Composition for forming bionic dressing, bionic dressing and method for forming bionic dressing

Abstract

Provided herein are biomimetic dressing forming compositions, biomimetic dressings, and methods of forming biomimetic dressings. The biomimetic dressing forming composition provided herein comprises an aqueous phase and an oil phase, in which the oil phase comprises a hydrophobic prepolymer or a hydrophobic monomer having a first photopolymerizable functional group, the oil phase having an intrinsic viscosity of less than 106 mPa.s at room temperature; the water phase contains a hydrophilic hydrogel prepolymer or a hydrophilic hydrogel monomer and an active component, the hydrophilic hydrogel prepolymer or the hydrophilic hydrogel monomer has a second photopolymerization functional group, and the water phase has intrinsic viscosity lower than 106 mPa.s at normal temperature; the first photopolymerizable functional group and the second photopolymerizable functional group comprise-C = C-bonds and can be polymerized and / or cross-linked by photoinitiation, and after the composition is applied, the oil phase and the water phase can be self-layered and form a bionic dressing having a bilayer cross-linked structure of a hydrophobic polymer and a hydrophilic hydrogel.

Description

Technical Field

[0001] The present disclosure generally relates to biomimetic dressing-forming compositions, biomimetic dressings, and methods of forming biomimetic dressings. Background Art

[0002] The skin is an elastic and multi-layered tissue. It is also the largest organ in the human body and has the function of sensing and protecting the body from physical damage and pathogen invasion. Large-area trauma accompanied by acute and uncontrollable bleeding can pose a real threat to survival. Although wound dressings have made great progress today, inappropriate dressing selection and wound management are still prone to infection, difficult to heal, and even lead to scar formation, which brings a huge burden to both patients and health systems. Clinically, various dressings have been widely used in wound management. Among all dressings, hydrogel products such as PIVOT (alginate) and Simpurity TM Polyvinyl alcohol (PVA) is considered to be a better choice than other materials (such as cotton sponge, rubber and foam) due to its outstanding advantages of maintaining a moist repair environment, absorbing tissue exudate and simulating the extracellular matrix (ECM).

[0003] However, the hydrogel dressings currently available on the market generally lack rapid hemostatic properties and cannot be used for large-area emergency wounds accompanied by uncontrollable bleeding. In addition, current hydrogel dressings also exhibit limited wound adhesion and mechanical properties that resist external interference. They also suffer from problems such as excessive water evaporation and inevitable microbial infection, which lead to delayed wound healing. In addition, scar-free repair has always been one of the goals pursued by the medical community, and current hydrogel dressings may cause obvious scar formation, affecting the patient's appearance and quality of life. In summary, current hydrogel dressings lack sufficient protection, cleaning and nourishment for the wound site, so there is a need for a new dressing that can accelerate wound hemostasis and healing while inhibiting scar hyperplasia. Summary of the Invention

[0004] One of the purposes of the present invention is to provide a novel bionic dressing forming composition, which can conveniently form a bionic dressing to achieve rapid hemostasis of wounds, while providing a moist and sterile environment, which is conducive to scarless healing of wounds.

[0005] In a first aspect, the present invention provides a biomimetic dressing forming composition comprising an aqueous phase and an oil phase, wherein

[0006] The oil phase contains a hydrophobic prepolymer or a hydrophobic monomer, wherein the hydrophobic prepolymer or the hydrophobic monomer has a first photopolymerizable functional group, and the oil phase has a hydrophobicity of less than 10 at room temperature. 6an intrinsic viscosity of mPa·s, for example, an intrinsic viscosity of 1-1000 mPa·s, 10-200 mPa·s, 5-100 mPa·s, or 1-80 mPa·s;

[0007] The aqueous phase contains a hydrophilic hydrogel prepolymer or a hydrophilic hydrogel monomer and an active ingredient, wherein the hydrophilic hydrogel prepolymer or the hydrophilic hydrogel monomer has a second photopolymerizable functional group, and the aqueous phase has a photocatalytic activity of less than 10 6 an intrinsic viscosity of mPa·s, for example, an intrinsic viscosity of 1-1000 mPa·s, 20-200 mPa·s, 10-100 mPa·s, 5-50 mPa·s, or 1-30 mPa·s;

[0008] The first photopolymerizable functional group and the second photopolymerizable functional group contain a -C=C- bond and are capable of polymerization and / or crosslinking initiated by light, and

[0009] After application of the composition, the oil phase and the water phase can self-separate and form a biomimetic dressing having a double-layer cross-linked structure of a hydrophobic polymer and a hydrophilic hydrogel.

[0010] In certain embodiments, the first photopolymerizable functional group and the second photopolymerizable functional group in the biomimetic dressing-forming composition of the present invention include one or more of acrylate, methacrylate, acrylamide, methacrylamide, styrene, N-vinyl pyrrolidone, hydroxybutyl vinyl ether, diethylene glycol divinyl ether, or phenyl glycidyl ether.

[0011] In certain embodiments, the hydrophobic prepolymer or hydrophobic monomer includes one or more of poly(lactic acid-propylene glycol-lactic acid) dimethacrylate, polypropylene glycol diacrylate, polypropylene glycol dimethacrylate, polypropylene acrylate, and polymethyl methacrylate.

[0012] In certain embodiments, the composition further comprises a first photoinitiator for initiating polymerization and / or crosslinking of the hydrophobic prepolymer or hydrophobic monomer, preferably the first photoinitiator comprises bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide or lithium phenyl-2,4,6-trimethylbenzoylphosphinate.

[0013] In certain embodiments, the hydrophilic hydrogel prepolymer or hydrophilic hydrogel monomer comprises one or more of methacrylated gelatin, acrylated gelatin, methacrylated hyaluronic acid, acrylated hyaluronic acid, methacrylated chitosan, acrylated chitosan, and hydrophilic polyethylene glycol diacrylate.

[0014] In certain embodiments, the composition further comprises a second photoinitiator for initiating polymerization and / or crosslinking of the hydrophilic hydrogel prepolymer or the hydrophilic hydrogel monomer, preferably the second photoinitiator comprises 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone or camphorquinone.

[0015] In certain embodiments, the active ingredient in the aqueous phase is selected from a hemostatic active ingredient, such as a water-soluble calcium salt (eg, CaCl2) or thrombin; a wound healing active ingredient such as a growth factor; or a combination thereof.

[0016] In certain embodiments, the concentration of the active ingredient in the aqueous phase is 0.1-70% by weight, preferably 5-30% by weight, or more preferably 5-10% by weight.

[0017] In certain embodiments, the oil phase and / or the water phase further comprises an antimicrobial active ingredient.

[0018] In certain embodiments, the antimicrobial active ingredient is selected from triclosan and curcumin.

[0019] In certain embodiments, the concentration of the antimicrobial active ingredient in the oil phase is 0.1-20% by weight, preferably 1-10% by weight, or more preferably 2-7% by weight.

