Bionic skin multilayer composite dressing and preparation method thereof

Abstract

The invention provides a bionic skin multilayer composite dressing and a preparation method thereof, and belongs to the field of medical wound dressings. The invention provides a bionic skin multi-layer composite dressing. The bionic skin multi-layer composite dressing comprises a hydrophobic layer, a hydrogel layer and a hydrophilic fiber layer which are sequentially stacked, the hydrophobic layer is prepared from polymethyl methacrylate and nano silicon dioxide dispersed in the polymethyl methacrylate; the hydrogel layer comprises sodium hyaluronate gel, and recombinant collagen and mussel mucin which are dispersed in the sodium hyaluronate gel. The bionic skin multi-layer composite dressing has good comprehensive performance due to the multi-layer composite structure, the hydrophobic layer, the hydrogel layer and the hydrophilic fiber layer have a synergistic effect, wound healing is effectively promoted, and the hydrophobic layer simulates the barrier function of a cuticle; recombinant collagen in the hydrogel layer can promote epidermis regeneration, mussel mucin forms a nano protective film through dopa groups, and wound adhesion and antibacterial property are enhanced. The hydrophilic fiber layer promotes absorption of wound exudate.

Description

Technical Field

[0001] This invention relates to the field of medical wound dressings, specifically to a biomimetic multilayer composite skin dressing and its preparation method. Background Technology

[0002] In real life, accidents inevitably happen, causing wounds. It is important to treat these wounds promptly to prevent infection. Medical dressings can be applied directly to the wound during treatment.

[0003] Existing dressings have poor moisturizing properties and limited antibacterial and wound-healing functions. Summary of the Invention

[0004] This invention provides a biomimetic multilayer composite dressing and its preparation method. The biomimetic multilayer composite dressing provided by this invention has good moisturizing and antibacterial properties and can effectively promote wound healing.

[0005] This invention provides a biomimetic multilayer composite dressing, comprising a hydrophobic layer, a hydrogel layer, and a hydrophilic fiber layer stacked sequentially. The hydrophobic layer comprises a polymer and nano-silica dispersed in the polymer; the polymer comprises one or more of polymethyl methacrylate, poly(2-hydroxyethyl methacrylate), and polylactic acid-glycolic acid copolymer. The hydrogel layer comprises sodium hyaluronate gel and recombinant collagen and mussel adhesive protein dispersed in the sodium hyaluronate gel.

[0006] Preferably, the mass fraction of the polymer in the hydrophobic layer is 5-15%.

[0007] Preferably, the surface roughness of the hydrophobic layer on the side in contact with the hydrogel layer is 0.08~0.5μm.

[0008] Preferably, the hydrogel layer further includes chitosan, glycerol, carbomer, and ethylparaben dispersed in the sodium hyaluronate gel.

[0009] Preferably, the raw materials for preparing the hydrogel layer, by mass, include 0.3-0.8 parts sodium hyaluronate, 0.2-1 parts recombinant collagen, 0.1-1 parts mussel adhesive protein, 0.5-2 parts chitosan, 5-8 parts glycerol, 0.2-0.5 parts carbomer, 0-0.05 parts ethylparaben, and 90 parts water.

[0010] Preferably, the fibers in the hydrophilic fiber layer include polyvinyl alcohol fibers.

[0011] Preferably, the thickness of the hydrophobic layer is 0.5~2µm; the thickness of the hydrogel layer is 0.04~0.08mm; and the thickness of the hydrophilic fiber layer is 0.1~0.4mm.

[0012] This invention also provides a method for preparing the biomimetic skin multilayer composite dressing described in the above technical solution, comprising the following steps: The hydrophobic layer is obtained by mixing the raw material of the hydrophobic layer with an organic solvent, coating it, and drying it. After coating the surface of the hydrophobic layer with the raw material for preparing the hydrogel layer, a free radical polymerization reaction is carried out to obtain the hydrogel layer. Hydrophilic fibers are mixed with water and then electrospun on the surface of the hydrogel layer to form a hydrophilic fiber layer, thus obtaining the biomimetic skin multilayer composite dressing.

[0013] Preferably, the free radical polymerization reaction is carried out under irradiation with high-energy rays.

