Wound healing promoting medical dressing and preparation method thereof

Abstract

The invention discloses a wound healing promoting medical dressing and a preparation method thereof. The wound healing promoting medical dressing comprises a stent, gel and an active component, the stent comprises a film covering layer and a supporting layer, wherein first fiber filaments are arranged in a disordered mode, and fiber bundles are arranged in the supporting layer according to a structure forming a parallelogram grid. The fiber bundle is composed of at least six independent second fiber filaments; the active component comprises a growth factor. The growth factors can participate in wound repair, and the healing time is shortened; the stent is of a two-layer structure, the film covering layer provides a sealing effect for the supporting layer and the gel body, and leakage of active substances and pollution of foreign substances are avoided while breathability is guaranteed; the multi-strand structure fiber bundles of the supporting layer have high strength, high flexibility and fatigue resistance, and are arranged in a parallelogram to provide anisotropic mechanical properties for the wound healing promoting medical dressing, so that the dressing can actively adapt to stress / strain changes of a skin lesion position when a patient moves, and the adhesion stability of the dressing and the skin lesion position is enhanced.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine and biomaterials, and in particular to a wound healing-promoting medical dressing and a preparation method thereof. Background Art

[0002] The extracellular matrix of specific cells (such as stem cells, fibroblasts, and keratinocytes) contains a variety of active factors that can promote wound healing. Therefore, cell therapy for skin lesions has been a research hotspot. However, studies have shown that cells proliferating in vitro can become cancerous, posing a potential risk for direct contact between cells and the body. Therefore, developing a method to efficiently extract active substances from cells for wound treatment is of great significance.

[0003] In addition, the dressings in the prior art usually exhibit isotropic mechanical properties, which do not conform to the anisotropic mechanical structure characteristics of human skin. Therefore, they are prone to falling off when subjected to stress and strain, have poor safety in use, and are prone to causing secondary damage to the lesion site.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] The present invention provides a wound healing promoting medical dressing and a preparation method thereof. The wound healing promoting medical dressing has good mechanical properties and mechanical safety and can effectively promote wound healing.

[0006] The present invention is achieved in that:

[0007] In a first aspect, the present invention provides a wound healing-promoting medical dressing comprising a scaffold, a gel and an active ingredient; the scaffold comprises a coating layer in which first fiber filaments are arranged in a disordered manner and a supporting layer in which fiber bundles are arranged in a structure forming a parallelogram grid; the fiber bundles are composed of at least 6 separate second fiber filaments; and the active ingredient comprises a growth factor.

[0008] The wound healing medical dressing provided by the present invention has growth factors that can participate in wound repair and shorten the healing time; in addition, the support of the dressing has a two-layer structure, and the volume density of the coating layer is greater than that of the supporting layer and is arranged in a disordered manner, providing a sealing effect for the supporting layer and the gel, ensuring air permeability while avoiding leakage of active substances and contamination by foreign substances; the supporting layer is composed of fiber bundles with a multi-strand structure arranged in a parallelogram shape. The fibers with a multi-strand structure have higher strength, softness and fatigue resistance than fibers with a single-strand structure, thereby improving the mechanical strength, mechanical safety and cyclic performance of the supporting layer; in addition, the fiber bundles are arranged in a parallelogram shape to provide the wound healing medical dressing with anisotropic mechanical properties, so that it conforms to the physical properties of muscles, and therefore has better conformity to the surface of human skin, so that the dressing can actively adapt to the stress / strain changes at the lesion site during patient exercise, enhance the adhesion stability between the dressing and the lesion site, and avoid secondary damage to the lesion site caused by the dressing falling off during patient exercise.

[0009] In some embodiments, the longitudinal to transverse stiffness ratio of the stent is 1.5 to 3, wherein the longitudinal to transverse stiffness ratio refers to the ratio of the Young's modulus of the stent in the longitudinal and transverse directions; a stent that meets this longitudinal to transverse stiffness ratio conforms to the strength anisotropy of human skin, can adapt to skin stress / strain changes, and enhance the adhesion stability of the dressing to the lesion location.

[0010] In some embodiments, the second fiber filaments include a conductive agent; preferably, the conductive agent is selected from at least one of silver, polypyrrole, graphene, carbon nanotubes, and carbon nanowires; the addition of the conductive agent allows the dressing to be combined with exogenous electrical stimulation therapy to promote wound healing, especially for patients with chronic wounds, whose skin impedance makes simple dressings less effective. The application of exogenous electrical stimulation to simulate the natural current at the wound can promote blood flow, increase tissue oxygenation, promote cell proliferation and migration, angiogenesis, and collagen deposition, thereby promoting wound healing and improving the therapeutic effect. Compared to the prior art, which incorporates a conductive agent into the gel, the present invention's composite conductive agent in the scaffold can reduce the migration of the conductive agent, reduce toxicity and irritation to the wound surface, and ensure the stability and continuity of the electrical conductivity, avoiding the influence of the gel's water absorption and expansion.

[0011] In some embodiments, the gel is made of one or more of the following materials: polyvinyl alcohol or its derivatives, polyacrylic acid or its derivatives, collagen or its derivatives, gelatin or its derivatives, hyaluronic acid or its derivatives, alginate or its derivatives, chitosan or its derivatives, cellulose derivatives, carbomer, polyethylene oxide. In the present invention, the functions of the gel include the following: (1) serving as a carrier for active substances such as growth factors; (2) absorbing exudate from the lesion; and (3) providing a warm and humid environment for the wound surface. Therefore, any gel that can provide the above effects can achieve the effects of the present invention.

[0012] In some embodiments, the porosity of the scaffold is 60% to 80%. The wound healing medical dressing provided by the present invention has a high porosity and can support and absorb more gel while meeting mechanical properties, thereby providing a larger pore structure for loading active substances, such as growth factors.

[0013] In some embodiments, the pore size of the scaffold ranges from 2 to 15 μm; and the ratio of the sum of the pore volumes of pores with a pore size of 8 μm or less to the sum of the pore volumes of pores with a pore size of 15 μm or less is greater than 80%.

[0014] When the porosity is similar, a wound-healing medical dressing with a greater proportion of small-diameter pores and smaller large-diameter pores exhibits improved sealing capabilities. Excessively large pores can lead to the penetration of foreign contaminants and leakage of contents. Furthermore, the wound-healing medical dressing has a pore size range of 2 to 15 μm, and the ratio of the sum of the pore volumes of pores with a pore size of 8 μm or less to the sum of the pore volumes of pores with a pore size of 15 μm or less is greater than 80%. Meeting these conditions allows the scaffold to provide a superior sealing effect on the growth factor-loaded gel, preventing leakage and providing superior mechanical stability.

[0015] In some embodiments, the growth factors include at least one of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), transforming growth factor-β2 (TGF-β2), transforming growth factor-β3 (TGF-β3), insulin-like growth factor I (IGF-1), and insulin-like growth factor II (IGF-2). These growth factors are active substances in the extracellular matrix and can promote skin tissue repair.

[0016] In some embodiments, the active ingredient is derived from an extracellular matrix derived from at least one of human fibroblasts, bone marrow mesenchymal stem cells, adipose-derived mesenchymal stem cells, and skin keratinocytes. Cell therapy is currently a hot topic in wound healing and repair research. The extracellular matrix of specific cells contains substances that promote wound healing, such as growth factors, collagen fibers, elastic fibers, reticular fibers, and hyaluronic acid. The extracellular matrix contained in the in situ-grown cells in the dressing can maximize the diversity, activity, and content of the active ingredients.

[0017] In some embodiments, the scaffold satisfies at least one of the following features 1 to 7:

[0018] Feature 1: The average cross-sectional diameter of the first fiber is 1 to 2 μm;

[0019] Feature 2: The first fiber filament comprises at least one of polyester, polylactic acid, polyglycolic acid, and polyurethane; wherein the polyester comprises at least one of polycaprolactone, polyglycerol sebacate, polybutylene adipate / terephthalate, polybutylene succinate terephthalate, β-hydroxybutyric acid and β-hydroxyvalerate copolymer, and lactide / caprolactone copolymer;

[0020] Feature 3: The fiber bundle includes 6 to 36 individual second fiber filaments;

[0021] Feature 4: The average cross-sectional diameter of the second fiber is 5 to 12 μm;

[0022] Feature 5: The second fiber filament comprises at least one of the following polymers: polyester, polylactic acid, polyglycolic acid, and polyurethane; the polyester comprises at least one of polycaprolactone, polyglycerol sebacate, polybutylene adipate / terephthalate, polybutylene succinate terephthalate, β-hydroxybutyric acid and β-hydroxyvalerate copolymer, and lactide / caprolactone copolymer;

[0023] Feature 6: The longest diagonal of the parallelogram is 400-600 μm, the ratio of the length of the longest diagonal to the shortest diagonal is 1.2-1.4, and the minimum angle between the longest diagonal and the shortest diagonal is 45-90°;

[0024] Feature 7: The volume density of the coating layer is 0.06-0.15 g / cm 3 .

