A dressing for skin defect wound repair and its preparation method and application

Abstract

The application discloses a dressing for skin defect wound repair and a preparation method and application thereof, and belongs to the field of dressing application materials. The dressing prepared by the application is a film embedding cerium phosphate nanorods and loaded polyphenol drugs, and the method comprises the following steps: uniformly dispersing a certain proportion of prepared cerium phosphate and drugs in anhydrous ethanol by using ultrasonic waves, then adding a polymer polyvinylpyrrolidone to completely dissolve, adding the prepared precursor solution into a used electrospinning device or a spray gun, and adjusting parameters in the process to make the dressing deposit in situ at a wound. Since the material has good hydrophilicity, can quickly absorb wound exudates, has good biocompatibility and active oxygen scavenging capacity, can adapt to the needs of irregular wounds, and is suitable for treating acute full-thickness skin defect wounds or chronic inflammatory skin wounds caused by diabetes and the like.

Description

Technical Field

[0001] This invention belongs to the field of biomedical dressing technology, specifically relating to a dressing for repairing skin defects and wounds, its preparation method, and its application. Background Technology

[0002] As the largest organ in the human body, the skin is the first line of defense against external pathogens, chemical irritants, and physical damage. It also plays a vital role in regulating body temperature, maintaining hydration, and sensing the external environment. Its repair process involves multiple coordinated steps, including inflammation regulation, angiogenesis, fibroblast proliferation and differentiation, and collagen remodeling, and is easily affected by factors such as oxidative stress, infection, and local microcirculatory disturbances. In special populations such as diabetic patients and the elderly, delayed healing, hypertrophic scarring, and even non-healing wounds are common, significantly increasing the difficulty of treatment and seriously impacting patients' health and quality of life. Promoting rapid and effective wound healing is a key goal of clinical nursing.

[0003] While commonly used clinical dressings (such as gauze and foam dressings) can provide moisture and isolation, they cannot simultaneously address the core issues of oxidative stress damage, inflammatory imbalance, and insufficient tissue regeneration in wounds, thus failing to effectively accelerate the functional repair of damaged tissues. Therefore, developing novel biomaterials with antioxidant, anti-inflammatory, and tissue-regenerating functions, and constructing a treatment system adapted to the microenvironment of skin defect repair, has become a key research direction for improving wound healing quality and reducing the clinical burden.

[0004] Compared to traditional dressings, cerium phosphate nanorods can mimic the properties of biological enzymes and intelligently regulate the wound microenvironment. Furthermore, the electrospun dressings can form nano- to micron-sized fiber membranes through electrostatic interaction. Their three-dimensional porous structure is highly similar to the collagen fiber network of the skin's dermis, providing a scaffold for wound cells to guide orderly cell migration and efficiently absorbing wound exudate, maintaining a moist local environment. Chinese patent CN120242119A discloses a COF electrospun wound dressing with near-infrared response and antioxidant activity, characterized in that the spinning solution is a 20wt% polycaprolactone solution in dichloromethane. Chinese patent CN120459350A discloses a polyhydroxyalkanoate electrospun wound dressing, wherein the organic solvent in the PHA mixed solution includes one of hexafluoroisopropanol, dichloromethane, and dimethylacetamide. The electrospinning solvents used in the electrospinning of the aforementioned prepared electrospinning dressings are solutions with toxic and irritating odors, such as dichloromethane, chloroform, and acetone. For example, dichloromethane may cause dry skin, redness, and stinging, and in severe cases, chemical burns or dermatitis. Compared to the in-situ preparation method in electrospinning mentioned above, conventional dressings need to be prepared in designated equipment and then fixed to the wound using medical adhesives. Summary of the Invention

[0005] To address the challenges of complex manufacturing processes and the susceptibility of prepared wound dressings to environmental factors that can lead to component degradation or reduced activity during storage and transportation, this invention provides a dressing for repairing skin defects and its preparation method. This dressing better meets the personalized repair needs of skin wounds, offering improvements in adaptability, safety, and functionality. To achieve the aforementioned objectives, this invention utilizes the following technical solution: a dressing for repairing skin defects, comprising 8%-14wt% polymer, 0.1%-4wt% functional materials, and 0.1%-1wt% functional drugs.