[0014] Preferably, the input voltage of the electrospinning is 10~30kV, the receiving distance is 10~30cm, and the propulsion flow rate is 0.1~5mL / h.

[0015] The biomimetic multilayer composite dressing provided by this invention possesses excellent comprehensive performance due to its multilayer composite structure. The hydrophobic layer, hydrogel layer, and hydrophilic fiber layer work synergistically to effectively promote wound healing. Specifically: the hydrophobic layer simulates the barrier function of the stratum corneum; the recombinant collagen in the hydrogel layer promotes epidermal regeneration, and mussel adhesive protein forms a nano-protective film through dopa groups, enhancing wound adhesion and antibacterial properties; the hydrophilic fiber layer promotes the absorption of wound exudate.

[0016] This invention provides a method for preparing the biomimetic skin multilayer composite dressing described above, which optimizes the uniformity of the fiber layer and the retention of bioactivity by adjusting the parameters of electrospinning.

[0017] The biomimetic multilayer skin repair technology of this invention can be widely used in the treatment of various skin injuries, including burns, trauma, and chronic ulcers, and has broad market prospects. Attached Figure Description

[0018] Figure 1 The results of the antibacterial experiment on the dressings in Examples 1 and 2 are as follows; Figure 2 The results of the moisturizing experiment of the dressing in Example 2 are shown. Detailed Implementation

[0019] This invention provides a biomimetic multilayer composite dressing, comprising a hydrophobic layer, a hydrogel layer, and a hydrophilic fiber layer stacked sequentially. The hydrophobic layer comprises polymethyl methacrylate and nano-silica dispersed in the polymethyl methacrylate; The hydrogel layer comprises sodium hyaluronate gel and recombinant collagen and mussel adhesive protein dispersed in the sodium hyaluronate gel.

[0020] The biomimetic skin multilayer composite dressing provided by the present invention includes a hydrophobic layer, the thickness of which is preferably 0.5~2µm, and in specific embodiments of the present invention, it can be 1µm or 1.5µm.

[0021] In this invention, the hydrophobic layer preferably comprises polymethyl methacrylate and nano-silica dispersed in the polymethyl methacrylate; the mass fraction of the polymer in the hydrophobic layer is preferably 5-15%, and in specific embodiments of this invention it can be 8%, 10% or 12%. Polymethyl methacrylate, as a base adhesive, provides good flowability; In this invention, the surface roughness of the hydrophobic layer on the side in contact with the hydrogel layer is preferably 0.08~0.5μm, and in specific embodiments of this invention, it can be 0.1μm, 0.2μm, 0.3μm, or 0.4μm. Nano-silica modifies the surface of the hydrophobic layer, and synergistically with the surface's micro-nano structure, endows the skin's hydrophobic layer with multiple functions such as waterproofing, oil control, moisture permeability, and sustained release of active ingredients.

[0022] The biomimetic skin multilayer composite dressing provided by the present invention includes a hydrogel layer on the surface of a hydrophobic layer; the thickness of the hydrogel layer is preferably 0.04~0.08mm, and in specific embodiments of the present invention it can be 0.05mm, 0.06mm or 0.07mm.

[0023] In this invention, the hydrogel layer comprises sodium hyaluronate gel and recombinant collagen and mussel adhesive protein dispersed within the sodium hyaluronate gel. The recombinant human-like collagen mimics the triple helix structure of human collagen, promoting epidermal regeneration. The mussel adhesive protein forms a nano-protective film through dopa groups, enhancing wound adhesion and antibacterial properties. The sodium hyaluronate gel, in conjunction with the collagen, locks in moisture, repairs the skin barrier, and promotes hydration.

[0024] In this invention, the hydrogel layer preferably further includes chitosan, glycerin, carbomer, and ethylparaben dispersed in the sodium hyaluronate gel. Chitosan has antibacterial properties and promotes wound healing. Glycerin maintains the hydration environment of the dressing. Carbomer regulates the gel consistency and improves its spreadability. The ethylparaben composite preservative system meets the microbial control standards for medical devices.