[0025] The present invention can adjust the mechanical properties and anisotropy of the wound healing medical dressing by adjusting the parameters of the parallelogram and the number, diameter and raw material type of the second fiber filaments, so as to adapt it to different application scenarios.

[0026] In a second aspect, the present invention provides a method for preparing the wound healing promoting medical dressing according to any of the above embodiments, comprising the following steps:

[0027] S1: Preparation of scaffolds

[0028] S1.1 spinning the first polymer 1 and pressing it to prepare a coating layer;

[0029] S1.2 Using the coating layer as a receiving substrate, spinning the sea component and the island component by melt electrospinning according to a set program to obtain a sea-island fiber felt in which the sea-island fibers are arranged in a parallelogram structure;

[0030] S1.3 reducing the sea-island fiber felt and drying it to obtain a bracket;

[0031] S2: Preparation of gel scaffold complex

[0032] The scaffold is placed at the bottom of the mold, a casting solution is poured, solidified and freeze-dried to obtain a gel-scaffold complex;

[0033] S3: Preparation of wound healing medical dressings

[0034] The living cells are inoculated onto the gel scaffold complex for culture, and then subjected to a second freeze-drying process to obtain a wound healing-promoting medical dressing.

[0035] The present invention first prepares a scaffold, then composites it with a gel and undergoes a first freeze-drying process to prepare a carrier with a rich pore structure. The carrier is then used as a culture dish to culture cells. As the cells proliferate, more and more extracellular matrix grows in situ, so that the gel-scaffold complex is loaded with a large amount of active substances, thereby improving bioavailability. The second freeze-drying process then inactivates the cells while maintaining the activity of the active substances, thereby avoiding the problem of cancerous transformation caused by cell proliferation in vitro.

[0036] The present invention combines melt electrospinning direct writing technology and composite spinning technology to prepare a support layer composed of orderly arranged fiber bundles with multiple structures. This method is simple and highly controllable. The selection of polymer components and their proportions, the design of fiber arrangement, and the adjustment of spinning conditions during the spinning process can regulate the various properties of wound healing medical dressings.

[0037] In some embodiments, the above preparation method satisfies at least one of the following characteristics I to IV:

[0038] Feature I: The first polymer comprises at least one of polyester, polylactic acid, and polyurethane, wherein the polyester comprises at least one of polycaprolactone, polyglycerol sebacate, and lactide / caprolactone copolymer;

[0039] Feature II: The sea component includes a second polymer, and the second polymer includes at least one of polyvinyl alcohol and polymethylpyrrolidone;

[0040] Feature III: The island component includes a third polymer; the third polymer includes at least one of polyester, polylactic acid, and polyurethane; wherein the polyester includes at least one of polycaprolactone, polyglycerol sebacate, polyhydroxybutyrate, and lactide / caprolactone copolymer;

[0041] Feature IV: The island component includes a third polymer and a conductive agent; the third polymer includes at least one of polyester, polylactic acid and polyurethane; wherein the polyester includes at least one of polycaprolactone, polyglycerol sebacate, polyhydroxybutyrate and lactide / caprolactone copolymer; the conductive agent includes at least one of silver, polypyrrole, graphene, carbon nanotubes and carbon nanowires.

[0042] In some embodiments, the above preparation method satisfies at least one of the following features V to XI:

[0043] Feature V: The mass ratio of the second polymer to the third polymer is 1:1.2-1.6;

[0044] Feature VI: The number of islands in the sea-island fiber is 6 to 36;

[0045] Feature VII: The conductive agent accounts for 0.5% to 1.5% by mass of the island component;

[0046] Feature VIII: The spinning 1 is solution spinning or melt spinning;

[0047] Feature IX: The pressing comprises pressing the fiber felt obtained by spinning 1 into a coating layer with a target bulk density of 0.06 to 0.15 g / cm 3 ;

[0048] Feature X: The melt electrospinning writing (MEW) method comprises: flowing a molten polymer through a nozzle to form a melt stream, which is stretched under the action of an electrostatic field and guided onto a movable receiver to form a desired fiber structure;

[0049] Feature XI: The reduction refers to removing the second polymer in water.

[0050] In some embodiments, the casting solution includes a high molecular weight polymer; the high molecular weight polymer is selected from one or more of polyvinyl alcohol or its derivatives, polyacrylic acid or its derivatives, collagen or its derivatives, gelatin or its derivatives, hyaluronic acid or its derivatives, alginate or its derivatives, chitosan or its derivatives, cellulose derivatives, carbomer and polyethylene oxide.

[0051] In some embodiments, the casting solution includes a polymer and a cross-linking agent; the casting solution includes a polymer; the polymer is selected from one or more of polyvinyl alcohol or its derivatives, polyacrylic acid or its derivatives, collagen or its derivatives, gelatin or its derivatives, hyaluronic acid or its derivatives, alginate or its derivatives, chitosan or its derivatives, cellulose derivatives, carbomer and polyethylene oxide; the cross-linking agent is selected from at least one of glutaraldehyde, genipin, hexanediol diglycidyl ether, calcium salt, transglutaminase, laccase and peroxidase.

[0052] In some embodiments, the mass percentage content of the high molecular weight polymer in the casting solution is 5% to 40%.

[0053] In some embodiments, the amount of the casting solution added is determined so that the mass ratio of the gel-scaffold complex to the scaffold is 0.3-0.5:1.

[0054] In some embodiments, the first freeze-drying condition is freeze-drying at -60 to -80°C and a vacuum degree of 1 to 10 Pa for 24 to 48 hours.

[0055] In some embodiments, the temperature of the second freeze-drying is not lower than -30°C.

[0056] In some embodiments, the curing refers to static crosslinking at 25-80° C. or radiation crosslinking.

[0057] In a third aspect, the present invention further provides a melt electrospinning direct writing device, comprising: an upper cover plate and a lower cover plate, a fiber microscope camera connected to the lower end of the upper cover plate, a melt insulation chamber fixed to the lower end of the upper cover plate and a spinning assembly provided at the bottom; an X-direction guide rail and a Y-direction guide rail are provided at the upper end of the lower cover plate, and a Z-direction guide rail is provided at the lower end of the lower cover plate and passes through the lower cover plate; a jet microscope camera bracket and a receiving plate bracket are respectively fixed to the X-direction guide rail, and a jet microscope camera and a receiving plate are respectively fixed to the upper ends of the jet microscope camera bracket and the receiving plate bracket; the jet microscope camera and the fiber microscope camera are connected to a computer through a control element; a voltage is connected between the spinning assembly and the receiving plate to form a high-voltage electrostatic field;

[0058] The melt insulation chamber is provided with a barrel 1 and a barrel 2, and the outer walls of the barrel 1 and the barrel 2 are respectively provided with an electromagnetic heating coil 1 and an electromagnetic heating coil 2. The upper ends of the barrel 1 and the barrel 2 are respectively provided with openings and pass through the upper cover plate. The double-channel air compressor is connected to the upper end openings of the barrel 1 and the barrel 2 respectively through a conduit; the lower ends of the barrel 1 and the barrel 2 are respectively provided with openings and connected to the spinning assembly through a conduit;

[0059] The spinning assembly includes a blanking plate, a distribution plate, a needle plate, a pinhole plate and a spinneret; the blanking plate is provided with an island component feed hole and a sea component feed hole penetrating the blanking plate; the distribution plate is provided with an island component flow channel and a sea component flow channel;

[0060] The needle plate includes an island component receiving hole, a sea component flow guide and a needle tube group; the island component receiving hole is opened on the upper surface of the needle plate and is recessed therein; the needle tube group is formed in the needle plate so as to be connected with the island component receiving hole; the island component receiving hole and the needle tube group are arranged above and below each other, and the needle tube group includes a plurality of needle tubes; the sea component flow guide includes a plurality of receiving holes provided on the upper surface of the needle plate and recessed therein, a groove portion on the lower surface of the needle plate and recessed therein, and a plurality of material guide holes between the receiving holes and the groove portion;

[0061] The pinhole plate is provided with island holes and side holes penetrating the pinhole plate, the island holes corresponding to each needle tube one by one, and the side holes are arranged around the island holes; the upper end diameter of the island holes is larger than the diameter of the needle tube; and the groove portion extends to communicate with the side holes;

[0062] The spinneret is provided with a spinneret hole which penetrates the spinneret and is connected with the island hole and the side hole. The spinneret hole has a cone portion and a discharge hole portion which is located below the cone portion and is connected with the cone portion.

