, the polysaccharide-dialdehyde starch sponge is a prefabricated liquid obtained by mixing amino polysaccharide, polysaccharide polymer and dialdehyde starch, and is obtained after freeze-drying.

[0009] Furthermore, the hydrophobic silk fiber membrane is laid on the bottom of the superabsorbent sponge pre-liquid before drying, and the hydrophilic electrospun cellulose membrane is laid on the top, and the hydrophilic electrospun cellulose membrane is fixed on the surface of the superabsorbent sponge pre-liquid by tin foil, and after freeze-drying, the tin foil is peeled off to obtain the unidirectional moisture-conducting dressing.

[0010] Furthermore, the preparation method of the polysaccharide-dialdehyde starch pre-liquid is: dissolving amino polysaccharide powder in acetic acid solution under stirring, then adding polysaccharide polymer and continuing to stir until it becomes a uniform paste, and then adding dialdehyde starch solution and stirring to obtain the polysaccharide-dialdehyde starch pre-liquid.

[0011] Further, the aminopolysaccharide is chitosan, hydroxyethyl chitosan, hydroxymethyl chitosan, hydroxypropyl chitosan, hydroxybutyl chitosan, hyaluronic acid or other chitosans. Preferably, the aminopolysaccharide is chitosan.

[0012] Furthermore, the polysaccharide polymer is konjac glucomannan.

[0013] Furthermore, the electrospun silk fiber membrane obtained by the electrospinning process is immersed in anhydrous ethanol and dried naturally to obtain the hydrophobic silk fiber membrane.

[0014] Furthermore, the preparation process of the silk electrospun fiber membrane is as follows: after the shredded silkworm cocoons are degummed in a sodium carbonate solution in a water bath, they are washed with deionized water and dried in an oven, and then added to a lithium bromide solution with a solid-liquid ratio of 1:16 for dissolution in a water bath, filtered, dialyzed in deionized water, and freeze-dried to obtain a silk sponge; the silk sponge is dissolved in an organic solvent, and the silk electrospun fiber membrane is obtained by an electrostatic spinning process.

[0015] Furthermore, the hydrophilic electrospun cellulose membrane is a cellulose acetate electrospun fiber membrane.

[0016] Furthermore, the preparation method of the cellulose acetate electrospun fiber membrane is: dissolving cellulose acetate in acetone and N,N-dimethylformamide and stirring until completely dissolved to obtain a spinning solution, and obtaining the cellulose acetate electrospun fiber membrane by an electrostatic spinning process.

[0017] The second object of the present invention is to provide a composite dressing prepared by the above method with continuous unidirectional moisture conduction capability.

[0018] Furthermore, the composite dressing includes a hydrophobic silk fiber membrane layer, a super absorbent sponge layer, a hydrophilic electrospun cellulose membrane layer and a graphene oxide layer.

[0019] Furthermore, the composite dressing is applied in a near-infrared light environment.

[0020] Compared with the prior art, the beneficial technical effects of the present invention are:

[0021] The present invention introduces a sponge with strong water absorption and water retention as an intermediate layer, which can temporarily store a large amount of exudate. Compared with the conventional Janus structure composed of polyurethane hydrophobic fiber membrane and hydrophilic fiber membrane, the present invention adds a "water storage layer" that can continuously transport exudate in large quantities, so that the dressing can adapt to wounds with more exudate. The super hydrophilicity of the sponge layer can also play a pumping role, and the asymmetric wettability of the sponge layer and the hydrophobic fiber membrane can efficiently and continuously transport exudate in a directional manner, thereby maintaining an ideal microenvironment of the wound that is moist but not wet.

[0022] The present invention also adds a graphene oxide layer with good photothermal effect. The graphene oxide generates a large amount of heat under the irradiation of near-infrared light (808nm), which increases the temperature of the dressing and thus evaporates the exudate out of the sponge layer. After arranging a hydrophobic silk fiber membrane and a hydrophilic electrospun cellulose membrane on both sides of the super absorbent sponge, a unidirectional moisture-conducting dressing is obtained to achieve continuous output of wound exudate.