[0025] The raw materials for preparing the hydrophobic layer preferably include 0.3 to 0.8 parts of sodium hyaluronate by weight, and in specific embodiments of the present invention, they can be 0.4, 0.5, 0.6, or 0.7 parts.

[0026] The raw materials for preparing the hydrophobic layer preferably include 0.2 to 1 part recombinant collagen by mass, and in specific embodiments of the present invention, it can be 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 0.9 parts.

[0027] The raw materials for preparing the hydrophobic layer preferably include 0.1 to 1 part mussel adhesive protein by mass, and in specific embodiments of the present invention, it can be 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 0.9 parts.

[0028] The raw materials for preparing the hydrophobic layer preferably include 0.5 to 2 parts by mass, and in specific embodiments of the present invention, they can be 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, or 1.9 parts.

[0029] The raw materials for preparing the hydrophobic layer preferably include 5 to 8 parts of glycerol by weight, and in specific embodiments of the present invention, they can be 5.5 parts, 6 parts, 6.5 parts, 7 parts or 7.5 parts.

[0030] The raw materials for preparing the hydrophobic layer preferably include 0.2 to 0.5 parts by weight, and in specific embodiments of the present invention, they may be 0.3 or 0.4 parts.

[0031] The raw materials for preparing the hydrophobic layer preferably include 0.01 to 0.05 parts by mass, and in specific embodiments of the present invention, they may be 0.02 parts, 0.03 parts, or 0.04 parts.

[0032] The raw materials for preparing the hydrophobic layer preferably include 90 parts by weight.

[0033] The biomimetic skin multilayer composite dressing provided by the present invention includes a hydrophilic fiber layer on the surface of a hydrogel layer; the thickness of the hydrophilic fiber layer is preferably 0.1~0.4mm, and in specific embodiments of the present invention it can be 0.2mm or 0.3mm.

[0034] In this invention, the fibers preferably include polyvinyl alcohol fibers.

[0035] This invention also provides a method for preparing the biomimetic skin multilayer composite dressing described in the above technical solution, comprising the following steps: The hydrophobic layer is obtained by mixing the raw material of the hydrophobic layer with an organic solvent, coating it, and drying it. After coating the surface of the hydrophobic layer with the raw material for preparing the hydrogel layer, a free radical polymerization reaction is carried out to obtain the hydrogel layer. Hydrophilic fibers are mixed with water and then electrospun on the surface of the hydrogel layer to form a hydrophilic fiber layer, thus obtaining the biomimetic skin multilayer composite dressing.

[0036] The present invention involves mixing the raw materials of the hydrophobic layer with an organic solvent, coating and drying them to obtain the hydrophobic layer.

[0037] In this invention, the organic solvent preferably includes dichloromethane.

[0038] In this invention, the coating is preferably performed by coating the mixture onto a template having a micro / nano structure.

[0039] After obtaining the hydrophobic layer, the present invention coats the surface of the hydrophobic layer with the raw materials for preparing the hydrogel layer and then performs a free radical polymerization reaction to obtain the hydrogel layer.

[0040] In this invention, the free radical polymerization reaction is carried out under the irradiation of high-energy rays, and the temperature of the free radical polymerization reaction is preferably room temperature.

[0041] After obtaining the hydrogel layer, the present invention mixes hydrophilic fibers with water and then electrospins the mixture on the surface of the hydrogel layer to form a hydrophilic fiber layer, thereby obtaining the biomimetic skin multilayer composite dressing.

[0042] In this invention, the input voltage of the electrospinning is preferably 10~30kV, the receiving distance is preferably 10~30cm, and the propulsion flow rate is preferably 0.1~5mL / h. In specific embodiments of this invention, the input voltage can be 15kV, 20kV, or 25kV, the receiving distance can be 15cm, 20cm, or 25cm, and the propulsion flow rate can be 1mL / h, 2mL / h, 3mL / h, or 4mL / h.

[0043] The following detailed description of the biomimetic multilayer composite dressing and its preparation method provided by the present invention, with reference to the embodiments, should not be construed as limiting the scope of protection of the present invention.