[0006] The prepared repair solution is added to the device and electrospinned, sprayed, or dripped onto the wound to obtain a dressing for repairing skin defects: the repair solution is a mixture of functional materials, functional drugs, and polymer solutions.

[0007] A method for preparing a dressing for repairing skin defects and wounds includes: using cerium phosphate nanorods in a cerium phosphate hydrogel dialyzed with a dialysis solution containing hydrochloric acid or nitric acid as a functional material; adding one or more natural polyphenolic compounds with antioxidant, anti-inflammatory, and antibacterial activities; and finally adding a polymeric material that is both biocompatible and processable to obtain a dressing for repairing skin defects and wounds.

[0008] Preferably, the functional material is cerium phosphate nanorods in a cerium phosphate hydrogel after dialysis for 72 hours with a dialysis solution containing hydrochloric acid and nitric acid at pH 2-3. The polymer includes biocompatible and processable high-molecular materials such as polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl butyral, and chitosan. The functional drug includes one or more natural polyphenolic compounds with antioxidant, anti-inflammatory, and antibacterial activities, such as epigallocatechin gallate, gallic acid, rutin, and curcumin.

[0009] Preferably, the electrospinning preparation method uses the following process parameters: spinning voltage 10-20KV, temperature 10-40℃, relative humidity 30-70%, and receiving distance 10-25cm. Preferably, the electrospinning syringe is a 5ml medical syringe with a 20-24G flat-head metal needle. Preferably, the spraying preparation method uses the following process parameters: spraying pressure 0.1-0.5MPa, spraying distance 5-30cm, spraying rate 0.5-2ml / min (uniform sweeping), atomized particle size 50μm-100μm, and spraying angle 30°-90°. The dripping preparation method uses the following process parameters: dripping speed 1 drop / 3-6 seconds. Preferably, the in-situ preparation in the electrospinning preparation method uses a handheld electrospinning gun, an in-situ coating machine, or a fixed in-situ electrospinning device. The dressings prepared by any of the above methods are used in the treatment of trauma, burns, scalds, chronic diabetic wounds, and infected ulcers with exudate.

[0010] The beneficial effects of the present invention are as follows: A hydrophilic dressing can be prepared by the above method; it can perfectly fit irregular wounds; it can quickly absorb exudate and keep the wound moist for a long time; cerium phosphate nanorods and polyphenolic drugs have antibacterial and antioxidant effects, which can assist wound healing and synergistically fight bacteria. Anhydrous ethanol is used as a solvent in this method. Ethanol is volatile and non-toxic, and there are no toxic solvent residues. Attached Figure Description

[0011] Figure 1 is a scanning electron microscope (SEM) image of the electrospun fibers prepared in Example 1 of this invention.

[0012] Figure 2 shows the transmission electron microscope (TEM) image of the cerium phosphate nanorods in Example 1 of this invention, the dark field TEM image of the electrospun fiber membrane, and the elemental analysis diagram.

[0013] Figure 3 shows the XRD pattern, FTIR pattern, and TG-DSC pattern of the electrospun fiber membrane in Example 1.

[0014] Figure 4 shows the dark-field transmission electron microscope images of the electrospun fiber membranes in Examples 2 and 3.

[0015] Figure 5(a) is a schematic diagram of spraying in Example 4, and Figure 5(b) is a morphological image taken by transmission electron microscopy after drop-in in Example 5.

[0016] Figure 6 shows the test results of the DPPH method and PTIO method in Test Example 1.

[0017] Figure 7 shows the results of the hemolysis and cytotoxicity tests in Test Example 2.

[0018] Figure 8 is a schematic diagram of the experimental procedure for Test Example 3.

[0019] Figure 9 shows representative images and dynamic simulation diagrams of wound recovery on days 0, 3, 7, 10, and 14 for different experimental materials in Test Example 3.