[0023] The material with good photothermal effect for increasing the temperature of the dressing in the present invention is not limited to graphene oxide. Other materials with good photothermal effect can also be used in the present invention. For example, black phosphorus can also replace graphene oxide and cooperate with the dressing to achieve continuous output of wound exudate.

[0024] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention, it can be implemented according to the contents of the specification. In order to make the above and other purposes, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The present invention is a preparation flow chart of a composite dressing with continuous unidirectional moisture conduction capability and a preparation method thereof.

[0026] Figure 2 This is an infrared thermal imaging image of different fiber membranes in a composite dressing with continuous unidirectional moisture conduction capability and a preparation method of the present invention under near-infrared light.

[0027] Figure 3 This is a diagram showing the diffusion and penetration of red ink on a hydrophobic silk film and a cellulose acetate film in a composite dressing with continuous unidirectional moisture conduction capability and a preparation method of the present invention.

[0028] Figure 4This is a live-dead double-stained fluorescence image of mouse fibroblasts in a composite dressing with continuous unidirectional moisture conduction capability and a preparation method of the present invention.

[0029] Figure 5 This is a schematic diagram of wound exudate management in a composite dressing with continuous unidirectional moisture conduction capability and a preparation method of the present invention. DETAILED DESCRIPTION

[0030] The technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be understood that the following embodiments are only exemplary illustrations and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope of protection that the present invention is intended to protect.

[0031] In addition, unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0032] A method for preparing a composite dressing with continuous unidirectional moisture conduction capability, comprising: arranging a hydrophobic silk fiber membrane and a hydrophilic electrospun cellulose membrane on both sides of a super absorbent sponge to obtain a unidirectional moisture conduction dressing, and then spraying a graphene oxide dispersion evenly onto the surface of one side of the hydrophilic electrospun cellulose membrane to obtain a composite dressing.

[0033] A hydrophobic silk fiber membrane is arranged on one side of the upper and lower sides of the super absorbent sponge, and a hydrophilic electrospun cellulose membrane is arranged on the other side. When in use, one side of the hydrophobic silk fiber membrane is in contact with the skin, and the asymmetric wettability gradient effect is used to drive the exudate to transfer from the hydrophobic part to the hydrophilic part, so as to achieve directional movement of the exudate, and make the composite dressing have the function of unidirectional moisture conduction. Different from the conventional Janus structure dressing, a super absorbent sponge is arranged between the hydrophobic silk fiber membrane and the hydrophilic electrospun cellulose membrane to form a water storage layer, which can absorb and temporarily store a large amount of exudate, and transport the exudate to the hydrophilic electrospun fiber membrane, avoiding long-term infiltration of the wound due to the poor water storage capacity of the hydrophilic layer. At the same time, graphene oxide is sprayed on the surface of the hydrophilic electrospun cellulose membrane, and under the near-infrared light environment, the exudate derived from the hydrophilic electrospun cellulose membrane absorbs a large amount of heat, causing the exudate to evaporate and promote the continuous transport of the exudate.

[0034] In a preferred embodiment, the super absorbent sponge is a polysaccharide-dialdehyde starch sponge, a gelatin sponge, a silk sponge or a cellulose sponge. The polysaccharide-dialdehyde starch sponge is a preformed liquid obtained by mixing amino polysaccharide, polysaccharide polymer and dialdehyde starch, and is obtained by freeze-drying.

[0035] In order to fix the superabsorbent sponge to the hydrophobic layer and the hydrophilic layer to obtain a unidirectional dressing, a hydrophobic silk fiber membrane is laid on the bottom of the superabsorbent sponge preformed liquid before drying, and a hydrophilic electrospun cellulose membrane is laid on the top, and the hydrophilic electrospun cellulose membrane is fixed to the surface of the superabsorbent sponge preformed liquid by tin foil. After freeze-drying, the tin foil is peeled off to obtain a unidirectional moisture-conducting dressing.

[0036] A composite dressing with continuous unidirectional moisture conduction capability prepared by the above method.

[0037] In a specific embodiment, the composite dressing includes a hydrophobic silk fiber membrane layer, a super absorbent sponge layer, a hydrophilic electrospun cellulose membrane layer and a graphene oxide layer.