[0044] Example 1 A: Preparation of hydrophobic layer: 5g of polymethyl methacrylate was dissolved in 50mL of dichloromethane, an organic solvent. 3g of nano-sized silica particles were added and stirred until homogeneous. The mixture was then spin-coated onto a template to form a thin film, which was then dried. The template was then removed to obtain a hydrophobic layer with a thickness of 1μm and a roughness of 0.5μm (the template contained several cylinders with a diameter of 100nm and a contact angle of 165.2°).

[0045] B: Preparation of hydrogel layer: 1g of recombinant human collagen, 0.5g of mussel adhesive protein, 8g of glycerol, 0.01g of ethylparaben, and 90mL of sterile water were mixed to form an aqueous solution. Then, 0.3g of low molecular weight sodium hyaluronate, 0.6g of chitosan, and 0.3g of carbomer were slowly added and coated onto the hydrophobic layer. The polymer chain free radical crosslinking was directly induced by γ-rays for 7min to form a hydrogel layer with a thickness of 0.04mm.

[0046] C: Preparation of the hydrophilic fiber layer: 25g of polyvinyl alcohol powder was dissolved in 250mL of sterile water to form a polyvinyl alcohol solution. The hydrophilic polymer material, polyvinyl alcohol solution, was spun into fibers using high-voltage electrospinning technology and collected on the hydrogel layer to form a 0.2mm thick hydrophilic fiber layer. Electrospinning parameters: input voltage 20kV, receiving distance 20cm, and feed rate 1mL / h.

[0047] (1) Transdermal release test: Transdermal test was conducted using pig skin to test the release rate of subcutaneous gel after 24 hours. Data from 0h, 3h, 6h, 12h, and 24h showed that the release rate was directly proportional to time, proving that the gel has good release activity.

[0048] Stability test: After 24 hours of cold resistance test at -20℃ and heat resistance test at 40℃, there was no significant change after returning to room temperature.

[0049] (2) Intradermal irritation test in rabbits: In accordance with GB / T16886.10-2017 Biological evaluation of medical devices - Part 10: Stimulation and delayed-type hypersensitivity test, an intradermal reaction test was conducted. The humanoid biomimetic functional dressing extract (using 0.9% NaCl solution (physiological saline), mixed at a ratio of 0.2 g / mL of dressing to 0.9% NaCl solution and extracted at 37℃ for 72 h) was administered intradermally, with the same batch of physiological saline as the control group. Specifically, the left side of the rabbit's back was treated with the extract, and the right side with physiological saline. The potential for the material to produce a stimulating reaction under the test conditions was evaluated after 0 h, 24 h, 48 h, and 72 h. The final score of the test sample was 0 points, with no erythema or edema, indicating good biocompatibility of the product.

[0050] (3) In vitro cytotoxicity test: The MTT assay was performed in accordance with GB / T16886.5-2017 Biological evaluation of medical devices Part 5: In vitro cytotoxicity test. There was no cell lysis, no decrease in cell proliferation, and the morphology of surrounding cells was normal. The survival rate reached 99%, indicating no cytotoxicity.

[0051] Example 2 A: Preparation of hydrophobic layer: Same as in Example 1.

[0052] B: Preparation of hydrogel layer: Prepared in two groups.

[0053] Group 1: Same as Example 1.

[0054] Group 2: 1g of recombinant human collagen, 0.5g of mussel adhesive protein, and 90mL of sterile water were mixed to form an aqueous solution. Then, 0.3g of low molecular weight sodium hyaluronate, 0.6g of chitosan, and 0.3g of carbomer were slowly added. This solution was coated onto a hydrophobic layer, and the polymer chains were directly induced to cross-link using gamma rays for 7 minutes to form a hydrogel layer with a thickness of 0.04mm. Ethylparaben was not added.

[0055] C: Preparation of hydrophilic fiber layer: Same as in Example 1.

[0056] (1) Antibacterial experiment study: The antibacterial efficacy test was conducted in accordance with the 2025 edition of the Chinese Pharmacopoeia, Part IV, 1121. The two groups were compared, and the results proved that the dressing applied for this time has a very good antibacterial effect.

[0057] Figure 1 The results of the antibacterial experiments on the dressings in Examples 1 and 2 are shown. Figure 1 The left image shows the dressing of Example 1, and the right image shows the dressing of Example 2.