[0020] Figure 10 shows the calculated wound healing rate of different experimental material groups in Test Example 3. Detailed Implementation

[0021] The present invention will be further described below with reference to specific embodiments and accompanying drawings. Those skilled in the art will be able to implement the present invention based on these descriptions, but the embodiments of the present invention are not limited thereto.

[0022] Unless otherwise specified, all reagents used in the examples are commercially available.

[0023] PVP was purchased from Shanghai Maclean Biotechnology Co., Ltd., and epigallocatechin gallate (EGCG) was purchased from Beijing Solarbio Technology Co., Ltd. Example

[0024] Step 1: Weigh 1.3g of cerium nitrate hexahydrate (molecular weight 434.22, 0.003mol) and add it to 10 mL of deionized water. Stir magnetically until dissolved. Add 200μL of phosphoric acid (0.003mol) and 0.36mL of ammonia to 10 mL of deionized water and mix. At room temperature, under vigorous stirring, slowly add the latter to the former, continuing stirring for 24 hours. Step 2: After the reaction is complete, the reactants are centrifuged and added to a dialysis bag (MD-30000 Da). The solution outside the dialysis bag is hydrochloric acid solution with a pH of 2. Dialysis is performed under magnetic stirring for 3 days, with the solution changed every 6 hours until the dialysis is completed. After dialysis, the liquid in the bag is centrifuged, and the precipitate after centrifugation is used to obtain purified cerium phosphate (CePO4) nanorods. Step 3: Take 175.9 mg CePO4 and add it to 10 mL of anhydrous ethanol. Sonicate for 20 min and then magnetically stir (500 r / min, 2 h) until it is evenly dispersed. Weigh 17.6 mg EGCG and stir again for 30 min. Weigh 0.71 g PVP (MW: 1300000) and add it to the solution of the well dispersed functional material and drug. Stir for 24 h to obtain a well mixed precursor solution with a polymer solute mass of 8 wt%, CePO4 of 2 wt%, and EGCG of 0.2 wt%.

[0025] Step 4: After sonicating the electrospinning precursor solution prepared in Step 3 for 10 minutes, let it stand for 20 minutes to defoam, then add... A 5ml syringe with a 22G needle was inserted into the spinning equipment. The switch was turned on, the injector position was adjusted, the voltage was set to 15KV, the room temperature to 25℃, and the relative humidity to 40%. The voltage switch was then turned on, ensuring a vertical distance of 15cm between the needle nozzle of the spinning syringe and the wound, thus forming an electrospun fiber membrane dressing. Its morphology is shown in Figure 1.

[0026] Figure 1 is a scanning electron microscope image of the electrospun fiber membrane in Example 1, showing that the fiber size in the prepared fiber membrane is uniform.

[0027] Figure 2 shows the transmission electron microscope (TEM) image of the cerium phosphate nanorods in Example 1, the dark field TEM image and elemental analysis diagram of the electrospun fiber membrane. It can be seen that the cerium phosphate nanorods in the prepared fiber membrane are axially aligned in the fiber under the action of electrostatic force.

[0028] Figure 3 shows the XRD, FTIR, and TG-DSC patterns of the electrospun fiber membrane in Example 1. It can be seen that the prepared fiber membrane does indeed contain cerium phosphate nanorods, and the thermal stability of the fiber membrane is relatively good. Example

[0029] Steps 1 and 2 are the same as in Example 1; Step 3: Take 87 mg CePO4 and add it to 10 mL of anhydrous ethanol. Sonicate for 20 min and then magnetically stir (500 r / min, 2 h) until it is evenly dispersed. Weigh 17.4 mg EGCG and stir again for 30 min. Weigh 0.70 g PVP (MW: 1300000) and add it to the solution of the well dispersed functional material and drug. Stir for 24 h to obtain a well mixed precursor solution with a polymer solute mass of 8 wt%, CePO4 of 1 wt%, and EGCG of 0.2 wt%.