[0020] In certain embodiments, the composition does not include an emulsifier or surfactant.

[0021] In certain embodiments, the composition forms a biomimetic dressing having a double-layer cross-linked structure within 100 seconds, preferably within 80 seconds, within 60 seconds, within 50 seconds, within 40 seconds, within 30 seconds, within 20 seconds, within 10 seconds, within 5 seconds or within 1 second after photoinitiation.

[0022] In certain embodiments, the composition is in the form of a liquid formulation.

[0023] In certain embodiments, the liquid formulation is in the form of a spray.

[0024] In certain embodiments, wherein the composition comprises:

[0025] an oil phase comprising poly(lactic acid-propylene glycol-lactic acid) dimethacrylate and triclosan;

[0026] Aqueous phase, which contains methacryloyl gelatin and Ca 2+ .

[0027] In a second aspect, the present invention provides a biomimetic dressing formed from the biomimetic dressing-forming composition described above. The biomimetic dressing comprises at least one bilayer structure comprising a skin-conforming layer and an outer layer, the outer layer being adjacent to the skin-conforming layer, wherein the skin-conforming layer contacts the skin and comprises a hydrophilic hydrogel, and the outer layer comprises a hydrophobic polymer. In the biomimetic dressing, the hydrophilic hydrogel is formed from an aqueous phase comprising a hydrophilic hydrogel prepolymer or a hydrophilic hydrogel monomer and an active ingredient, and the hydrophobic polymer is formed from an oil phase comprising a hydrophobic prepolymer or a hydrophobic monomer.

[0028] In certain embodiments, the biomimetic dressing of the present invention is formed by the following process:

[0029] mixing the oil phase and the aqueous phase to form a suspension comprising the oil phase and the aqueous phase,

[0030] applying the suspension to a surface to form an uncured biomimetic dressing, and

[0031] The uncured biomimetic dressing is irradiated with light to form the biomimetic dressing.

[0032] In a third aspect of the present invention, there is provided use of the biomimetic dressing-forming composition as described above in preparing a biomimetic dressing.

[0033] In a fourth aspect of the present invention, a method for forming the above-mentioned biomimetic dressing is provided, the method comprising:

[0034] applying a suspension comprising an aqueous phase and an oily phase of the biomimetic dressing-forming composition as described above; and

[0035] The suspension is cured by photo-initiated polymerization and / or cross-linking to obtain the biomimetic dressing.

[0036] The above technical solution of the present invention has at least the following advantages.

[0037] 1. The bionic dressing of the present invention has a skin-fitting layer that can fit the skin wound, which can achieve rapid hemostasis of the wound, firmly adhere to the wound site and adapt to joint movement. The outer layer of the bionic dressing can provide the strength required by the dressing and isolate the wound site from the outside world, thereby maintaining a moist and sterile environment at the wound site, which is conducive to achieving scarless healing of the wound.

[0038] 2. The biomimetic dressing of the present invention allows for the loading of multiple material components in both the skin-adhering layer and the outer layer to match the cascade process of wound healing and meet the needs of precise medical treatment for different wound conditions. For example, the skin-adhering layer may contain Ca 2+ , so that the layer can activate the coagulation cascade reaction, further facilitating rapid hemostasis; the outer layer can be loaded with triclosan (TCS) to enhance the antibacterial effect.

[0039] 3. The oil phase and the water phase of the biomimetic dressing composition provided by the present invention both contain photocrosslinking materials, so they can be rapidly polymerized and / or crosslinked in situ during application, and the interface between the two layers can have a strong interfacial force to prevent interlayer peeling.

[0040] 4. The biomimetic dressing composition of the present invention is sprayable, making it easy to apply to irregular or large wounds. This feature can quickly reduce pain and infection risk, while also offering ease of use. In particular, the in situ hydrogel-containing skin-conforming layer offers significant advantages over existing preformed hydrogels, including excellent portability and flexibility, rapid application, and excellent conformability to irregular wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The above and other objects and features of the present disclosure will become apparent from the following description of the present disclosure when taken in conjunction with the accompanying drawings.

[0042] Figure 1 A schematic diagram of the material composition and application process of a spray-type biomimetic dressing composition provided in an embodiment of the present invention;

[0043] Figure 2 To verify the chemical structure of poly(methacrylated gelatin) (GelMA) and poly(lactic acid-propylene glycol-lactic acid) dimethacrylate (PGLADMA), Fourier transform infrared spectroscopy and 1 H NMR spectroscopy test results;

[0044] Figure 3 The spontaneous water / oil separation of GelMA (in the aqueous phase) and PGLADMA (in the oil phase) in the presence of different mass fractions of calcium chloride (CaCl2) after vigorous mixing.

[0045] Figure 4 The macroscopic image of the double-layer anti-scar dressing formed after photocrosslinking in the presence of different mass fractions of calcium chloride (CaCl2), as well as the scanning electron microscopic image of the material and the interface between the two layers;

[0046] Figure 5 This is a diagram showing the strong tissue adhesion and joint motion adaptability of the bionic dressing of the present invention;

[0047] Figure 6 Schematic diagram of mechanical property test results of the bionic dressing of the present invention and the single layer formed by the oil phase or the water phase;

[0048] Figure 7The figures show the hemostatic performance test results of the bionic dressing of the present invention using a rat tail amputation model as an example, wherein A: a photograph showing the hemostatic effect of the bionic dressing of the present invention; B: quantification of clotting time; C: relative blood loss ratio, calculated by weighing the filter paper that accounts for the blood; D: a photograph showing the amount of bleeding observed by absorbing the seeping blood through the filter paper.

[0049] Figure 8 The results of the bactericidal evaluation of the oil phase (photo-crosslinkable PGLADMA + triclosan) of the biomimetic dressing of the present invention are shown using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as examples;

[0050] Figure 9 The biocompatibility evaluation results of the oil phase (photocrosslinkable PGLADMA + triclosan) and the water phase (GelMA + calcium chloride solution) in the biomimetic dressing composition of the present invention are shown in FIG. CL+ indicates the presence of collagenase, and CL- indicates the absence of collagenase.

[0051] Figure 10 The results of the in vitro angiogenic ability evaluation of the aqueous phase (GelMA + calcium chloride solution) using human umbilical vein endothelial cells (HUVEC) as an example are shown, along with microfluorescence images and quantitative evaluation of newly formed vascular branches.

[0052] Figure 11 Taking the full-thickness skin wound model of rats infected with Staphylococcus aureus as an example, the wound healing effect of the bionic dressing of the present invention was evaluated based on the wound area change and healing ratio;

[0053] Figure 12 The anti-scarring therapeutic effect of the double-layer biomimetic dressing was evaluated by Masson staining and collagen immunofluorescence staining of rat skin tissue. DETAILED DESCRIPTION

[0054] definition

[0055] Throughout this application, where compositions are described as having, including, or comprising specific components, or processes are described as having, including, or comprising specific process steps, it is contemplated that the compositions taught by the present invention may also consist essentially of or consist of the recited components, and that the processes taught by the present invention may also consist essentially of or consist of the recited process steps.