[0063] Melt electrospinning writing (MEW) involves flowing a molten polymer through a nozzle to form a melt stream, which is stretched under the action of an electrostatic field and directed onto a movable receiver to form a desired fiber structure.

[0064] The set program refers to a program for controlling the moving speed and displacement of the collector so that the fiber filaments on the receiver are arranged in a parallelogram structure.

[0065] The present invention has the following beneficial effects:

[0066] (1) The wound healing medical dressing provided by the present invention includes a scaffold, a gel and a growth factor; the growth factor can participate in wound repair and shorten the healing time; the scaffold of the dressing has a two-layer structure, the volume density of the coating layer is greater than that of the support layer and is arranged in a disordered manner, providing a sealing effect for the support layer and the gel, ensuring air permeability while avoiding leakage of active substances and contamination by foreign substances; the support layer is composed of fiber bundles with a multi-strand structure arranged in a parallelogram shape, and the fibers with a multi-strand structure have higher strength, softness and fatigue resistance than those with a single-strand structure, thereby improving the mechanical strength, mechanical safety and cyclic performance of the support layer; in addition, the fiber bundles are arranged in a parallelogram shape to provide the wound healing medical dressing with anisotropic mechanical properties, making it consistent with the physical properties of muscles, so that it has better conformity to the surface of human skin, so that the dressing can actively adapt to the stress / strain changes at the skin lesion site during patient exercise, enhance the adhesion stability between the dressing and the skin lesion site, and avoid secondary damage to the skin lesion site caused by the dressing falling off during patient exercise.

[0067] (2) The present invention provides a method for preparing a wound healing medical dressing, wherein a scaffold is first prepared, and then compounded with a gel and subjected to a first freeze-drying process to obtain a carrier having a rich porous structure. The carrier is then used as a culture dish to culture cells. As the cells proliferate, more and more extracellular matrix grows in situ, so that a large amount of active substances are loaded into the gel scaffold complex, thereby improving bioavailability. The cells are then inactivated by a second freeze-drying process, while the activity of the active substances is maintained, thereby avoiding the problem of cancerous changes caused by cell proliferation in vitro. The present invention prepares a support layer composed of an orderly arrangement of fiber bundles having a multi-strand structure by combining melt electrospinning direct writing technology and composite spinning technology. The method is simple and highly controllable. The selection of polymer components and their proportions during the spinning process, the design of the fiber arrangement method, the adjustment of the spinning conditions, etc. can regulate the various properties of the wound healing medical dressing. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0069] Figure 1 This is a schematic structural diagram of the wound healing promoting medical dressing prepared in Example 2 of the present invention;

[0070] Figure 2 Schematic diagram of the structure of the melt electrospinning direct writing device according to Example 8 of the present invention;

[0071] Figure 3 Schematic diagram of the structure of the melt holding chamber in Example 8 of the present invention;

[0072] Figure 4 This is a schematic structural diagram of the spinning assembly of Example 8 of the present invention.

[0073] In the figure: 1. Upper cover; 2. Lower cover; 3. Fiber microscope camera; 4. Melt holding chamber; 5. Spinning assembly; 61. X-direction guide rail; 62. Y-direction guide rail; 63. Z-direction guide rail; 7. Fluid microscope camera bracket; 71. Fluid microscope camera; 8. Receiving plate bracket; 81. Receiving plate; 9. Computer; 10. Dual-channel air compressor; 411. Barrel 1; 412. Barrel 2; 421. Electromagnetic heating coil 1; 422. Electromagnetic heating coil 2; 51. Blanking plate; 52, distribution plate; 53, needle plate; 51, pinhole plate; 55, spinneret; 511, island component feed hole; 512, sea component feed hole; 521, island component diversion channel; 522, sea component diversion channel; 531, island component receiving hole; 532, sea component guide channel; 5321, receiving hole; 5322, guide hole; 5323, groove part; 533, needle tube group; 5331, needle tube; 541, island hole; 542, side hole; 551 spinneret. DETAILED DESCRIPTION

[0074] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0075] In the description of the embodiments of this application, technical terms such as "first" and "second" are only used to distinguish different objects and cannot be understood as indicating or implying relative importance or implicitly indicating the number, specific order or primary and secondary relationship of the indicated technical features.

[0076] Reference herein to an "embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present application. The appearance of the phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive with other embodiments.

[0077] In the embodiment of the present application, the term "or / and" is only a description of the association relationship of associated objects, indicating that three relationships may exist. For example, A or / and B can represent three situations: A exists alone, A and B exist at the same time, and B exists alone.

[0078] In addition, the character “ / ” in this article generally indicates that the previous and next related objects are in an “or” relationship.

[0079] In the embodiments of the present application, "multiple" means more than two (including two). Similarly, "multiple groups" means more than two groups (including two groups), and "multi-layer" means more than two layers (including two layers), unless otherwise clearly specified and limited.

[0080] In the embodiments of the present application, “at least one” means one or more than one.

[0081] Those skilled in the art may understand the specific meanings of the above terms in the embodiments of this application based on specific circumstances.

[0082] The features and performance of the present invention are further described in detail below with reference to the embodiments.

[0083] Example 1

[0084] A method for preparing a wound healing-promoting medical dressing comprises the following steps:

[0085] S1: Preparation of scaffolds

[0086] S1.1 Polycaprolactone (average molecular weight 5×10 4 The average diameter of the fiber was 1.65 μm and the surface density was 41.22 g / m 2 The fiber felt was then hot-pressed at 60°C and then cold-pressed to obtain a bulk density of 0.094 g / cm 3 coating layer.

[0087] S1.2 The coating layer is used as the receiving substrate, the mixed masterbatch of polycaprolactone and nanosilver is used as the island component and the mixed masterbatch of polymethyl pyrrolidone (average molecular weight of 10 5 g / mol) as the sea component, and a melt electrospinning direct writing device was used for composite spinning to obtain a sea-island fiber felt;

[0088] The island-in-the-sea fiber was prepared by the island-fixing method, with 16 islands.

[0089] The mass percentage of nanosilver (average particle size of 200 nm, purchased from Beijing Zhongke Keyou Technology Co., Ltd.) in the mixed masterbatch of polycaprolactone and nanosilver is 1%, and the masterbatch is prepared by the following method: polyester lactone particles and nanosilver are melt-blended at 150° C. using a conical twin-screw extruder, and the mixture is cooled and granulated after extrusion.

[0090] The materials were added according to a mass ratio of the second polymer in the sea component to the third polymer in the island component of 1:1.4.

[0091] The melt electrospinning apparatus was programmed to arrange the extruded island-in-the-sea fibers in a parallelogram grid. The longest diagonal of the parallelogram was 500 μm, the ratio of the longest to shortest diagonal lengths was 1.3, and the minimum angle between the longest and shortest diagonals was 80°. The spinning distance was 4 mm, the spin pack temperature was maintained at 230°C, the spinning voltage was 2 kV, and the nozzle movement speed was set at 400 mm / min.

[0092] S1.3 The sea-island fiber felt was placed in an aqueous solution and heated to 60°C for oscillation reaction for 3 hours. The wound healing medical dressing precursor was obtained after removal and drying. Microscopic observation showed that the average cross-sectional diameter of the second fiber filaments (island fibers) was 8.25 μm.

[0093] S2: Preparation of gel scaffold complex

[0094] S2.1 Collagen, sodium alginate, and hydroxyethyl cellulose are mixed in a mass ratio of 10:4:2 to obtain a polymer, and the polymer and glutaraldehyde are dissolved in ultrapure water in a mass ratio of 1:0.02 to form a casting solution having an 8% polymer content, and citric acid is added to adjust the pH of the casting solution to 6.4;

[0095] S2.2 Place the scaffold at the bottom of the mold, pour the casting liquid, heat to 75°C and let it stand for 6 hours to solidify, then freeze-dry to obtain a gel scaffold complex; control the amount of casting liquid added so that the mass ratio of the gel scaffold complex to the scaffold is (0.4±0.05):1; the freeze-drying conditions are as follows: freeze-dry for 24 hours at a temperature of -80°C and a vacuum degree of 1Pa.