[0030] Step 4: After sonicating the precursor solution prepared in Step 3 for 10 minutes, let it stand for 20 minutes to defoam, add it to a 5ml syringe, select a needle specification of 22G, install it into the spinning equipment, turn on the switch, adjust the position of the injector, adjust the voltage to 15KV, room temperature 25℃, relative humidity 40%, turn on the voltage switch, and make the vertical distance between the injection nozzle of the spinning syringe needle and the wound 15cm to form an electrospun fiber membrane dressing.

[0031] Figure 4(a) is a dark-field transmission electron microscope image of the electrospun fiber membrane in Example 2; Example

[0032] Steps 1 and 2 are the same as in Example 1; Step 3: Take 266.9 mg CePO4 and add it to 10 mL of anhydrous ethanol. Sonicate for 20 min and then magnetically stir (500 r / min, 2 h) until it is evenly dispersed. Weigh 17.8 mg EGCG and stir again for 30 min. Weigh 0.72 g PVP (MW: 1300000) and add it to the solution of the well dispersed functional material and drug. Stir for 24 h to obtain a well mixed precursor solution with a polymer solute mass of 8 wt%, CePO4 of 3 wt%, and EGCG of 0.2 wt%.

[0033] Step 4: After sonicating the precursor solution prepared in Step 3 for 10 minutes, let it stand for 20 minutes to defoam, add it to a 5ml syringe, select a needle specification of 22G, install it into the spinning equipment, turn on the switch, adjust the position of the injector, adjust the voltage to 15KV, room temperature 25℃, relative humidity 40%, turn on the voltage switch, and make the vertical distance between the injection nozzle of the spinning syringe needle and the wound 15cm to form an electrospun fiber membrane dressing.

[0034] Figure 4(b) is a dark-field transmission electron microscope image of the electrospun fiber membrane in Example 3; Example 4 Steps 1, 2, and 3 are the same as in Example 1; Step 4: Fill the reservoir of the sterile spray gun with the solution prepared in Step 3. Aim at the cleaned wound surface and spray at a distance of 10 cm, using a spray pressure of 0.3 MPa (30 psi) and a constant speed of 1 mL / min. The solution will evenly coat the wound surface in aerosol form, forming a transparent, breathable biomimetic barrier film that closely conforms to the wound contour.

[0035] Figure 5(a) is a schematic diagram of spraying in Example 4.

[0036] Example

[0037] Steps 1, 2, and 3 are the same as in Example 1; Step 4: Using a sterile pipette or syringe, draw an appropriate amount of the prepared solution. Hold the pipette tip close to, but not touching, the wound surface, and continuously, slowly, and evenly add the solution drop by drop at a rate of 1 drop per 5 seconds until the wound area is completely covered. Due to its rheological properties, the solution spontaneously levels and fills the irregular depressions on the wound surface. Under alkaline conditions in the wound area, the solution transforms from a sol to a gel, forming a transparent, seamless protective film that closely adheres to the wound contour.

[0038] Figure 5(b) is a transmission electron microscope image of the morphology after the addition of the sample in Example 5.

[0039] Example

[0040] Steps 1 and 2 are the same as in Example 1; Step 3: Weigh 90.0 mg CePO4 and add it to 10 mL of anhydrous ethanol. Sonicate for 20 min and then magnetically stir (500 r / min, 2 h) until evenly dispersed. Then weigh 45.0 mg curcumin and 45.0 mg rutin (mass ratio 1:1) and add them to the above dispersion. Continue stirring at 500 r / min for 30 min. Then add 450.0 mg PVP (MW: 1300000) and 450.0 mg PVB (mass ratio 1:1) in batches (1 / 3 of the mass added each time, 5 min apart). Continue stirring at 500 r / min for 24 h. Finally, a precursor solution with 10 mL of ethanol as solvent is obtained, in which the total mass fraction of PVP-PVB is 10 wt%, the mass fraction of CePO4 is 1 wt%, and the total mass fraction of curcumin-rutin is 1 wt%. The solution is pale yellow and transparent. After sealing, store in a cool, dark place for later use.