[0056] In this application, when an element or component is referred to as being included in and / or selected from a list of enumerated elements or components, it should be understood that the element or component can be any one of the enumerated elements or components, or the element or component can be selected from a group consisting of two or more of the enumerated elements or components. In addition, it should be understood that the elements and / or features of the compositions or methods described herein can be combined in various ways, whether explicitly or implicitly herein, without departing from the spirit and scope of the present teachings.

[0057] Should be understood that, as long as the present invention teachings remain operable, the order of steps or the order in which certain actions are performed is not important.In addition, two or more steps or actions can be performed simultaneously.

[0058] Unless otherwise expressly stated, the use of the singular herein includes the plural (and vice versa). Furthermore, when the term "about" is used before a quantitative value, the present teachings also include the specific quantitative value itself, unless otherwise specifically stated. As used herein, the term "about" refers to a variation of ±10%, ±7%, ±5%, ±3%, ±1%, or ±0% of the nominal value, unless otherwise stated or inferred.

[0059] In the present invention, the expression "optionally" refers to two embodiments in which the features (eg, components, steps, etc.) defined by the term may or may not be present.

[0060] The "normal temperature" condition mentioned in the present invention refers to general temperature or room temperature, which is usually defined as 20-25°C, for example, a temperature condition of 25°C.

[0061] Advantages and features of the present invention will become more apparent from the following description of the best mode and illustrative examples.The scope of the present invention is not limited to any specific embodiments described herein.

[0062] The present invention provides a biomimetic dressing forming composition comprising an aqueous phase and an oil phase, wherein

[0063] The oil phase contains a hydrophobic prepolymer or a hydrophobic monomer, wherein the hydrophobic prepolymer or the hydrophobic monomer has a first photopolymerizable functional group, and the oil phase has a hydrophobicity of less than 10 at room temperature. 6 Intrinsic viscosity in mPa·s;

[0064] The aqueous phase contains a hydrophilic hydrogel prepolymer or a hydrophilic hydrogel monomer and an active ingredient, wherein the hydrophilic hydrogel prepolymer or the hydrophilic hydrogel monomer has a second photopolymerizable functional group, and the aqueous phase has a photocatalytic activity of less than 10 6 Intrinsic viscosity in mPa·s;

[0065] The first photopolymerizable functional group and the second photopolymerizable functional group contain a -C=C- bond and are capable of polymerization and / or crosslinking initiated by light, and

[0066] After applying the composition, the oil phase and the water phase can self-separate and form a biomimetic dressing having a double-layer cross-linked structure.

[0067] The biomimetic dressing-forming composition of the present invention can be conveniently formed into a biomimetic dressing. During application, the oil and water phases in the composition can be uniformly mixed (e.g., by shaking) and then applied (e.g., sprayed or coated) to the wound. The oil phase and water phase in the composition can rapidly and spontaneously separate into a double-layer structure, which is then cured by photoinitiated polymerization / crosslinking to form a double-layer structure consisting of an adjacent skin-conforming layer and an outer layer, wherein the skin-conforming layer is formed by the water phase and the outer layer is formed by the oil phase. In certain embodiments, the photoinitiated polymerization / crosslinking is performed by irradiating the oil phase and the water phase with natural light or ultraviolet light after the composition is applied, preferably by irradiating with ultraviolet light to cause the prepolymers or monomers in the oil phase and the water phase to react.

[0068] In one embodiment, the aqueous phase and the oil phase in the biomimetic dressing forming composition according to the present invention may have an intrinsic viscosity of less than about 1000 mPa·s at room temperature, preferably an intrinsic viscosity of less than about 100 mPa·s, 90 mPa·s, 80 mPa·s, 70 mPa·s, 65 mPa·s, 60 mPa·s, 55 mPa·s, 50 mPa·s, 45 mPa·s, 40 mPa·s, 35 mPa·s, 30 mPa·s, 25 mPa·s, 20 mPa·s, 15 mPa·s, 10 mPa·s, 9 mPa·s, 8 mPa·s, 5 mPa·s, 4 mPa·s, 3 mPa·s or 2 mPa·s or close to 1 mPa·s.

[0069] In one embodiment, the aqueous phase and the oil phase in the biomimetic dressing forming composition according to the present invention may have an intrinsic viscosity of less than 1-1000 mPa·s at room temperature, preferably an intrinsic viscosity of 1-100 mPa·s, 50-90 mPa·s, 40-80 mPa·s, 30-70 mPa·s, 25-65 mPa·s, 20-60 mPa·s, 15-55 mPa·s, 10-50 mPa·s, 5-45 mPa·s, 4-40 mPa·s, 3-35 mPa·s, 2-30 mPa·s, 1-25 mPa·s or 1-20 mPa·s.

[0070] In the biomimetic dressing-forming composition of the present invention, the hydrophobic prepolymer or hydrophobic monomer contained in the oil phase can be a biocompatible hydrophobic prepolymer or monomer, which can be polymerized or cross-linked by photoinitiation to form a hydrophobic polymer. The hydrophilic prepolymer or hydrophilic monomer contained in the aqueous phase can be a biocompatible hydrophilic prepolymer or monomer, which can be polymerized or cross-linked by photoinitiation to form a hydrophilic hydrogel polymer.

[0071] In certain embodiments, the first photopolymerizable functional group may be one or more of acrylate, methacrylate, 1,6-hexanediol diacrylate, or β-hydroxyethyl methacrylate.

[0072] In certain embodiments, the hydrophobic prepolymer or hydrophobic monomer further has one or more hydrophobic groups selected from the following: C10 to C20 hydrocarbon groups, ethers, amine groups, and amide groups, etc., wherein the C10 to C20 hydrocarbon groups may have single bonds, double bonds, or triple bonds.

[0073] In certain embodiments, the hydrophobic prepolymer or hydrophobic monomer itself can serve as the solvent in the oil phase, without the need for the addition of other organic solvents. In certain embodiments, the viscosity of the oil phase can also be adjusted by adding other organic solvents. Examples of organic solvents useful in the present invention include anhydrous ethanol and dichloromethane.

[0074] According to the present invention, examples of the hydrophobic prepolymer or hydrophobic monomer may be selected from one or more of poly(lactic acid-propylene glycol-lactic acid) dimethacrylate, polypropylene glycol diacrylate, polypropylene glycol dimethacrylate, polypropylene acrylate, and polymethyl methacrylate.