[0096] S3: Preparation of wound healing medical dressings

[0097] Adipose-derived mesenchymal stem cells (purchased from Sichuan New Life Stem Cell Technology Co., Ltd.) were seeded on the gel scaffold complex after UV disinfection and sterilization at a seeding density of 10 4 pieces / cm 2 , cultured in a 36°C, 5% carbon dioxide incubator for 10 days, with the culture medium replaced once a day; then freeze-dried to obtain a wound healing-promoting medical dressing;

[0098] The freeze-drying conditions are as follows: pre-cooling at -30°C for 2 hours, then sublimation drying at -10°C under a vacuum degree of 10 Pa for 5 hours; and sublimation drying and heat preservation at 0°C for 12 hours.

[0099] Example 2

[0100] This embodiment provides a wound healing promoting medical dressing, the structure of which is as shown in the attached figure. Figure 1As shown, it includes a scaffold and a gel loaded with active substances. The scaffold includes a coating layer in which fiber filaments 1 are arranged in a disordered manner and a supporting layer in which fiber bundles 2 are arranged in a parallelogram grid structure. The fiber bundle 2 is composed of 6 individual fiber filaments 22.

[0101] The preparation method of the wound healing-promoting medical dressing comprises the following steps:

[0102] S1: Preparation of scaffolds

[0103] S1.1 Polycaprolactone (average molecular weight 5×10 4 g / mol) and polylactic acid (average molecular weight 3×10 4 g / mol) in a mass ratio of 1:3 was used for electrospinning of a mixed solution (the solvent was N,N'-dimethylformamide) to prepare fibers with an average diameter of 1.05 μm and an area density of 44.94 g / m 2 The fiber felt was then hot-pressed at 60°C and then cold-pressed to obtain a bulk density of 0.138 g / cm 3 coating layer.

[0104] S1.2 The film layer is used as the receiving substrate, and polyglycolic acid (average molecular weight 3×10 4 g / mol) and carbon nanotubes (NC700, purchased from Shanghai Xiyan Technology Service Center) as the island component and polyvinyl alcohol (average molecular weight of 8×10 4 g / mol) as the sea component, and a melt electrospinning direct writing device was used for composite spinning to obtain a sea-island fiber felt;

[0105] The island-in-the-sea fiber was prepared by the island-fixing method, and the number of islands was 6;

[0106] The mass percentage of carbon nanotubes in the mixed masterbatch of polyglycolic acid and carbon nanotubes is 0.5%, and the masterbatch is prepared by the following method: polyglycolic acid and carbon nanotube powder are melt-blended at 220° C. using a conical twin-screw extruder, and then cooled and granulated after extrusion.

[0107] The materials were added according to a mass ratio of the second polymer in the sea component to the third polymer in the island component of 1:1.6.

[0108] The melt electrospinning apparatus was programmed to arrange the extruded island-in-the-sea fibers in a parallelogram grid. The longest diagonal of the parallelogram was 500 μm, the ratio of the longest to shortest diagonal lengths was 1.3, and the minimum angle between the longest and shortest diagonals was 80°. The spinning distance was 4 mm, the spin pack temperature was maintained at 230°C, the spinning voltage was 2 kV, and the nozzle movement speed was set at 400 mm / min.

[0109] S1.3 The sea-island fiber felt was placed in an aqueous solution and heated to 60°C for oscillation reaction for 3 hours. The wound healing medical dressing precursor was obtained after removal and drying. Microscopic observation showed that the average cross-sectional diameter of the fiber filaments 22 (island fibers) was 10.11 μm.

[0110] S2: Preparation of gel scaffold complex

[0111] S2.1. Mix gelatin and sodium hyaluronate in a mass ratio of 10:1.2 to obtain a polymer. Dissolve the polymer in 1× PBS buffer and add transglutaminase at a ratio of 5 U transglutaminase per 1 g of gelatin to form a casting solution with a polymer content of 15%.

[0112] S2.2 Place the scaffold at the bottom of the mold, pour the casting liquid, heat to 50°C and let it stand for 24 hours to solidify, then freeze-dry to obtain a gel scaffold complex; control the amount of casting liquid added so that the mass ratio of the gel scaffold complex to the scaffold is (0.4±0.05):1; the freeze-drying conditions are as follows: freeze-dry for 24 hours at a temperature of -80°C and a vacuum degree of 1Pa.

[0113] S3: Preparation of wound healing medical dressings

[0114] Human fibroblasts (purchased from Pronocell Life Sciences Co., Ltd.) were seeded on the gel scaffold complex after UV disinfection and sterilization at a seeding density of 10 6 pieces / cm 2 , cultured in a 36°C, 5% carbon dioxide incubator for 8 days, with the culture medium replaced once a day; then freeze-dried to obtain a wound healing-promoting medical dressing;

[0115] The freeze-drying conditions are as follows: pre-cooling at -30°C for 2 hours, then sublimation drying at -10°C under a vacuum degree of 10 Pa for 5 hours; and sublimation drying and heat preservation at 0°C for 12 hours.

[0116] Example 3

[0117] A method for preparing a wound healing-promoting medical dressing comprises the following steps:

[0118] S1: Preparation of scaffolds

[0119] S1.1 Polycaprolactone and polybutylene adipate / terephthalate (PBAT, melt flow rate of 2.5-4.5 g / 10 min (MFR190℃, 2160 g), purchased from Xinjiang Lanshan Tunhe Technology Co., Ltd.) were mixed in a mass ratio of 1:1 and electrospun to prepare fibers with an average diameter of 1.96 μm and an area density of 36.27 g / m 2The fiber felt was then hot-pressed at 60°C and then cold-pressed to obtain a bulk density of 0.0684 g / cm 3 coating layer.

[0120] S1.2 Using the film layer as the receiving substrate, a mixed masterbatch of polyurethane and polypyrrole powder (purchased from Shanghai MacLean Biochemical Technology Co., Ltd.) as the island component and polyvinyl alcohol as the sea component were composite-spinned using a melt electrospinning direct writing device to obtain a sea-island fiber felt;

[0121] The island-in-the-sea fiber was prepared by the island-fixing method, with 36 islands.

[0122] The polypyrrole powder in the mixed masterbatch is 1.5% by mass and is prepared by the following method: polyurethane and polypyrrole powder are melt-blended at 180° C. using a conical twin-screw extruder, and then cooled and granulated after extrusion.

[0123] The materials were added according to a mass ratio of the second polymer in the sea component to the third polymer in the island component of 1:1.2.

[0124] The melt electrospinning apparatus was programmed to arrange the extruded island-in-the-sea fibers in a parallelogram grid. The longest diagonal of the parallelogram was 500 μm, the ratio of the longest to shortest diagonal lengths was 1.3, and the minimum angle between the longest and shortest diagonals was 80°. The spinning distance was 4 mm, the spin pack temperature was maintained at 230°C, the spinning voltage was 2 kV, and the nozzle movement speed was set at 400 mm / min.

[0125] S1.3 The sea-island fiber felt was placed in an aqueous solution and heated to 60°C for oscillation reaction for 3 hours. The wound healing medical dressing precursor was obtained after removal and drying. Microscopic observation showed that the average cross-sectional diameter of the second fiber filaments (island fibers) was 5.26 μm.

[0126] S2: Preparation of gel scaffold complex

[0127] S2.1: polyvinyl alcohol, sodium polyacrylate, and chitosan are mixed in a mass ratio of 2:10:2 to obtain a polymer, and the polymer is dissolved in ultrapure water to obtain a casting solution having a polymer content of 40%;

[0128] S2.2 Place the scaffold at the bottom of the mold, pour the casting liquid, freeze-dry to form a film, and then perform radiation cross-linking to obtain a gel scaffold complex; control the amount of casting liquid added so that the mass ratio of the gel scaffold complex to the scaffold is (0.4±0.05):1; the dose of radiation cross-linking is 60kGy, using electron accelerator β electrons; the freeze-drying conditions are as follows: freeze-dry for 24 hours at a temperature of -80°C and a vacuum of 1Pa.

[0129] S3: Preparation of wound healing medical dressings

[0130] Human epidermal keratinocytes (purchased from Hefei Wanwu Biotechnology Co., Ltd.) were seeded on the gel scaffold complex after UV disinfection and sterilization at a seeding density of 10 6 pieces / cm 2 , cultured in a 36°C, 5% carbon dioxide incubator for 8 days, with the culture medium replaced once a day; then freeze-dried to obtain a wound healing-promoting medical dressing;

[0131] The freeze-drying conditions are as follows: pre-cooling at -30°C for 2 hours, then sublimation drying at -10°C under a vacuum degree of 10 Pa for 5 hours; and sublimation drying and heat preservation at 0°C for 12 hours.