[0041] Step 4: After sonicating the electrospinning precursor solution prepared in Step 3 for 10 minutes, let it stand for 20 minutes to defoam, add it to a 5ml syringe, select a 22G needle, install it into the spinning equipment, turn on the switch, adjust the position of the injector, adjust the voltage to 15KV, room temperature 25℃, relative humidity 40%, turn on the voltage switch, and make the vertical distance between the injection nozzle of the spinning syringe needle and the wound 15cm to form a PVP-PVB electrospinned fiber membrane dressing. Example

[0042] Steps 1 and 2 are the same as in Example 1; Step 3: Weigh 43.8 mg CePO4 and add it to 10 mL of anhydrous ethanol. Sonicate for 20 min and then stir magnetically (500 r / min).

[0043] (2 hours) until uniformly dispersed; then weigh 8.8 mg EGCG and add it to the above dispersion, stirring continuously at 500 r / min. Add 0.9894 g PVP (MW: 1300000) and stir continuously at 500 r / min for 24 h to finally obtain a precursor solution with 10 mL of ethanol as solvent, wherein the mass fraction of PVP is 14 wt%, the mass fraction of CePO4 is 0.5 wt%, and the mass fraction of EGCG is 0.1 wt%.

[0044] Comparative Example 1 Step 1: Weigh 0.69g PVP (MW: 1300000) and add it to 10mL of anhydrous ethanol solution. Stir magnetically (500r / min) for 24h to obtain a homogeneous polymer spinning solution of 8wt.

[0045] Step 2: After sonicating the precursor solution prepared in Step 1 for 10 minutes, let it stand for 20 minutes to defoam, add it to a 5ml syringe, select a needle specification of 22G, install it in the spinning equipment, turn on the switch, adjust the position of the injector, adjust the voltage to 15KV, room temperature 25℃, relative humidity 40%, turn on the voltage switch, and make the vertical distance between the injection nozzle of the spinning syringe needle and the wound 15cm to obtain the control group (comparative example 1) which contains no functional materials or functional drugs, but only the base organic material.

[0046] Comparative Example 2 Step 1: Take 175.5 mg CePO4 and add it to 10 mL of anhydrous ethanol. Sonicate for 20 min and then stir magnetically (500 r / min, 2 h) until it is evenly dispersed. Weigh 0.71 g PVP (MW: 1300000) and add it to the solution of the well dispersed functional material and drug. Stir for 24 h to obtain a well mixed polymer solute with a mass of 8 wt% and CePO4 as a 2 wt% precursor solution.

[0047] Step 2: After sonicating the precursor solution prepared in Step 1 for 10 minutes, let it stand for 20 minutes to defoam, add it to a 5ml syringe, select a needle specification of 22G, install it in the spinning equipment, turn on the switch, adjust the position of the injector, adjust the voltage to 15KV, room temperature 25℃, relative humidity 40%, turn on the voltage switch, and make the vertical distance between the injection nozzle of the spinning syringe needle and the wound 15cm to obtain the control group (comparative example 2) containing only functional materials and no functional drugs.

[0048] Comparative Example 3 Step 1: Weigh 17.2 mg of EGCG and stir magnetically (500 r / min) for 30 min. Weigh 0.69 g of PVP (MW: 1300000) and add it to the well-dispersed functional drug solution. Stir for 24 h to obtain a well-mixed precursor solution with a polymer solute mass of 8 wt% and EGCG of 0.2 wt%.

[0049] Step 2: After sonicating the electrospinning precursor solution prepared in Step 1 for 10 minutes, let it stand for 20 minutes to defoam, add it to a 5ml syringe, select a needle specification of 22G, install it in the spinning equipment, turn on the switch, adjust the position of the injector, adjust the voltage to 15KV, room temperature 25℃, relative humidity 40%, turn on the voltage switch, and make the vertical distance between the injection nozzle of the spinning syringe needle and the wound 15cm to obtain the control group comparative example 3 containing only functional drugs.