[0075] According to the present invention, the oil phase and / or aqueous phase may further comprise other functional material components, such as an antimicrobial active ingredient. In a preferred embodiment, the antimicrobial active ingredient contained in the oil phase is triclosan (TCS) and / or curcumin. Because the oil phase has a slower degradation rate than the aqueous phase, the antimicrobial active ingredient is preferably contained in the oil phase to facilitate long-term antimicrobial effects.

[0076] For example, when triclosan is added to the oil phase, the antibacterial effect of the biomimetic dressing of the present invention can be further enhanced, thereby facilitating rapid wound healing. In the present invention, curcumin can alleviate inflammation by regulating the expression of inflammatory-related factors and cytokines, and reduce oxidative stress by neutralizing free radicals. It also has antibacterial activity against most bacteria and fungi, and can promote blood vessel and tissue regeneration, promote the proliferation of fibroblasts, and improve blood supply to the wound area.

[0077] In certain embodiments, the aqueous phase of the biomimetic dressing-forming composition may also contain antimicrobial active ingredients such as triclosan (TCS) and / or curcumin.

[0078] In one embodiment, the concentration of the antimicrobial active ingredient in the oil phase is 0-20% by weight, preferably 1-10% by weight, more preferably 2-7% by weight, 3-8% by weight or 5% by weight. For example, the concentration of the antimicrobial active ingredient in the oil phase is 1% by weight, 1.5% by weight, 2% by weight, 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight, 5% by weight, 5.5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 15% by weight or 20% by weight, or any range therebetween.

[0079] According to the present invention, the oil phase and / or the aqueous phase of the biomimetic dressing forming composition further contain a first photoinitiator for initiating polymerization and / or crosslinking of a hydrophobic prepolymer or a hydrophobic monomer, or a second photoinitiator for initiating polymerization and / or crosslinking of a hydrophilic hydrogel prepolymer or a hydrophilic hydrogel monomer. The first / second photoinitiator that can be used in the present invention can be: a quinolone compound, such as 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959), di(2,4,6-trimethylbenzoyl)phenylphosphine oxide (Irgacure 819), benzylquinolone, camphorquinone (CQ); an organic dye, such as rhodamine B, phthalocyanine, eosin Y (EY); a metal complex, such as lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), copper (II) phthalocyanine (Copper phthalocyanine), ruthenium pyridine complex Ru(II)(bpy)3]2+ / sodium sulfate (SPS); dibenzothiazole derivatives, such as 2,4,6-triphenyldibenzothiazole (TPD), 2,6-dimethylbenzothiazole; or phenol derivatives, such as phenol-methoxyacrylate or hydroxybenzoate. In certain embodiments, specific examples of the first photoinitiator contained in the oil phase of the biomimetic dressing-forming composition for initiating polymerization and / or crosslinking of the hydrophobic prepolymer or hydrophobic monomer may include di(2,4,6-trimethylbenzoyl)phenylphosphine oxide (Irgacure819), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and the like. Examples of the second photoinitiator included in the composition for initiating polymerization and / or crosslinking of the hydrophilic hydrogel prepolymer or hydrophilic hydrogel monomer include 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone or camphorquinone (CQ).

[0080] In certain embodiments, the second photopolymerizable functional group can be acrylic acid, acrylamide, methacrylamide, or the like.

[0081] In certain embodiments, the hydrophilic prepolymer or the hydrophilic monomer further has a hydrophilic group selected from one or more of the following: a thiol group, a carboxyl group, and a hydroxyl group.

[0082] In certain embodiments, the concentration of the hydrophilic prepolymer or the hydrophilic monomer in the aqueous phase can be 1-30 weight %. Preferably, the concentration of the aqueous prepolymer or the hydrophilic monomer in the aqueous phase can be 3 weight %, 5 weight %, 7 weight %, 9 weight %, 11 weight %, 13 weight %, 15 weight %, 17 weight %, 19 weight %, 20 weight %, 21 weight %, 23 weight %, 25 weight %, 27 weight %, 29 weight %, 30 weight %, or any numerical range therebetween. More preferably, the concentration of the aqueous prepolymer or the hydrophilic monomer in the aqueous phase is 5-20 weight %. According to the present invention, the aqueous phase viscosity can be adjusted by regulating the concentration of the hydrophilic prepolymer or the hydrophilic monomer in the aqueous phase or regulating the water content in the aqueous phase.

[0083] According to the present invention, examples of the hydrophilic hydrogel prepolymer or hydrophilic hydrogel monomer may be selected from one or more of methacrylated gelatin, acrylated gelatin, methacrylated hyaluronic acid, acrylated hyaluronic acid, methacrylated chitosan, acrylated chitosan and hydrophilic polyethylene glycol diacrylate.

[0084] In certain embodiments, the aqueous phase of the biomimetic dressing composition may further include an active ingredient soluble therein, which may be a hemostatic active ingredient and / or a wound healing active ingredient, such as a water-soluble salt or thrombin, and a wound healing active ingredient such as a growth factor, thereby meeting the precision medical needs of different wound conditions. The water-soluble salt may be, for example, calcium ions (such as CaCl2). The growth factor may be, for example, vascular endothelial growth factor.

[0085] In the case of adding calcium ions in the aqueous phase, the biomimetic dressing of the present invention can activate the coagulation cascade reaction, thereby further promoting rapid hemostasis. In certain embodiments, the soluble calcium salt (Ca 2+ ) in the aqueous phase has a concentration of 0-70 wt%. For example, the soluble calcium salt (Ca 2+ ) in the aqueous phase at a concentration of 0.1 wt%, 0.5 wt%, 1 wt%, 3 wt%, 5 wt%, 8 wt%, 10 wt%, 12 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 50 wt%, 60 wt% or 70 wt% or any range therebetween, preferably 5-30 wt%, more preferably 5-20 wt% or 5-10 wt%.

[0086] The present inventors have found that by adjusting the calcium salt concentration within the above range, the formed suspension can also be maintained in an oil phase / water phase mixed state within a desired period of time (e.g., within 5 seconds, within 10 seconds, within 15 seconds, or within 20 seconds or a longer period of time) before light curing, so as to facilitate application by the user.

[0087] In the above embodiments of the present invention, the amount of photoinitiator in the oil phase or the aqueous phase should be sufficient to initiate polymerization or crosslinking reaction of the prepolymer or monomer therein, for example, the amount of the first photoinitiator present in the oil phase can be 0.1-5 weight%, for example, 0.5 weight%, 1 weight%, 1.5 weight%, 2 weight%, 2.5 weight%, 3 weight%, 3.5 weight%, 4 weight%, 4.5 weight%, 5 weight% or any numerical range therebetween; and / or the amount of the second photoinitiator present in the aqueous phase can be 0.05-3 weight%, for example, 0.1 weight%, 0.25 weight%, 0.3 weight%, 0.4 weight%, 0.5 weight%, 1 weight%, 1.5 weight%, 2 weight%, 2.5 weight%, 3 weight% or any numerical range therebetween. The degree of crosslinking of the hydrophobic polymer and / or hydrophilic hydrogel obtained after crosslinking can be, for example, at least 50%, preferably 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%.