[0132] Example 4

[0133] The difference from Example 1 is that the number of islands in step S1.2 is set to 6, and the average diameter of the obtained second fiber filaments is 8.34 μm.

[0134] Example 5

[0135] The difference from Example 1 is that the number of islands in step S1.2 is set to 36, and the average diameter of the obtained second fiber filaments is 8.11 μm.

[0136] Example 6

[0137] The difference from Example 1 is that in step S1.2, the second polymer in the sea component and the third polymer in the island component are added in a mass ratio of 1:1.2, and the average diameter of the obtained second fiber filaments is 5.07 μm.

[0138] Example 7

[0139] The difference from Example 1 is that in step S1.2, the second polymer in the sea component and the third polymer in the island component are added at a mass ratio of 1:1.65, and the average diameter of the obtained second fiber filaments is 11.82 μm.

[0140] Example 8

[0141] The difference from Example 1 is that step S3 is as follows:

[0142] Stem cells were seeded in culture dishes of the same area at a density of 10 4 pieces / cm 2, cultured in a 36°C, 5% carbon dioxide incubator for 10 days, with the culture medium replaced once a day; the cells were digested with trypsin, dispersed in 1×PBS after centrifugation and freeze-dried 1, and the resulting powder was redissolved in 1×PBS to obtain an active substance solution; the gel scaffold complex was placed at the bottom of a mold, and the active substance solution was added, allowed to stand for 24 hours, and then freeze-dried 2 to obtain a wound healing-promoting medical dressing.

[0143] The mass percentage of the powder in the active substance solution is 50%. The active substance solution is dripped onto the gel scaffold complex having the same area as the culture dish.

[0144] The conditions for freeze drying 1 and freeze drying 2 were as follows: precooling at -30°C for 2 h, followed by sublimation drying at -10°C under a vacuum of 10 Pa for 5 h; and sublimation drying at 0°C with insulation for 12 h.

[0145] Example 9

[0146] The difference from Example 1 is that the conductive agent is added to the casting solution instead of the island component; the preparation method is as follows:

[0147] A method for preparing a wound healing-promoting medical dressing comprises the following steps:

[0148] S1: Preparation of scaffolds

[0149] S1.1 Melt spinning of polycaprolactone produced fibers with an average diameter of 1.65 μm and an area density of 41.22 g / m 2 The fiber felt was then hot-pressed at 60°C and then cold-pressed to obtain a bulk density of 0.094 g / cm 3 coating layer.

[0150] S1.2 Using the coating layer as a receiving substrate, polycaprolactone masterbatch as an island component and polymethylpyrrolidone as a sea component, a melt electrospinning direct writing device is used for composite spinning to obtain a sea-island fiber felt;

[0151] The island-in-the-sea fiber was prepared by the island-fixing method, with 16 islands.

[0152] The materials were added according to a mass ratio of the second polymer in the sea component to the third polymer in the island component of 1:1.4.

[0153] The melt electrospinning apparatus was programmed to arrange the extruded island-in-the-sea fibers in a parallelogram grid. The longest diagonal of the parallelogram was 500 μm, the ratio of the longest to shortest diagonal lengths was 1.3, and the minimum angle between the longest and shortest diagonals was 80°. The spinning distance was 4 mm, the spin pack temperature was maintained at 230°C, the spinning voltage was 2 kV, and the nozzle movement speed was set at 400 mm / min.

[0154] S1.3 The sea-island fiber felt was placed in an aqueous solution and heated to 60°C for oscillation reaction for 3 hours. The wound healing medical dressing precursor was obtained after removal and drying. Microscopic observation showed that the average cross-sectional diameter of the second fiber filaments (island fibers) was 8.25 μm.

[0155] S2: Preparation of gel scaffold complex

[0156] S2.1 Collagen, sodium alginate, and hydroxyethyl cellulose are mixed in a mass ratio of 10:4:2 to obtain a polymer, the polymer and glutaraldehyde are dissolved in ultrapure water in a mass ratio of 1:0.02, and nanosilver particles are added at a mass ratio of 1% by mass of the polymer to form a casting solution having a polymer content of 8%, and citric acid is added to adjust the pH of the casting solution to 6.4;

[0157] S2.2 Place the scaffold at the bottom of the mold, pour the casting liquid, heat to 75°C and let it stand for 6 hours to solidify, then freeze-dry to obtain a gel scaffold complex; control the amount of casting liquid added so that the mass ratio of the gel scaffold complex to the scaffold is (0.4±0.05):1; the freeze-drying conditions are as follows: freeze-dry for 24 hours at a temperature of -80°C and a vacuum degree of 1Pa.

[0158] S3: Same as Example 1.

[0159] Example 10

[0160] The difference from Example 1 is that the conductive agent nanosilver is not added to the island component.

[0161] Comparative Example 1

[0162] A method for preparing a wound healing-promoting medical dressing comprises the following steps:

[0163] S1: Preparation of scaffolds

[0164] S1.1 is the same as Example 1;

[0165] The difference between S1.2 and Example 1 is that the same melt electrospinning direct writing device is used, but the number of islands is set to 0, and single fibers with an average diameter of 8.32 μm are deposited on the coating layer and stacked layer by layer to 16 layers to obtain a composite fiber felt; the fiber raw material is the island component of Example 1.

[0166] S2~S3 are the same as in Example 1.

[0167] Comparative Example 2

[0168] A method for preparing a wound healing-promoting medical dressing comprises the following steps:

[0169] S1: Preparation of scaffolds

[0170] S1.1 is the same as Example 1;

[0171] S1.2 differs from Example 1 in that the same melt electrospinning direct writing device is used, but the number of islands is set to 0, and single fibers with an average diameter of 132.48 μm are deposited on the coating layer to obtain a composite fiber felt; the fiber raw material is the island component of Example 1.

[0172] S2~S3 are the same as in Example 1.

[0173] Comparative Example 3

[0174] A medical dressing does not contain an active substance. The preparation method is different from that of Example 1 in that step S3 is omitted.

[0175] The samples prepared in the above examples and comparative examples were tested using the following methods:

[0176] (1) Stent porosity test

[0177] The porosity was determined by the solvent filling method, as follows: a dried scaffold with a mass of m1 was immersed in a container filled with anhydrous ethanol, and the vacuum was circulated until no bubbles escaped. The total weight of the scaffold, scaffold, and container was weighed as m2. The scaffold after the liquid was absorbed was removed, and the total weight of the container and the remaining anhydrous ethanol was weighed as m3. The porosity was calculated according to the following formula I. The test was repeated three times in parallel and the average value was taken.

[0178] Porosity = (m2-m3-m1) / (m2-m3)×100% Formula I

[0179] (2) Stent pore size and pore size distribution test

[0180] The pore size and pore size distribution of the stent were measured using the bubble pressure method using a fully automatic thin film pore size measuring instrument from the United States. The pore size distribution range and the ratio of the sum of the pore volumes of pores with a pore size of less than or equal to 8 μm to the sum of the pore volumes of pores with a pore size of less than or equal to 15 μm were obtained.

[0181] The porosity and pore size, i.e., pore size distribution, measured in Examples 1 to 7 and Comparative Examples 1 to 2 are shown in Table 1.

[0182] Table 1

[0183]

[0184] As can be seen from Table 1, the scaffold of the wound-healing medical dressing provided by the present invention has a high porosity. While meeting the mechanical properties, it can support and absorb more gel, thereby providing a larger pore structure to load active substances. In addition, the pore size range of the scaffold is 2 to 15 μm, and the ratio of the sum of the pore volumes of pores with a pore size of 8 μm or less to the sum of the pore volumes of pores with a pore size of 15 μm or less is greater than 80%. Because when the porosity is similar, the greater the proportion of small-diameter pores and the smaller the large-diameter pores of the wound-healing medical dressing, the better the sealing ability. A pore size that is too large can lead to the penetration of foreign contaminants and the leakage of contents.