[0038] In practical applications, the hydrophobic silk fiber membrane layer is in contact with the skin, and its hydrophobic properties can keep the skin contact surface dry, preventing the wound from being in an overly moist microenvironment and hindering wound healing. For wounds with a lot of exudate, near-infrared photothermal irradiation is assisted, and the photothermal effect of graphene oxide causes the hydrophilic electrospun cellulose membrane layer to heat up rapidly, evaporating the exudate out of the super absorbent sponge layer, achieving continuous delivery of wound exudate, thereby maintaining an ideal microenvironment of the wound that is moist but not wet, accelerating wound healing.

[0039] In a specific embodiment, the composite dressing with continuous unidirectional moisture conduction capability of the present invention can also be used in combination with various drugs or antimicrobial agents that promote wound healing.

[0040] Embodiment 1:

[0041] See attached Figure 1 A method for preparing a composite dressing with continuous unidirectional moisture conduction capability comprises the following steps:

[0042] 1) Preparation of silk electrospun fiber membrane

[0043] Preparation of silk electrospun fiber membrane using condition parameters and operation steps: 20g of shredded silk cocoons were placed in a beaker containing 500mL of 0.5% (w / v) sodium carbonate solution, and degummed for 1h in a 100℃ water bath, stirring from time to time during the period to allow the silk cocoons to fully contact with the solution. After the treatment, they were repeatedly soaked and washed in deionized water until there was no silkiness, and then dried in a 60℃ oven for 24h. The degummed silk cocoons were added to a 9mol / L lithium bromide solution at a solid-liquid ratio of 1:16, dissolved in a 60℃ water bath for 4h, filtered through 8 layers of gauze, dialyzed in deionized water (DW=3500) for 3 days, and freeze-dried for 48h to obtain a silk sponge.

[0044] Weigh 0.5 g of freeze-dried silk sponge, dissolve it in 10 mL of hexafluoroisopropanol under magnetic stirring at room temperature for 1 h to prepare the silk electrospinning solution. Use high-voltage electrospinning process, set spinning parameters: needle inner diameter 0.6 mm, extrusion speed 0.6 mL / h, voltage 20 kV, spinning distance 15 cm, use a roller wrapped tightly with tin foil as the receiving device, and continuously electrospin for 8 h at 25 ° C and humidity 40% to obtain the silk electrospun fiber membrane.

[0045] 2) Post-treatment of silk electrospun fiber membrane - to achieve the transformation of the fiber membrane from hydrophilic to hydrophobic.

[0046] The silk electrospun fiber membrane was soaked in anhydrous ethanol for 7 hours, then taken out and dried naturally at room temperature.

[0047] 3) Preparation of hydrophilic cellulose acetate electrospun fiber membrane

[0048] Weigh 2.25g of cellulose acetate, dissolve it in 10mL of acetone and 5mL of N,N-dimethylformamide, and stir it magnetically at room temperature for 0.5h until it is completely dissolved to obtain a spinning solution. Use a high-voltage electrospinning process, set the spinning parameters: needle inner diameter 0.5mm, extrusion speed 0.6mL / h, voltage 16kV, spinning distance 15cm, use a roller wrapped tightly with tin foil as the receiving device, and continuously electrospin at 25℃ and humidity 40% to obtain a cellulose acetate electrospun fiber membrane.

[0049] 4) Preparation of chitosan / konjac glucomannan / dialdehyde starch sponge

[0050] 1 g of chitosan powder was weighed and dissolved in 50 mL of 0.6% (v / v) acetic acid solution under mechanical stirring for 5 min. Then, 1 g of konjac glucomannan was added and stirred for 2 min until it became a uniform paste. Finally, 1 mL of 1% (w / v) dialdehyde starch solution was added and stirred for 2 min to obtain a chitosan / konjac glucomannan / dialdehyde starch sponge pre-liquid.

[0051] 5) Preparation of composite dressings - assembly of hierarchical pore structures and spraying of graphene oxide.