[0050] Test Example 1 To investigate the material's effect on wound healing, its ability to scavenge reactive oxygen species was tested using the DPPH and PTIO methods. As shown in Figure 6, the prepared electrospun fiber membrane possesses the ability to scavenge reactive oxygen species.

[0051] Test Example 2 To investigate the biocompatibility of the material, the safety of the material was tested using a hemolysis test and the MTT assay (L929 cells).

[0052] As shown in Figure 7, the prepared fibrous membrane has a low hemolysis rate (<2%) and does not cause cytotoxicity.

[0053] Test Example 3 To investigate the effect of the material on wound healing, this invention used 6-8 week old female Balb / C mice. After anesthesia with 1.25% tribromoethanol, the back hair was removed to fully expose the skin. The backs of the mice, the skin biopsy instrument, and surgical instruments were disinfected with povidone-iodine. A 6mm full-thickness skin defect was created on the back of the mice using a 6mm skin biopsy instrument. The mice were randomly divided into four groups: a control group (no treatment), a comparative group 1 (in-situ deposition of 8wt% PVP fibers without other materials), a comparative group 2 (in-situ deposition of fibers containing only functional materials but no drugs), a comparative group 3 (in-situ deposition of fibers containing only functional drugs), and Example 1 (in-situ deposition of fibers containing 2wt% functional materials, 0.2wt% functional drugs, and 8wt% polymers as per the Example 1 formulation). Wound healing was observed and photographed on days 0, 3, 7, 10, and 14. The wound healing rate of different groups was calculated (see Figure 9). Histological analysis was performed on wounds healed for 14 days. The healing effect of Example 1 group was the best after 14 days, with a healing rate of 100%.

[0054] As shown in Figures 8-10, the electrospun fiber membrane in Example 1 has a good ability to promote wound healing.

[0055] The specific embodiments described herein are merely illustrative of the spirit of the invention. Those skilled in the art to which this invention pertains may make various modifications or additions to the described specific embodiments or use similar methods to substitute them, without departing from the spirit of the invention or exceeding the scope defined by the appended claims.

Claims

1. A method for preparing a dressing for repairing skin defects and wounds, characterized in that, Includes the following steps: S1: Provide cerium phosphate nanorods in cerium phosphate hydrogel after 72 hours of dialyzing with a dialysis solution containing hydrochloric acid or nitric acid at pH 2-3 as a functional material; S2: Disperse the cerium phosphate nanorods obtained in step S1 in anhydrous ethanol, and then add one or more natural polyphenolic compounds selected from epigallocatechin gallate (EGCG), gallic acid, rutin, and curcumin as functional drugs, and stir until homogeneous. S3: Add one or more polymers selected from polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl butyral, and chitosan to the dispersion obtained in step S2, and stir until completely dissolved to form a precursor solution; wherein, in the precursor solution, the polymer mass concentration is 8% or 10%, and the solution contains 2wt% CePO4 and 0.2wt% EGCG, or 1wt% CePO4 and 0.2wt% EGCG, or 3wt% CePO4 and 0.2wt% EGCG, or 0.5wt% CePO4 and 0.1wt% EGCG, or 1wt% CePO4 and 1wt% curcumin-rutin. S4: The precursor solution obtained in step S3 is electrospun to form a dressing in situ at the wound site. The electrospinning parameters are as follows: a 5mL syringe and a 20-24G flat-headed metal needle are used; the spinning voltage is 10-20KV; the temperature is 10-40℃; the relative humidity is 30-70%; and the receiving distance is 10-25cm.

2. The preparation method according to claim 1, characterized in that, The polymer is polyvinylpyrrolidone.

3. The preparation method according to claim 1, characterized in that, The functional drug is epigallocatechin gallate.

4. The preparation method according to claim 1, characterized in that, In step S4, the dressing formed by electrospinning is a nanofiber membrane.

5. A dressing for repairing skin defects and wounds, characterized in that, Prepared by the method according to any one of claims 1-4.

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