[0088] In certain embodiments, the volume ratio of the oil phase to the water phase of the biomimetic dressing-forming composition is 3:1 to 1:3, preferably 2:1, and more preferably 1:1.

[0089] In certain embodiments, the biomimetic dressing forming composition may further comprise additional additives in the oil phase and / or the water phase to achieve additional functions of the dressing, and the additives may be, for example, one or more of the following: antimicrobial agents, odor control agents, colorants, wound pH, and blood glucose monitoring agents.

[0090] In certain embodiments, at the interface between the skin-conforming layer and the outer layer, cross-linking exists between the hydrophilic hydrogel and the hydrophobic polymer formed after cross-linking and curing, so that there is a strong bonding force at the interface between the skin-conforming layer and the outer layer, thereby avoiding interlayer peeling.

[0091] In a preferred embodiment, the biomimetic dressing provided by the present invention forms a composition comprising poly (lactic acid-propylene glycol-lactic acid) dimethacrylate (abbreviated as PGLADMA or PLD) and triclosan in the oil phase, polymethacrylated gelatin (abbreviated as GelMA) and calcium salt in the aqueous phase, and a photoinitiator for initiating photopolymerization may be included in the oil phase and the aqueous phase. Due to the acrylic acid or acryloyl functional groups present in PGLADMA and GelMA, the biomimetic dressing forms a composition that can be cured by photocrosslinking within 100 seconds, and a stronger bonding force can be obtained at the interface between the skin-fitting layer and the outer layer to avoid interlayer peeling. In addition, due to the tissue adhesion of GelMA, and the elasticity of GelMA and PGLADMA, the biomimetic dressing formed after curing can be firmly attached to the wound site and adapt to joint movement. In addition, relatively soft and hydrophilic calcium salt (Ca 2+ ) carrier GelMA can activate the coagulation cascade and achieve rapid hemostasis. At the same time, the relatively hard and hydrophobic PGLADMA layer loaded with triclosan (TCS) can act as a protective crust to maintain a moist and sterile environment. These properties work synergistically, enabling the dressing of the present invention to inhibit inflammatory pathways (such as TNF-α), increase M2 macrophage polarization, promote the transition from inflammation to proliferation, and jointly activate and coordinate cGMP / PKG-Wnt / Ca 2+ signaling pathways, effectively promoting vascular reconstruction and being particularly beneficial for achieving scar-free healing.

[0092] The biomimetic dressing forming composition provided by the present invention can be stored away from light before use, thereby minimizing the premature reaction of prepolymers or monomers in the oil phase and the water phase, thereby avoiding affecting the use of the composition.

[0093] In certain embodiments, the composition does not contain any emulsifier or surfactant to facilitate rapid separation of the oil phase and the aqueous phase and reduce the difficulty of subsequent wound cleaning and the risk of infection. For example, in certain embodiments, the composition does not contain Span 80 or Tween 20.

[0094] In addition, the biomimetic dressing-forming composition of the present invention can be formed into various dosage forms, generally a liquid preparation, such as a spray or other forms of liquid preparation.

[0095] When forming a biomimetic dressing from a biomimetic dressing composition, the oil phase and aqueous phase are mixed uniformly and then applied to the upward-facing wound surface. Due to the incompatibility of the oil and water phases, the composition rapidly separates after application. Under the action of gravity, the denser aqueous phase settles to the lower layer. Due to its good affinity with the skin, it can adhere to the wound surface; the less dense oil phase is located above the aqueous phase. Under the induction of ultraviolet light or natural light, the polymers in the two phases are polymerized or cross-linked, forming the biomimetic dressing of the present invention. It should be understood that the biomimetic dressing composition of the present invention can be applied in a variety of ways, such as by spraying, coating, or extrusion.

[0096] Typically, the biomimetic dressing-forming composition of the present invention cures within 100 seconds, preferably within 80 seconds, within 60 seconds, within 50 seconds, within 40 seconds, within 30 seconds, within 20 seconds, within 10 seconds, or less than 10 seconds after photoinitiation.

[0097] The curing time can be adjusted by adjusting the photoinitiator concentration within the above range. For example, increasing the photoinitiator concentration can shorten the curing time. For example, adjusting the photoinitiator concentration in the oil-water phase (e.g., Irgacure 819 and Irgacure 2959) from 1 wt% to 2 wt% can shorten the curing time to under 30 seconds.

[0098] The following describes specific embodiments of the present invention with reference to the accompanying drawings. It should be understood that various modifications are possible without departing from the scope of the present invention as described above. The following embodiments are provided for illustration only.

[0099] Example

[0100] Material

[0101]

[0102]

[0103] In the following examples, the intrinsic viscosity of the oil phase or the water phase was measured at room temperature using a rheometer in a rotational mode.

[0104] Preparation of biomimetic dressing-forming composition

[0105] Preparation Example 1

[0106] In this example, a biomimetic dressing-forming composition comprising PGLADMA and GelMA as prepolymers was prepared and prepared as a spray or a liquid preparation for coating. The specific preparation steps are as follows: First, 1 weight percent of the first photoinitiator Irgacure 819 was dissolved in the liquid PGLADMA as a prepolymer, and 1 weight percent of the second photoinitiator Irgacure 2959 was dissolved in a 10 weight percent GelMA aqueous solution. The viscosity of the oil phase was measured to be 200 mPa·S and the viscosity of the water phase was 100 mPa·S. After the photoinitiator was completely dissolved, the oil phase and the water phase were mixed in a spray bottle in a 1:1 ratio and kept away from light for use.

[0107] Preparation Example 2

[0108] In this embodiment, a biomimetic dressing composition comprising PGLADMA and GelMA as prepolymers was prepared and prepared as a spray or a liquid preparation for coating. Calcium ions Ca were also mixed into the aqueous phase as the lower layer. 2+ , the oil phase as the upper layer also contains triclosan. The specific preparation steps are as follows: first, 1 weight% of the first photoinitiator Irgacure819 is dissolved in the liquid PGLADMA as a prepolymer, and 1 weight% of the second photoinitiator Irgacure2959 is dissolved in a 10 weight% GelMA aqueous solution. After the photoinitiator is completely dissolved, 5 weight% of triclosan is added to the upper oil phase and 10 weight% of calcium chloride is added to the lower aqueous phase to prepare a biomimetic dressing BDM. The viscosity of the oil phase of the prepared biomimetic dressing BDM was measured to be 200mPa·S, and the viscosity of the water phase was 100mPa·S. After sufficient stirring and dissolution, the oil phase and the water phase are mixed in a spray bottle in a 1:1 ratio and protected from light for use.