[0185] The fiber bundles of the support layers of Examples 1, 4, and 5 have different numbers of second fiber filaments. As the number of second fiber filaments increases, the porosity becomes smaller. The reason is that as the number of second fiber filaments increases, the volume density of the scaffold increases, and thus the porosity decreases; however, the second fiber filaments will divide the pores formed by the first fiber filaments, thereby increasing the number of small pores. The second fiber filaments of the support layer of Examples 1, 6, and 7 have different diameters. As the diameter increases, the porosity decreases, but The larger the diameter, the greater the second fiber filaments covered on the surface of the coating layer, the greater the degree of segmentation of the pores formed by the first fiber filaments, but at the same time the volume density of the scaffold is increased, resulting in a decrease in porosity. Comparative Example 1: The mesh structure prepared by stacking single fiber filaments layer by layer during the melt electrospinning direct writing process has a porosity and The reason is that the fiber filaments are difficult to align accurately in this way, resulting in the distance between the fiber filaments gradually deviating and becoming smaller, so the degree of segmentation of the pores formed by the first fiber filaments is greater. In addition, because the fiber filaments of the support layer are stacked relatively loosely in this way, it is beneficial to increase the porosity. The support layer of Comparative Example 2 is composed of a single fiber with a diameter equivalent to that of Example 1 to form a mesh frame, and the degree of segmentation of the pores formed by the first fiber filaments is smaller, so Smaller than Example 2.

[0186] (3) Bracket surface density and volume density test

[0187] Cut the bracket and prepare a 3cm×3cm square sample. Use a precision balance to weigh the mass of the sample and calculate the surface density of the bracket. Then use a spiral micrometer to measure the thickness of the fiber membrane and calculate the volume density. Randomly measure the same sample 10 times and take the average value.

[0188] (4) Mechanical properties test of the stent

[0189] ① Breaking strength and elongation at break

[0190] Testing was performed using a tensile testing machine. The stent was cut into strips measuring 80 mm x 20 mm in length x width. The test was repeated three times at a tensile speed of 5 mm / min, and the average value was taken. The breaking strength refers to the strength of the strip sample at break, calculated by multiplying the tensile force at break and the cross-sectional area of the strip sample. The breaking elongation refers to the elongation of the strip sample at break, calculated by multiplying the displacement at break and the length of the strip sample. The longitudinal-to-transverse stiffness ratio refers to the ratio of the sample's longitudinal Young's modulus to its transverse Young's modulus, where the longitudinal direction refers to the direction of the longest diagonal of the parallelogram of the support layer in the stent, and the transverse direction refers to the direction perpendicular to the longitudinal direction.

[0191] ② Cycle performance

[0192] Stretch the strip sample according to method ① to a stretch of 20%, record the fixture displacement as L1, then restore the fixture to a displacement of 0 at the same speed, and immediately move to L1 at the same speed. After 100 cycles, let it stand for 10 minutes, and then test the breaking strength and elongation at break according to method ①.

[0193] The mechanical property test results of Examples 1 to 7 and Comparative Examples 1 to 2 are shown in Table 2.

[0194] Table 2

[0195]

[0196]

[0197] As can be seen from Table 2, the stent obtained in the embodiment of the present invention has better mechanical properties and cycle performance than the comparative example. Comparative Example 1 is a mesh structure prepared by stacking single fiber filaments layer by layer in the process of melt electrospinning direct writing. Since the fiber filaments of each layer are difficult to align accurately, it is difficult for the fiber filaments to form strands and play a role in reinforcing each other, so the strength is low and the cycle performance is poor; in addition, since the fiber filaments of the layer are difficult to align accurately, the shape is deformed, so the longitudinal and transverse stiffness ratio is reduced, that is, the anisotropy decreases. Comparative Example 2 is a mesh frame composed of a single fiber filament with a thicker diameter. Due to the poor mobility of the fiber filament, the elongation at break is low, the elasticity is poor, and the cycle performance is poor. The reason is that the stress of the single fiber filament is difficult to dissipate quickly during the cycle, resulting in accumulation, and the fatigue resistance is poor. The fiber bundles of the support layers of Examples 1, 4, and 5 have different numbers of second fiber filaments. With the increase of the second fiber filaments, the breaking strength, elongation at break, and longitudinal and transverse stiffness ratio all increase, and the cycle performance is improved. The second fiber filaments of the support layer of Examples 1, 6, and 7 have different diameters. As the diameter increases, the breaking strength, elongation at break, and longitudinal-to-transverse stiffness ratio all increase, but the cyclic performance first increases and then decreases. This is because an excessively large diameter of the second fiber filament leads to poor fatigue resistance, resulting in a decrease in cyclic performance. In addition, the longitudinal and transverse stiffness of the stent should be maintained within a reasonable range to conform to the anisotropic stiffness ratio of the muscles in the application area. The ratio of the longitudinal to transverse strength of human skin is approximately 1.5 to 3, and this can be regulated by controlling the diameter and number of the second fiber filaments to adapt to different application scenarios.

[0198] (5) Dressing conductivity test

[0199] The resistance of the wet dressing was tested using a dual-probe benchtop digital multimeter. Five measurements were taken longitudinally and transversely, and the average value was taken. The conductivity was calculated (conductivity = 1 / resistivity = electrode spacing ÷ resistance ÷ cross-sectional area). The wet dressing was prepared by gradually adding 1× PBS solution dropwise to the skin-contacting surface of the dressing (the surface of the original support layer). When the incremental mass of the wet dressing reached 20% and 40% of the dry dressing, the addition was stopped and the dressing was allowed to stand for 1 hour to obtain the wet dressing to be tested.

[0200] The electrical conductivities of Examples 1, 4, 5, 9, 10 and Comparative Example 2 are listed in Table 3.

[0201] Table 3

[0202]

[0203] As shown in Table 3, the stents of Examples 1, 4, and 5 contain second fibers of similar diameters but in varying numbers. As the number increases, the resistance decreases and the conductivity increases. In Example 9, a conductive agent is added to the casting solution, so it is present in the gel of the dressing. Because the gel has a greater ability to absorb and swell than the second fibers, the difference in mass increments between 20% and 40% is significant. This means that the conductivity stability of Example 9 is inferior to that of Example 1. Conductivity stability is crucial for exogenous electrical stimulation therapy; higher conductivity stability indicates better safety.

[0204] (6) Wound healing test

[0205] A mouse wound model was used to evaluate the wound healing performance of the dressing. SPF-grade male Wistar rats (weight range, 200-250 g) were provided by the Experimental Animal Center of Southern Medical University. The rats were untreated before surgery and were fed adaptively for 3 days before the experiment began. They had free access to water and food during the experiment. The rats were anesthetically injected intraperitoneally (10% chloral hydrate, 400 mg / kg), and their dorsal hair was shaved with an electric shaver. Two symmetrical dorsal wounds were created by resecting full-thickness skin with a diameter of 18 mm on both sides of the rat's back, reaching the fascia layer. After wound disinfection, the same test dressing was applied to the left and right wounds, respectively. One of the wounds with the test dressing was treated with electrical stimulation every two days for 15 minutes. The dressing was changed every three days (on the 4th, 7th, 9th, and 11th days, respectively), and the wound diameter was measured. Five mice were tested for each test dressing, and the average value was taken. The results are listed in Table 4.

[0206] Table 4

[0207]

[0208]

[0209] As can be seen from the data in Table 4, the healing rate of electrically stimulated wounds in all experimental mice was greater than that of static wounds, indicating that combined in vitro electrical stimulation therapy can promote wound healing. Although no conductive agent was added to Example 10, the other materials of the dressing and water all had a certain degree of conductivity, so the effect of electrical stimulation on promoting healing was also exerted, but the therapeutic effect was not as good as other specific embodiments. Comparative Example 3 did not add active substances to Example 1, and the healing rates of its electrically stimulated wounds and static wounds were both lower than those of Example 1. Compared with Example 1, Example 8 was mixed with the gel scaffold complex after culturing and extraction in a different place. Since the active substance underwent two freeze-dryings and a series of separation operations, its activity and content were lower than the active substance loaded on the dressing in Example 1. Therefore, it can be seen that the healing rate of the static wound under Example 1 is higher than that of Example 8. It can be seen that the in situ growth of the active substance is conducive to improving the bioavailability and improving the healing effect of the active substance. Example 9 added a conductive agent to the casting solution, so the conductive agent was present in the gel of the dressing. The healing rate of its electrically stimulated wound was lower than that of Example 1, indicating that the stability of conductivity is conducive to achieving the therapeutic effect of electrical stimulation therapy.