[0052] The silk fiber membrane obtained in step 2) and treated with ethanol was placed at the bottom of the container, and an appropriate amount of chitosan / konjac glucomannan / dialdehyde starch sponge prefabricated solution obtained in step 4) was added, and then the cellulose acetate membrane obtained in step 3) was placed on the top, and the hydrophilic cellulose acetate membrane was fixed on the surface of the super absorbent sponge prefabricated solution through tin foil, and then freeze-dried after standing at room temperature for half an hour, and the tin foil at both ends of the material was removed after demoulding to obtain a unidirectional moisture-conducting dressing. Finally, the ultrasonically dispersed dispersion containing 2 mg of graphene oxide was evenly sprayed on the surface of the cellulose acetate membrane, and a composite dressing was obtained after drying at room temperature.

[0053] In a specific embodiment, the chitosan in the super absorbent sponge in Example 1 can be replaced by hydroxyethyl chitosan, hydroxymethyl chitosan, hydroxypropyl chitosan, hydroxybutyl chitosan, hyaluronic acid or other chitosans, and konjac glucomannan can be replaced by other polysaccharide polymers, with the same technical effects.

[0054] In a specific embodiment, the graphene oxide in Example 1 can be replaced by other photothermal effect materials to generate a large amount of heat under the irradiation of near-infrared light, thereby increasing the temperature of the dressing to evaporate the exudate out of the sponge layer, thereby achieving continuous output of wound exudate.

[0055] Experimental Example 1:

[0056] The silk electrospun fiber membrane obtained in step 2) of Example 1, the cellulose acetate electrospun fiber membrane obtained in step 3) and the composite dressing sprayed with graphene oxide obtained in step 5) were respectively irradiated with near-infrared light at 808 nm for 1 min, and infrared thermal images of the three fiber membranes were observed using an infrared thermal imager. The results are shown in the attached drawings. Figure 2 .

[0057] From the attached Figure 2 It can be seen that the surface temperature of the composite dressing loaded with graphene oxide rises rapidly, reaching a certain temperature within 6 seconds, and the temperature range gradually expands with time, which is conducive to the evaporation of exudate.

[0058] Experimental Example 2:

[0059] A drop of red ink was added to the surface of the silk electrospun fiber membrane obtained in step 2) of Example 1 and the cellulose acetate electrospun fiber membrane obtained in step 3) respectively, and the diffusion and penetration of the droplets on the two fiber membranes were observed. Figure 3 This is a diagram showing the diffusion and penetration of red ink on two fiber membranes.

[0060] It can be seen that the silk electrospun fiber membrane treated with ethanol has good hydrophobicity, and the red ink does not show obvious diffusion. Combined with the side view, it can be seen that the red ink quickly penetrates the silk electrospun fiber membrane. After 6S, the red ink has basically penetrated the silk electrospun fiber membrane. The red ink on the cellulose acetate electrospun fiber membrane quickly spreads, forming a large area of ​​ink marks, which are absorbed by the cellulose acetate electrospun fiber membrane and have a slow penetration rate.

[0061] Experimental Example 3:

[0062] The culture medium of the cultured mouse fibroblasts was dried and rinsed with a buffer solution. The unidirectional moisture-conducting dressing obtained in step 5) of Example 1 without spraying graphene oxide and the composite dressing obtained by spraying graphene oxide were respectively covered on the bottom of the culture dish. The culture dish not covered with any dressing was used as a control sample. Two fluorescent dyes, calcein AM and propidium iodide PI, were added to stain live cells and dead cells at the same time. The double staining results were observed with a fluorescence microscope. See the attached Figure 4 , where live cells are green and dead cells are red.

[0063] It can be seen that the unidirectional moisture-conducting dressing has very good biocompatibility and can promote cell proliferation with obvious proliferation effect. The number of living cells in the composite dressing sprayed with graphene oxide is reduced compared with the unidirectional moisture-conducting dressing not sprayed with graphene oxide, but there is still a considerable number of cell proliferation, which shows that the composite dressing sprayed with graphene oxide still has good biocompatibility.