[0109] Preparation Example 2A and Preparation Examples 3-7

[0110] In this example, a biomimetic dressing forming composition was prepared using the same method as in Example 2, except that the concentrations of triclosan and calcium chloride were adjusted.

[0111] The concentrations of triclosan and calcium chloride in Preparation Examples 1-7 are listed in Table 1 below.

[0112] Table 1

[0113]

[0114] Preparation Examples 8-10

[0115] In this example, the biomimetic dressing forming composition is prepared by the same method as in Example 2, except that the viscosity of the oil phase and the water phase is adjusted, for example, by adjusting the amount of the solvent.

[0116] Table 2

[0117]

[0118] The bionic dressing of the present invention can be successfully obtained by using the bionic dressing forming composition in the above preparation examples.

[0119] Formation of biomimetic dressings

[0120] Figure 1 The materials contained in the biomimetic dressing forming composition provided in Preparation Examples 1-10 of the present invention and the forming process of the biomimetic dressing are shown. Figure 1 As shown, in the composition, the oil phase contains PGLADMA and the aqueous phase contains GelMA, and both PGLADMA and GelMA can be rapidly photocrosslinked under ultraviolet light irradiation. When the composition is a spray, the composition in the form of a spray is shaken to mix the oil phase and the aqueous phase and then sprayed onto the skin wound site. When the composition is a liquid preparation for coating, the composition is shaken to mix the oil phase and the aqueous phase and then applied to the skin wound site. Due to the incompatible characteristics of the oil and water phases, the composition will quickly stratify after application. Under the action of gravity, the water phase with higher density is deposited in the lower layer. Due to its good affinity with the skin, it can adhere to the wound surface. The oil phase with lower density is located in the upper layer of the water phase. Under the initiation of ultraviolet light or natural light, the polymers in the two phases are polymerized or crosslinked to form the bionic dressing of the present invention.

[0121] Figure 2 A-2B shows Fourier transform infrared spectroscopy (FTIR) and 1 H NMR spectroscopy ( 1 H NMR) test results. Figure 2 In A, the 1640 cm -1 The position reflects the characteristic peaks of the C=C double bonds of the two materials; Figure 2 B's 1 In the H NMR results, characteristic peaks of C=C double bonds appeared at 5.5 ppm and 5.28 ppm for GelMA, and at 6.21 and 5.6 ppm for PGLADMA.

[0122] Figure 3The spontaneous water / oil separation process without the addition of CaCl2 and with the intervention of calcium chloride (CaCl2) at different weight fractions (Preparation Examples 1-4) is shown. Each sample contains GelMA and PGLADMA in the water phase and the oil phase, respectively. G-PLD (Preparation Example 1) means that no CaCl2 is added, G / Ca5-PLD (Preparation Example 3), G / Ca10-PLD (Preparation Example 2A) and G / Ca20-PLD (Preparation Example 4) mean that different concentrations of CaCl2 (5 wt%, 10 wt%, 20 wt%) are added to the GelMA aqueous solution. Figure 3 As shown in the figure, for samples without CaCl2 and samples mixed with different concentrations of CaCl2, GelMA (aqueous phase) and PGLADMA (oil phase) can achieve rapid stratification after mixing and shaking. For samples mixed with CaCl2, rapid stratification can be achieved within 15 seconds after mixing and shaking. For samples without CaCl2, G-PLD can also achieve rapid stratification within a few minutes after mixing and shaking.

[0123] Figure 4 Macroscopic images and scanning electron microscopy (SEM) images of the material and crosslinked interface of a biomimetic dressing formed after photocrosslinking according to an embodiment of the present invention, wherein the biomimetic dressing is formed from the compositions of Preparation Example 3 and Preparation Example 2A, respectively. Both the macroscopic image and the SEM results demonstrate the layered structure of GelMA and PGLADMA after crosslinking.

[0124] Figure 5 The photographs in the figure show the application of the biomimetic dressing-forming composition of Preparation Example 1 of the present invention and demonstrate the strong tissue adhesion and excellent adaptability to joint motion of the formed biomimetic dressing, indicating that the biomimetic dressing can closely adhere to tissue and adapt to joint motion. The biomimetic dressings formed from the biomimetic dressing-forming compositions of Preparation Examples 2-10 also achieve the same strong tissue adhesion and excellent adaptability to joint motion.

[0125] Performance test of the formed biomimetic dressing

[0126] In this example, the mechanical properties, hemostatic and bactericidal properties, and biocompatibility of the biomimetic dressing formed were tested.

[0127] The test in this embodiment was conducted under the following conditions / standards.

[0128] 1. Mechanical properties test: The mechanical properties of biomimetic excipients were tested according to ASTM F2458-05. GelMA, PGLADMA, and double-layer GelMA / PGLADMA specimens of 20 × 5 mm were prepared and stretched at a rate of 1 mm / min using a double-arm mechanical tensile tester at room temperature. The mechanical properties were calculated, where the elastic modulus of tension = stress / strain. For example, the test method in Theocharidis G, Yuk H, Roh H, et al. A strain-programmed patch for the healing of diabetic wounds [J]. Nature biomedical engineering, 2022, 6(10): 1118-1133 can be referenced.

[0129] 2. Hemostatic performance: The hemostatic performance of biomimetic excipients can be studied, for example, by referring to the method in Guo Y, Wang Y, Zhao X, et al. Snake extract–laden hemostatic bioadhesive gel cross-linked by visible light [J]. Science Advances, 2021, 7(29): eabf9635.

[0130] 3. Bactericidal performance: The bactericidal performance of biomimetic excipients can be studied, for example, by referring to the method in He W, Bai J, Chen X, et al. Reversible dougong structured receptor–ligand recognition for building dynamic extracellular matrix mimics[J]. Proceedings of the National Academy of Sciences, 2022, 119(8): e2117221119.

[0131] 4. Biocompatibility: The biocompatibility of biomimetic excipients can refer to ISO-10993 standard. Soak in full culture medium at 37°C for 24 hours, then use the extracted culture medium at 1×10 4 cells / cm 2 Cells were seeded into 24-well plates at a density of 1:1. After incubation for 1, 2, and 3 days, cell viability and cell proliferation were assessed using a live / dead cell assay kit (Thermo Fisher, Hong Kong) and a CCK-8 kit (Sigma-Aldrich, Hong Kong), respectively.