[0058] Depend on Figure 1 It can be seen that the dressing in Example 1 has a good antibacterial effect and can effectively inhibit the growth of Staphylococcus aureus.

[0059] (2) Moisturizing effect test: Take an appropriate amount of this product and divide it into 6 groups. The treatment time is 0h, 4h, 8h, 12h, 24h and 48h respectively. The moisture content is measured by a moisture meter. The results are as follows: Figure 1 As shown.

[0060] Figure 2 The results of the moisturizing experiment of the dressing in Example 2 are shown.

[0061] Depend on Figure 2 It can be seen that the moisture content of the dressing remained within a high range after 24 hours of application, indicating that it has excellent moisturizing properties.

[0062] Example 3 The only difference from Example 1 is that polymethyl methacrylate is replaced with poly(2-hydroxyethyl methacrylate).

[0063] The mechanical strength of the dressing is weaker than that of the dressing in Example 1.

[0064] Example 4 The only difference from Example 1 is that polymethyl methacrylate is replaced with PLGA (polylactic acid-glycolic acid copolymer).

[0065] The hydrophobicity of the dressing is weaker than that of the dressing in Example 1.

[0066] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A biomimetic multilayer composite dressing, characterized in that, It consists of a hydrophobic layer, a hydrogel layer, and a hydrophilic fiber layer stacked sequentially; The hydrophobic layer comprises a polymer and nano-silica dispersed in the polymer; the polymer comprises one or more of polymethyl methacrylate, poly(2-hydroxyethyl methacrylate), and polylactic acid-glycolic acid copolymer. The hydrogel layer comprises sodium hyaluronate gel and recombinant collagen and mussel adhesive protein dispersed in the sodium hyaluronate gel.

2. The biomimetic skin multilayer composite dressing according to claim 1, characterized in that, The mass fraction of the polymer in the hydrophobic layer is 5-15%.

3. The biomimetic skin multilayer composite dressing according to claim 1, characterized in that, The surface roughness of the hydrophobic layer on the side in contact with the hydrogel layer is 0.08~0.5μm.

4. The biomimetic skin multilayer composite dressing according to claim 3, characterized in that, The hydrogel layer also includes chitosan, glycerol, carbomer, and ethylparaben dispersed in the sodium hyaluronate gel.

5. The biomimetic skin multilayer composite dressing according to claim 4, characterized in that, The raw materials for preparing the hydrogel layer, by mass, include 0.3-0.8 parts sodium hyaluronate, 0.2-1 parts recombinant collagen, 0.1-1 parts mussel adhesive protein, 0.5-2 parts chitosan, 5-8 parts glycerol, 0.2-0.5 parts carbomer, 0-0.05 parts ethylparaben, and 90 parts water.

6. The biomimetic skin multilayer composite dressing according to claim 1, characterized in that, The fibers in the hydrophilic fiber layer include polyvinyl alcohol fibers.

7. The biomimetic skin multilayer composite dressing according to claim 1, characterized in that, The thickness of the hydrophobic layer is 0.5~2µm; the thickness of the hydrogel layer is 0.04~0.08mm; and the thickness of the hydrophilic fiber layer is 0.1~0.4mm.

8. A method for preparing the biomimetic skin multilayer composite dressing according to any one of claims 1 to 7, characterized in that, Includes the following steps: The hydrophobic layer is obtained by mixing the raw material of the hydrophobic layer with an organic solvent, coating it, and drying it. After coating the surface of the hydrophobic layer with the raw material for preparing the hydrogel layer, a free radical polymerization reaction is carried out to obtain the hydrogel layer. Hydrophilic fibers are mixed with water and then electrospun on the surface of the hydrogel layer to form a hydrophilic fiber layer, thus obtaining the biomimetic skin multilayer composite dressing.

9. The preparation method according to claim 8, characterized in that, The free radical polymerization reaction is carried out under the irradiation of high-energy rays.

10. The preparation method according to claim 8, characterized in that, The input voltage for electrospinning is 10~30kV, the receiving distance is 10~30cm, and the propulsion flow rate is 0.1~5mL / h.

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