[0210] Example 11

[0211] This embodiment provides a melt electrospinning direct writing device, the structure of which is shown in FIG. Figure 2 , comprising: an upper cover plate (1) and a lower cover plate (2), a fiber microscope camera (3) connected to the lower end of the upper cover plate (1) through a rotating shaft, a melt insulation chamber (4) fixed to the lower end of the upper cover plate (1) and a spinning assembly (5) provided at the bottom; an X-direction guide rail (61) and a Y-direction guide rail (62) are provided at the upper end of the lower cover plate (2), and a Z-direction guide rail (63) is provided at the lower end of the lower cover plate (2), wherein the Z-direction guide rail (63) passes through the lower cover plate (2) to adjust the displacement of the X-direction guide rail (61) and the Y-direction guide rail (62) in the Z-axis direction; a jet microscope camera bracket (7) and a receiving plate bracket (8) are respectively fixed on the X-direction guide rail (61), and the jet microscope The camera (71) and the receiving plate (81) are respectively fixed to the upper ends of the jet micro-camera bracket (7) and the receiving plate bracket (8), so that the jet micro-camera (71) can observe the state of the melt jet reaching a certain range near the surface of the receiving plate (81); the jet micro-camera (71) and the fiber micro-camera (3) are connected to the computer (9) through the control element for displaying the motion state of the melt jet and the morphology and position of the fiber; a voltage is connected between the spinning assembly (5) and the receiving plate (81) to form a high-voltage electrostatic field between the spinning needle end and the receiving plate end; the upper cover plate (1) and the lower cover plate (2) are separated by a plurality of columnar bodies or plate-shaped bodies to form a cavity.

[0212] Wherein, the receiving plate (81) is an ITO conductive glass plate.

[0213] The local structure of the melt insulation chamber (4) is shown in the attached Figure 3 ,like Figure 3 As shown, a barrel 1 (411) and a barrel 2 (412) are provided in the melt insulation chamber (4), and an electromagnetic heating coil 1 (421) and an electromagnetic heating coil 2 (422) are respectively sleeved on the outer walls of the barrel 1 (411) and the barrel 2 (412) to heat and insulate them. The upper ends of the barrel 1 (411) and the barrel 2 (412) are respectively provided with openings and pass through the upper cover plate (1). The double-channel air compressor (10) is connected to the upper end openings of the barrel 1 (411) and the barrel 2 (412) through a conduit. The extrusion rate of the melt is adjusted by controlling the air pressure applied by the double-channel air compressor (10), thereby controlling the proportion of each component; the lower ends of the barrel 1 (411) and the barrel 2 (412) are respectively provided with openings and are connected to the spinning assembly (5) through a conduit. For example, barrel 1 (411) and barrel 2 (412) are respectively used to place the melt of the sea component and the melt of the island component. Different air pressures are applied by a dual-channel air compressor (10) to control the flow rate of the sea component melt and the melt of the island component, thereby controlling the mass ratio of the sea component and the island component in the sea island fiber. By adding the masterbatch into the barrel and heating the barrel with an electromagnetic heating coil to melt it into a melt, when the island component includes more than two materials, all the raw materials need to be mixed and granulated before being put into the barrel for melting.

[0214] The local structure of the spinning assembly (5) is shown in the attached Figure 4 ,like Figure 4 As shown, the spinning assembly (5) includes a blanking plate (51), a distribution plate (52), a needle plate (53), a pinhole plate (54) and a spinneret (55), and the blanking plate (51), the distribution plate (52), the needle plate (53), the pinhole plate (54) and the spinneret (55) are connected by at least one bolt passing through them.

[0215] The blanking plate (51) is provided with an island component feed hole (511) and a sea component feed hole (512) penetrating the blanking plate (51), and the island component feed hole (511) and the sea component feed hole (512) are respectively connected to the lower ends of the barrel 1 (411) and the barrel 2 (412) through conduits;

[0216] The distribution plate (52) is provided with an island component branch channel (521) and a sea component branch channel (522); the sea component branch channel (522) is communicated with the sea component feed hole (512) and is used to receive the sea component input from the sea component feed hole (512) and divide it into multiple channels for discharge; the island component branch channel (521) passes through the distribution plate (52) and is communicated with the island component feed hole (511) and is used to receive the island component input from the island component feed hole (511).

[0217] The needle plate (53) includes an island component receiving hole (531), a sea component flow channel (532), and a needle tube group (533); the island component receiving hole (531) is opened on the upper surface of the needle plate (53) and is recessed therein; the needle tube group (533) (the number of needle tubes in the needle tube group is determined according to the number of islands) is formed in the needle plate (53) and is connected to the island component receiving hole (531); the island component receiving hole (531) and the island component diversion channel (521) are mutually connected and are used to receive the island component input by the island component diversion channel (521). The island component receiving hole (531) and the needle tube group (533) are arranged above and below each other, so that the island component received by the island component receiving hole (531) is distributed through multiple needle tubes (5331).

[0218] The sea component flow channel (532) comprises a plurality of receiving holes (5321) provided on the upper surface of the needle plate (53) and recessed therein, a groove portion (5323) provided on the lower surface of the needle plate (53) and recessed therein, and a plurality of material guide holes (5322) between the receiving holes (5321) and the groove portion (5323), each receiving hole (5321) being in one-to-one communication with each sea component flow channel (522), and each material guide hole (5322) being in one-to-one communication with each receiving hole (5321);

[0219] The pinhole plate (54) is provided with an island hole (541) and a side hole (542) penetrating the pinhole plate (54). A plurality of island holes (541) are provided and correspond to each needle tube (5331) one by one. A plurality of side holes (542) are provided and are arranged around the periphery of the plurality of island holes (541). The diameter of the upper end of the island hole (541) is slightly larger than the diameter of the needle tube (5331), so that the island hole (541) is connected to the sea component guide channel (532). At the same time, the sea component guide channel The diameter of the flow channel (532) is relatively large, and it also extends to connect with the side hole (542) (that is, the island hole (541) and the side hole (542) are also respectively connected with the groove portion of the sea component flow guide channel (532)). In this way, the island component flows directly into the island hole (541) through the needle tube (5331), and at the same time, the sea component also flows into the island hole (541) to achieve confluence and form a skin-core type polymer; at the same time, the sea component also flows downward through the side hole (542).

[0220] The spinneret (55) is provided with a spinneret hole (551) which passes through the spinneret (55) and is connected to the island hole (541) and the side hole (542). The spinneret hole (551) has a cone portion and a discharge hole portion located below the cone portion and connected to the cone portion, so that the core-sheath polymer above and the sea component flowing down through the side hole (542) merge, thereby continuing to cover the surface of the core-sheath polymer with the sea component to form an outer layer, and finally forming a combined island fiber.

[0221] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A wound healing-promoting medical dressing, characterized in that: It comprises a scaffold, a gel and an active ingredient; the scaffold comprises a coating layer in which first fiber filaments are arranged in a disordered manner and a supporting layer in which fiber bundles are arranged in a parallelogram grid structure; the fiber bundles are composed of at least 6 separate second fiber filaments; and the active ingredient comprises a growth factor.

2. The wound healing-promoting medical dressing according to claim 1, characterized in that: The wound healing promoting medical dressing satisfies at least one of the following characteristics 1 to 3: Feature 1: The longitudinal to transverse stiffness ratio of the stent is 1.5 to 3, wherein the longitudinal to transverse stiffness ratio refers to the ratio of the Young's modulus of the stent in the longitudinal and transverse directions; Feature 2: The second fiber filament includes a conductive agent; preferably, the conductive agent is selected from at least one of silver, polypyrrole, graphene, carbon nanotubes and carbon nanowires; Feature 3: The gel is made of one or more of the following materials: polyvinyl alcohol or its derivatives, polyacrylic acid or its derivatives, collagen or its derivatives, gelatin or its derivatives, hyaluronic acid or its derivatives, alginate or its derivatives, chitosan or its derivatives, cellulose derivatives, carbomer, polyethylene oxide.

3. The wound healing-promoting medical dressing according to any one of claims 1 to 2, characterized in that: The wound healing promoting medical dressing satisfies at least one of the following characteristics i to iii Feature i: The porosity of the scaffold is 60% to 80%; Feature ii: The pore size of the scaffold is in the range of 2 to 15 μm; and the ratio of the sum of the pore volumes of pores with a pore size of 8 μm or less to the sum of the pore volumes of pores with a pore size of 15 μm or less is 80% or more; Feature iii: The growth factors include at least one of epidermal growth factor EGF, vascular endothelial growth factor VEGF, basic fibroblast growth factor bFGF, transforming growth factor-β1TGF-β1, transforming growth factor-β2TGF-β2, transforming growth factor-β3TGF-β3, insulin-like growth factor IGF-1 and insulin-like growth factor II IGF-2.