[0132] Figure 6 A is a schematic diagram of the mechanical properties test results of the aqueous phase in Preparation Example 1-3 after photoinduced crosslinking and curing. Figure 6 As shown in Figure A, the elastic modulus of the skin-adhering layer formed by GelMA mixed with different CaCl2 contents after curing is between about 85-96 kPa. Figure 6 B is a schematic diagram of the mechanical property test results of the oil phase in Preparation Example 1 after photoinitiated cross-linking and curing. The elastic modulus of the outer layer formed by PGLADMA after curing is approximately 13 MPa after cross-linking, indicating that the outer layer structure has good tensile properties after cross-linking. Figure 6 C shows a schematic diagram of the mechanical property test results of the compositions in Preparation Example 2A and Preparation Example 3 after photoinitiated cross-linking and curing, with an elastic modulus of approximately 4-10 MPa. The inset shows the SEM results of the double-layer structure after stretching, indicating that a clear cross-linked interface of the double-layer dressing can still be maintained after stretching.

[0133] Figure 7 The results of the hemostatic performance test of the double-layer anti-scar dressing using the rat tail amputation model provided in the embodiments of the present invention are shown. The blank control represents the rat tail amputated without any treatment, and the hemostasis is achieved solely by its own coagulation mechanism. The GelMA sample represents the absence of calcium chloride in the aqueous phase. The G / Ca5 and G / Ca10 samples represent the addition of 5% and 10% by weight of calcium chloride in the aqueous phase, respectively. Figure 7 As shown in the photo in A, after cutting off 30% of the rat's tail, the rat's tail would bleed profusely. The dressing composition in this example can achieve a rapid hemostasis effect. Figure 7 As shown in Figure 7D, compared with the blank control, the dressings formed by the compositions of Preparation Examples 1-3 of the present invention can achieve effective hemostasis. In the case of containing calcium ions, compared with sample GelMA, samples G / Ca5 and G / Ca10 can achieve shorter hemostasis time and less blood loss. Among them, the hemostatic effect is best when containing 10% by weight of CaCl2, and rapid hemostasis is achieved within 90 seconds.

[0134] Figure 8 The results of the evaluation of the bactericidal ability of dressings formed from compositions containing PGLADMA and triclosan (TCS) in the oil phase (Preparation Examples 5-7) are shown, taking Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as examples.

[0135] Figure 8 A shows the inhibition zone test, where larger transparent circles represent greater antibacterial efficacy. As shown, the dressing containing TCS in the oil phase exhibited greater antibacterial efficacy, with the antibacterial effect becoming even more pronounced as the TCS content increased to 10% by weight. Figure 8 B shows the quantitative results of the inhibition zone experiment, which Figure 8 The area of ​​the transparent circle A was calculated. As the TCS content increased, the antibacterial effect became more significant.

[0136] Figure 9 A to Figure 9 C shows the biocompatibility evaluation results of the dressings formed from the compositions of Preparation Examples 1 and 5-7. Figure 9 A shows the effect of mixing different TCS contents on the compatibility of 3T3 cells. The cells indicated by gray highlights are living cells. Figure 9 The results of A showed that TCS had no toxicity to cells below a concentration of 5% and was only slightly toxic at a concentration of around 10%. Figure 9 B shows the quantitative results of cell viability, and above 95% indicates good compatibility. Figure 9 As shown in Figure B, the dressings formed from the compositions of Preparation Examples 1 and 5-7 of the present invention all achieved good compatibility, and the cell viability was above 95%. Figure 9 C shows the cell proliferation experiment, and the OD value indicates the cell number. Figure 9 C shows that the dressings formed from the compositions of Preparation Examples 1 and 5-7 of the present invention all showed a significant increase in the number of cells.

[0137] Figure 9 D- Figure 9 The results of F show that the addition of collagenase (CL+ indicates the addition of collagenase, CL- indicates the absence of collagenase) is beneficial to further enhance the antibacterial effect of the dressing of the present invention, and the obtained dressing still has good biocompatibility.

[0138] Figure 10 A- Figure 10 B is the result of evaluating the in vitro angiogenesis ability of the dressing after solidification of the aqueous phase (GelMA+calcium chloride solution) in the composition of Preparation Examples 1-3, using human umbilical vein endothelial cells (HUVEC) as an example. Figure 10 A is the result of the cell tube formation experiment, which shows the angiogenesis ability of endothelial cells. The denser the network and the more nodes, the better the angiogenesis ability. Figure 10 B is the quantification of angiogenesis, and the vertical axis shows the number of cross-linked nodes in the vascular network calculated by Image J software. Figure 10 A- Figure 10 As shown in Figure B, the dressings formed by the present invention have strong angiogenesis ability, especially when containing collagenase and calcium ions, the angiogenesis ability is improved (a maximum of more than 60 nodes are obtained in 6 hours).

[0139] Figure 11In A-11C, a full-thickness skin wound model of rats infected with Staphylococcus aureus was used as an example. The wound healing effects of the bionic dressing (BDM) formed by the composition of Preparation Example 2 of the present invention, as well as the bionic dressing formed by the PLD / TCS5 monolayer (formed after curing the oil phase containing PLD and 5 wt% TCS) and the G / Ca10 monolayer (formed after curing the aqueous phase containing GelMA and 10 wt% CaCl2) were evaluated based on the wound area change and healing ratio. Figure 11 The photos in A-11C show a rat skin infection defect model and the wound repair process in rats. As shown, the dressings of the present invention have strong wound repair capabilities, and the dressing containing TCS, in particular, achieves significantly better wound repair results than the commercially available control product, Fibrin glue. Figure 11 The quantitative results in D-11E also showed this trend. In particular, BDM treatment achieved the best wound healing effect. At 14 days, the wound area treated with BDM was almost invisible and no scar was found, corresponding to a wound repair rate of approximately 99-100%.

[0140] Figure 12 The anti-scarring effects of the biomimetic dressing (BDM) formed by the composition of Preparation Example 2 of the present invention, and the biomimetic dressing formed by the PLD / TCS5 monolayer (formed after solidification of an oil phase containing PLD and 5 wt% TCS) and the G / Ca10 monolayer (formed after solidification of an aqueous phase containing GelMA and 10 wt% CaCl2) are shown by Masson staining of rat skin tissue and immunofluorescence staining of collagen.

[0141] Figure 12 A shows the Masson staining results. The more lighter gray parts there are, the better the wound repair is. As shown in the figure, BDM shows the largest area of ​​lighter gray parts, indicating the best wound repair effect.

[0142] Figure 12 The quantitative results of Masson staining shown in B showed that compared with other control groups, the BDM group had significantly more new collagen deposition (about 40%) and better skin repair effect.

[0143] Figure 12 C and Figure 12 D shows the results of immunofluorescence staining for type I and type III collagen, which showed that the BDM group had less type I collagen (lighter gray area) and more type III collagen (dark area).

[0144] Figure 12E shows the results of collagen staining area quantification, which showed that the type I collagen-positive area in the BDM group was lower than that in the other control groups, while the type III collagen-positive area (about 40%) was significantly higher than that in the other control groups.