[0064] In addition, by establishing an animal skin full defect model to test the wound healing ability, the experiment proved that the composite dressing of the present application greatly improved the healing quality compared with conventional dressings. This is mainly because the fiber membrane prepared by electrospinning technology has a unique submicron effect, providing a high specific surface area and high porosity, and better simulating the framework structure of the extracellular matrix; coupled with the asymmetric wettability, the exudate is transferred from the hydrophobic silk membrane side to the hydrophilic cellulose acetate membrane side, and evaporated under the photothermal effect of graphene oxide, thereby providing an ideal microenvironment for the wound to be moist but not wet, accelerating the process of wound repair.

[0065] The serial numbers of the above embodiments of the present invention are only for description and do not represent the advantages or disadvantages of the embodiments.

[0066] The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above-mentioned specific implementation modes, which are merely illustrative rather than restrictive. Under the guidance of the present invention, ordinary technicians in this field can also make many forms without departing from the scope of protection of the present invention and the claims, all of which are within the protection of the present invention.

Claims

1. A method for preparing a composite dressing with continuous unidirectional moisture conduction capability, characterized in that: A unidirectional moisture-conducting dressing is obtained by respectively arranging a hydrophobic silk fiber membrane and a hydrophilic electrospun cellulose membrane on both sides of a super absorbent sponge, and then a graphene oxide dispersion is evenly sprayed onto the surface of one side of the hydrophilic electrospun cellulose membrane to obtain the composite dressing; the super absorbent sponge is a polysaccharide-dialdehyde starch sponge; The preparation method of the polysaccharide-dialdehyde starch sponge is as follows: dissolving amino polysaccharide powder in acetic acid solution under stirring, then adding polysaccharide polymer and continuing to stir until it becomes a uniform paste, adding dialdehyde starch solution and stirring to obtain the polysaccharide-dialdehyde starch pre-liquid, and freeze-drying to obtain.

2. A method for preparing a composite dressing with continuous unidirectional moisture conduction capability as claimed in claim 1, characterized in that: The hydrophobic silk fiber membrane is laid on the bottom of the superabsorbent sponge preformed liquid before drying, and the hydrophilic electrospun cellulose membrane is laid on the top, and the hydrophilic electrospun cellulose membrane is fixed on the surface of the superabsorbent sponge preformed liquid by tin foil. After freeze-drying, the tin foil is peeled off to obtain the unidirectional moisture-conducting dressing.

3. A method for preparing a composite dressing with continuous unidirectional moisture conduction capability as claimed in claim 1, characterized in that: The electrospun silk fiber membrane obtained by the electrospinning process is immersed in anhydrous ethanol and dried naturally to obtain the hydrophobic silk fiber membrane.

4. A method for preparing a composite dressing with continuous unidirectional moisture conduction capability as claimed in claim 3, characterized in that: The preparation process of the silk electrospun fiber membrane is as follows: the chopped silkworm cocoons are degummed in a sodium carbonate solution in a water bath, washed with deionized water, dried in an oven, added to a lithium bromide solution with a solid-liquid ratio of 1:16 for dissolution in a water bath, filtered, dialyzed in deionized water, and freeze-dried to obtain a silk sponge; the silk sponge is dissolved in an organic solvent, and the silk electrospun fiber membrane is obtained by an electrostatic spinning process.

5. A method for preparing a composite dressing with continuous unidirectional moisture conduction capability as claimed in claim 1, characterized in that: The hydrophilic electrospun cellulose membrane is a cellulose acetate electrospun fiber membrane. The preparation method of the cellulose acetate electrospun fiber membrane is: dissolving cellulose acetate in acetone and N,N-dimethylformamide and stirring until completely dissolved to obtain a spinning solution, and using an electrostatic spinning process to obtain the cellulose acetate electrospun fiber membrane.

6. A composite dressing having continuous unidirectional moisture conduction capability obtained according to the preparation method according to any one of claims 1 to 5.

7. A composite dressing with continuous unidirectional moisture conduction capability as claimed in claim 6, characterized in that: The composite dressing comprises a hydrophobic silk fiber membrane layer, a super absorbent sponge layer, a hydrophilic electrospun cellulose membrane layer and a graphene oxide layer.

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