4. The wound healing-promoting medical dressing according to any one of claims 1 to 3, characterized in that: The active ingredient comes from the extracellular matrix, and the extracellular matrix comes from at least one of human fibroblasts, bone marrow mesenchymal stem cells, adipose mesenchymal stem cells and skin keratinocytes.

5. The wound healing promoting medical dressing according to any one of claims 1 to 4, characterized in that: The bracket satisfies at least one of the following characteristics 1 to 7: Feature 1: The average cross-sectional diameter of the first fiber is 1 to 2 μm; Feature 2: The first fiber filament comprises at least one of polyester, polylactic acid, polyglycolic acid, and polyurethane; wherein the polyester comprises at least one of polycaprolactone, polyglycerol sebacate, polybutylene adipate / terephthalate, polybutylene succinate terephthalate, β-hydroxybutyric acid and β-hydroxyvalerate copolymer, and lactide / caprolactone copolymer; Feature 3: The fiber bundle includes 6 to 36 individual second fiber filaments; Feature 4: The average cross-sectional diameter of the second fiber is 5 to 12 μm; Feature 5: The second fiber filament comprises at least one of the following polymers: polyester, polylactic acid, polyglycolic acid, and polyurethane; the polyester comprises at least one of polycaprolactone, polyglycerol sebacate, polybutylene adipate / terephthalate, polybutylene succinate terephthalate, β-hydroxybutyric acid and β-hydroxyvalerate copolymer, and lactide / caprolactone copolymer; Feature 6: The longest diagonal of the parallelogram is 400-600 μm, the ratio of the length of the longest diagonal to the shortest diagonal is 1.2-1.4, and the minimum angle between the longest diagonal and the shortest diagonal is 45-90°; Feature 7: The volume density of the coating layer is 0.06-0.15 g / cm 3 .

6. The method for preparing the wound healing-promoting medical dressing according to any one of claims 1 to 5, characterized in that: The following steps are involved: S1: Preparation of scaffolds S1.1 spinning the first polymer 1 and pressing it to prepare a coating layer; S1.2 Using the coating layer as a receiving substrate, spinning the sea component and the island component by melt electrospinning according to a set program to obtain a sea-island fiber felt in which the sea-island fibers are arranged in a parallelogram structure; S1.3 reducing the sea-island fiber felt and drying it to obtain a bracket; S2: Preparation of gel scaffold complex The scaffold is placed at the bottom of the mold, a casting solution is poured, solidified and freeze-dried to obtain a gel-scaffold complex; S3: Preparation of wound healing medical dressings The living cells are inoculated onto the gel scaffold complex for culture, and then subjected to a second freeze-drying process to obtain a wound healing-promoting medical dressing.

7. The preparation method according to claim 6, characterized in that The preparation method satisfies at least one of the following characteristics I to IV: Feature I: The first polymer comprises at least one of polyester, polylactic acid, and polyurethane, wherein the polyester comprises at least one of polycaprolactone, polyglycerol sebacate, and lactide / caprolactone copolymer; Feature II: The sea component includes a second polymer, and the second polymer includes at least one of polyvinyl alcohol and polymethylpyrrolidone; Feature III: The island component includes a third polymer; the third polymer includes at least one of polyester, polylactic acid, and polyurethane; wherein the polyester includes at least one of polycaprolactone, polyglycerol sebacate, polyhydroxybutyrate, and lactide / caprolactone copolymer; Feature IV: The island component includes a third polymer and a conductive agent; the third polymer includes at least one of polyester, polylactic acid and polyurethane; wherein the polyester includes at least one of polycaprolactone, polyglycerol sebacate, polyhydroxybutyrate and lactide / caprolactone copolymer; the conductive agent includes at least one of silver, polypyrrole, graphene, carbon nanotubes and carbon nanowires.

8. The preparation method according to claim 7, characterized in that The preparation method satisfies at least one of the following characteristics V to XI: Feature V: The mass ratio of the second polymer to the third polymer is 1:1.2-1.6; Feature VI: The number of islands in the sea-island fiber is 6 to 36; Feature VII: The conductive agent accounts for 0.5% to 1.5% by mass of the island component; Feature VIII: The spinning 1 is solution spinning or melt spinning; Feature IX: The pressing comprises pressing the fiber felt obtained by spinning 1 into a coating layer with a target bulk density of 0.06 to 0.15 g / cm 3 ; Feature X: The melt electrospinning writing (MEW) method comprises: flowing a molten polymer through a nozzle to form a melt stream, which is stretched under the action of an electrostatic field and guided onto a movable receiver to form a desired fiber structure; Feature XI: The reduction refers to removing the second polymer in water.

9. The preparation method according to any one of claims 6 to 8, characterized in that The casting solution comprises a high molecular polymer; the high molecular polymer is selected from one or more of polyvinyl alcohol or its derivatives, polyacrylic acid or its derivatives, collagen or its derivatives, gelatin or its derivatives, hyaluronic acid or its derivatives, alginate or its derivatives, chitosan or its derivatives, cellulose derivatives, carbomer and polyethylene oxide; And / or, the casting solution comprises a polymer and a cross-linking agent; the casting solution comprises a polymer; the polymer is selected from one or more of polyvinyl alcohol or its derivatives, polyacrylic acid or its derivatives, collagen or its derivatives, gelatin or its derivatives, hyaluronic acid or its derivatives, alginate or its derivatives, chitosan or its derivatives, cellulose derivatives, carbomer and polyethylene oxide; the cross-linking agent is selected from at least one of glutaraldehyde, genipin, hexanediol diglycidyl ether, calcium salt, transglutaminase, laccase and peroxidase; And / or, the curing refers to static crosslinking or radiation crosslinking at 25-80°C.

10. A melt electrospinning direct writing device, characterized in that: include: An upper cover plate and a lower cover plate, a fiber microscope camera is connected to the lower end of the upper cover plate, a melt holding chamber is fixed to the lower end of the upper cover plate, and a spinning assembly is provided at the bottom; an X-direction guide rail and a Y-direction guide rail are provided at the upper end of the lower cover plate, and a Z-direction guide rail is provided at the lower end of the lower cover plate and passes through the lower cover plate; a jet microscope camera bracket and a receiving plate bracket are respectively fixed to the X-direction guide rail, and a jet microscope camera and a receiving plate are respectively fixed to the upper ends of the jet microscope camera bracket and the receiving plate bracket; the jet microscope camera and the fiber microscope camera are connected to a computer via a control element; a voltage is connected between the spinning assembly and the receiving plate to form a high-voltage electrostatic field; The melt insulation chamber is provided with a barrel 1 and a barrel 2, and the outer walls of the barrel 1 and the barrel 2 are respectively provided with an electromagnetic heating coil 1 and an electromagnetic heating coil 2. The upper ends of the barrel 1 and the barrel 2 are respectively provided with openings and pass through the upper cover plate. The double-channel air compressor is connected to the upper end openings of the barrel 1 and the barrel 2 respectively through a conduit; the lower ends of the barrel 1 and the barrel 2 are respectively provided with openings and connected to the spinning assembly through a conduit; The spinning assembly includes a blanking plate, a distribution plate, a needle plate, a pinhole plate and a spinneret; the blanking plate is provided with an island component feed hole and a sea component feed hole penetrating the blanking plate; the distribution plate is provided with an island component flow channel and a sea component flow channel; The needle plate includes an island component receiving hole, a sea component flow guide and a needle tube group; the island component receiving hole is opened on the upper surface of the needle plate and is recessed therein; the needle tube group is formed in the needle plate so as to be connected with the island component receiving hole; the island component receiving hole and the needle tube group are arranged above and below each other, and the needle tube group includes a plurality of needle tubes; the sea component flow guide includes a plurality of receiving holes provided on the upper surface of the needle plate and recessed therein, a groove portion on the lower surface of the needle plate and recessed therein, and a plurality of material guide holes between the receiving holes and the groove portion; The pinhole plate is provided with island holes and side holes penetrating the pinhole plate, the island holes corresponding to each needle tube one by one, and the side holes are arranged around the island holes; the upper end diameter of the island holes is larger than the diameter of the needle tube; and the groove portion extends to communicate with the side holes; The spinneret is provided with a spinneret hole which penetrates the spinneret and is connected with the island hole and the side hole. The spinneret hole has a cone portion and a discharge hole portion which is located below the cone portion and is connected with the cone portion.

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