[0145] Figure 12 Figure F shows the quantitative ratio of type I to type III collagen, with lower values ​​indicating better wound repair and less scarring. As shown in the figure, the BDM group had the lowest quantitative ratio of type I to type III collagen, indicating that the BDM group according to the present invention had a better wound repair effect and produced less scarring than the control group.

[0146] The above description of the embodiments is intended to facilitate understanding and application of the present invention by those skilled in the art. It will be apparent that those skilled in the art can readily make various modifications to these embodiments and apply the general principles described herein to other embodiments without requiring inventive effort. Therefore, the present invention is not limited to the specific embodiments disclosed herein, and improvements and modifications made by those skilled in the art based on the principles of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A biomimetic dressing forming composition comprising an aqueous phase and an oil phase, wherein The oil phase contains a hydrophobic prepolymer or a hydrophobic monomer, wherein the hydrophobic prepolymer or the hydrophobic monomer has a first photopolymerizable functional group, and the oil phase has a hydrophobicity of less than 10 at room temperature. 6 an intrinsic viscosity of mPa·s, for example, an intrinsic viscosity of 1-1000 mPa·s, 10-200 mPa·s, 5-100 mPa·s, or 1-80 mPa·s; The aqueous phase contains a hydrophilic hydrogel prepolymer or a hydrophilic hydrogel monomer and an active ingredient, wherein the hydrophilic hydrogel prepolymer or the hydrophilic hydrogel monomer has a second photopolymerizable functional group, and the aqueous phase has a photocatalytic activity of less than 10 6 an intrinsic viscosity of mPa·s, for example, an intrinsic viscosity of 1-1000 mPa·s, 20-200 mPa·s, 10-100 mPa·s, 5-50 mPa·s, or 1-30 mPa·s; The first photopolymerizable functional group and the second photopolymerizable functional group contain a -C=C- bond and are capable of polymerization and / or crosslinking initiated by light, and After application of the composition, the oil phase and the water phase can self-separate and form a biomimetic dressing having a double-layer cross-linked structure of a hydrophobic polymer and a hydrophilic hydrogel.

2. The biomimetic dressing-forming composition according to claim 1, wherein the first photopolymerizable functional group and the second photopolymerizable functional group comprise one or more of acrylate, methacrylate, acrylamide, methacrylamide, styrene, N-vinyl pyrrolidone, hydroxybutyl vinyl ether, diethylene glycol divinyl ether or phenyl glycidyl ether.

3. The biomimetic dressing forming composition according to claim 1 or 2, wherein the hydrophobic prepolymer or hydrophobic monomer comprises one or more of poly(lactic acid-propylene glycol-lactic acid) dimethacrylate, polypropylene glycol diacrylate, polypropylene glycol dimethacrylate, polypropylene acrylate and polymethyl methacrylate.

4. The biomimetic dressing forming composition according to any one of claims 1 to 3, further comprising a first photoinitiator for initiating polymerization and / or crosslinking reactions of the hydrophobic prepolymer or hydrophobic monomer, preferably, the first photoinitiator comprises di(2,4,6-trimethylbenzoyl)phenylphosphine oxide or lithium phenyl-2,4,6-trimethylbenzoylphosphinate.

5. The biomimetic dressing forming composition according to any one of claims 1 to 4, wherein the hydrophilic hydrogel prepolymer or hydrophilic hydrogel monomer comprises one or more of methacrylated gelatin, acrylated gelatin, methacrylated hyaluronic acid, acrylated hyaluronic acid, methacrylated chitosan, acrylated chitosan and hydrophilic polyethylene glycol diacrylate.

6. The biomimetic dressing forming composition according to any one of claims 1 to 5, further comprising a second photoinitiator for initiating polymerization and / or crosslinking reactions of the hydrophilic hydrogel prepolymer or hydrophilic hydrogel monomer, preferably the second photoinitiator comprises 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone or camphorquinone.

7. The biomimetic dressing forming composition according to any one of claims 1 to 6, wherein the active ingredient in the aqueous phase is selected from hemostatic active ingredients, such as water-soluble calcium salts (such as CaCl2) or thrombin; wound healing active ingredients such as growth factors; or combinations thereof.

8. The biomimetic dressing-forming composition according to any one of claims 1 to 7, wherein the concentration of the active ingredient in the aqueous phase is 0.1-70 wt%, preferably 5-30 wt%, or more preferably 5-10 wt%.

9. The biomimetic dressing forming composition according to any one of claims 1 to 8, wherein the oil phase and / or the water phase further comprises an antibacterial active ingredient.

10. The biomimetic dressing-forming composition according to claim 9, wherein the antimicrobial active ingredient is selected from triclosan and curcumin.

11. The biomimetic dressing-forming composition according to any one of claims 1 to 10, wherein the concentration of the antimicrobial active ingredient in the oil phase is 0.1-20% by weight, preferably 1-10% by weight, or more preferably 2-7% by weight.

12. The biomimetic dressing-forming composition according to any one of claims 1 to 11, wherein the composition does not contain an emulsifier or a surfactant.

13. The biomimetic dressing-forming composition according to any one of claims 1 to 12, which forms a biomimetic dressing having a double-layer cross-linked structure within 100 seconds, preferably within 80 seconds, 60 seconds, 50 seconds, 40 seconds, 30 seconds, 20 seconds, 10 seconds, 5 seconds or 1 second after photoinitiation.

14. The biomimetic dressing-forming composition according to any one of claims 1 to 13, which is in the form of a liquid preparation. The biomimetic dressing-forming composition according to claim 14 , wherein the liquid preparation is in the form of a spray.

16. The biomimetic dressing-forming composition according to any one of claims 1 to 15, wherein the composition comprises: an oil phase comprising poly(lactic acid-propylene glycol-lactic acid) dimethacrylate and triclosan; An aqueous phase comprising methacrylated gelatin and a water-soluble calcium salt.

17. A biomimetic dressing formed from the biomimetic dressing-forming composition according to any one of claims 1 to 16, the biomimetic dressing comprising at least one double-layer structure having a skin-conforming layer and an outer layer, the outer layer being adjacent to the skin-conforming layer, wherein the skin-conforming layer contacts the skin and comprises a hydrophilic hydrogel, and the outer layer comprises a hydrophobic polymer.

18. The biomimetic dressing according to claim 17, which is formed by the following process: mixing the oil phase and the aqueous phase to form a suspension comprising the oil phase and the aqueous phase, applying the suspension to a surface to form an uncured biomimetic dressing, and The uncured biomimetic dressing is irradiated with light to form the biomimetic dressing.

19. Use of the biomimetic dressing-forming composition according to any one of claims 1 to 16 in preparing a biomimetic dressing.

20. A method of forming a biomimetic dressing, the method comprising Applying a suspension comprising an aqueous phase and an oily phase of the biomimetic dressing-forming composition of any one of claims 1 to 16; and The suspension is cured by photo-initiated polymerization and / or cross-linking to obtain the biomimetic dressing.

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