A pH-responsive dual-drug-loaded bionic wound dressing and its preparation method

Abstract

The present invention relates to a pH-responsive dual-drug bionic wound dressing and a preparation method thereof, comprising: a barrier layer, which is a polycaprolactone / glacial acetic acid solution, electrospun on one side of a hemostatic layer; a hemostatic layer, which is a gelatin sponge, located between the barrier layer and the antibacterial layer; an antibacterial layer, comprising an antibacterial drug and a first carrier, electrospun on the other side of the hemostatic layer, the first carrier dissolving when pH>7, and releasing the antibacterial drug; an anti-inflammatory layer, comprising an anti-inflammatory drug and a second carrier, electrospun on one side of the antibacterial layer, the second carrier dissolving when pH is 1-5, and releasing the anti-inflammatory drug. In the present invention, the antibacterial layer and the anti-inflammatory layer can release drugs on demand during different pH periods of wound infection, avoiding drug abuse or toxic effects on cells. The wound dressing preparation method disclosed at the same time has simple process steps, high efficiency, and low cost, so that this four-layer pH-responsive dual-drug bionic wound dressing has extremely high application and promotion value in commercial production and clinical applications.

Description

Technical Field

[0001] The present invention relates to the technical field of wound repair, and in particular to a pH-responsive dual-drug-loaded bionic wound dressing and a preparation method thereof. Background Art

[0002] The skin is the largest organ in the human body and serves a vital role as a barrier. It effectively prevents the loss of water, electrolytes, and other substances in the body, and protects against the intrusion of harmful substances from the external environment. The skin has a three-layer structure: the epidermis, dermis, and subcutaneous tissue. The epidermis, the outermost layer of the skin, is composed of numerous keratinocytes and a small number of melanocytes and Langerhans cells, with an average thickness of 0.2 mm. The dermis is composed of fibroblasts and contains numerous skin appendages such as hair follicles, sweat glands, and blood vessels. The subcutaneous tissue is composed of fat and collagen cells.

[0003] When skin is injured, the body triggers a complex healing process to repair the damaged tissue. Normal skin wound healing involves four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. During the hemostasis phase of wound healing, a neural reflex triggers contraction of vascular smooth muscle cells, causing the damaged blood vessels to rapidly constrict, thus initiating hemostasis. Subsequently, platelets aggregate at the wound site to form a blood clot, effectively stopping bleeding. Finally, platelets rupture and release growth factors, attracting neutrophils, macrophages, and fibroblasts, which play a crucial role in the subsequent healing phase. The inflammatory phase protects the wound from microbial infection by forming an immune barrier. The early inflammatory phase occurs 24 to 36 hours after skin injury, with neutrophils phagocytizing microorganisms and foreign matter before being expelled to the wound surface and engulfed by macrophages. The late inflammatory phase occurs 36 to 72 hours after skin injury, with macrophages phagocytizing microorganisms, necrotic tissue, and debris, secreting large amounts of growth factors and tumor necrosis factor, amplifying inflammation, defending against exogenous bacteria, and initiating the proliferation phase. The proliferative phase primarily involves the formation of granulation tissue, angiogenesis, and re-epithelialization. At the end of the proliferative phase, wound fibroblasts differentiate into myofibroblasts, which promote wound contraction. The remodeling phase is the final stage of wound healing, during which the type III collagen that forms the granulation tissue is replaced by type I collagen, the primary component of the dermis.

[0004] Wounds can be divided into two categories based on how long they take to heal: acute wounds (such as cuts, abrasions, and contusions) and chronic wounds (such as diabetic ulcers and bedsores). Skin wound healing is a very efficient process. However, local factors such as insufficient blood supply, bacterial infection, and oxidative stress, as well as systemic factors such as age, psychological stress, and diabetes, can affect the wound healing process, resulting in chronic or non-healing wounds that require long-term and expensive treatment and severely reduce the patient's quality of life.

[0005] The use of wound dressings is essential for the healing of chronic wounds. The more layers a wound dressing has, the more bioactive it can be, meeting the needs of different wound healing stages. The synergistic effect of multiple functional layers can further promote wound healing. Current wound dressings, such as gauze, sterile cotton balls, and hydrophilic gels, are widely used, but these strategies have several drawbacks. For example, gauze and sterile cotton balls can provide a physical barrier to wounds, but their high absorption of wound tissue fluid can easily lead to wound dehydration, hindering wound healing. They can also cause secondary damage to newly formed skin during replacement. Hydrophilic gels can provide a moist environment for wound healing, and their structure facilitates gas exchange and exudate absorption within the wound. However, hydrogels are soft, fragile, and complex to prepare. An ideal wound dressing should possess several key properties, including providing a suitable moist environment for the wound, appropriate mechanical properties, a structure and composition similar to normal skin, biocompatibility, and effective anti-infective and anti-inflammatory capabilities. These complex functionalities are difficult to achieve with conventional wound dressings.

[0006] Chronic skin wounds are often associated with bacterial infection. When bacterial infection occurs at the site of a skin wound, the pH level of the wound changes significantly. Furthermore, persistent inflammation can lead to a severe imbalance between oxidation and antioxidant activity in the body, causing cytotoxicity and even tissue damage. Therefore, to effectively promote wound healing, it is necessary not only to prevent bacterial infection but also to eliminate excessive inflammation.

[0007] However, during the wound healing process, the dynamic changes in the release of drugs from wound dressings into the wound may lead to drug abuse and even toxic effects on cells, adversely affecting wound healing. Therefore, how to achieve on-demand drug release has become a pressing issue for those skilled in the art. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art and provide a pH-responsive dual-drug loaded bionic wound dressing and a preparation method thereof, which can realize on-demand release of drugs and achieve efficient repair.

[0009] The present invention is achieved through the following technical solutions:

[0010] A pH-responsive dual-drug-loaded bionic wound dressing comprises a barrier layer, a hemostatic layer, an antibacterial layer, and an anti-inflammatory layer arranged in sequence, wherein:

[0011] The barrier layer is a polycaprolactone / glacial acetic acid solution, electrospun on one side of the hemostatic layer;

[0012] The hemostatic layer is a gelatin sponge and is located between the barrier layer and the antibacterial layer;

[0013] an antibacterial layer, comprising an antibacterial drug and a first carrier, electrospun on the other side of the hemostatic layer, wherein the first carrier dissolves at a pH greater than 7 and releases the antibacterial drug;

[0014] The anti-inflammatory layer comprises an anti-inflammatory drug and a second carrier, which are electrospun on one side of the antibacterial layer. The second carrier dissolves when the pH value is between 1 and 5 and releases the anti-inflammatory drug.

[0015] According to the above technical solution, preferably, the antibacterial drug is rifampicin, and the first carrier is Eudragit S100.

[0016] According to the above technical solution, preferably, the anti-inflammatory drug is curcumin, and the second carrier is Eudragit E100.

[0017] The present application also discloses a method for preparing a pH-responsive dual-drug-loaded bionic wound dressing, which is used to prepare the above-mentioned pH-responsive dual-drug-loaded bionic wound dressing, comprising the following steps:

[0018] S1. The polycaprolactone is added to glacial acetic acid and mixed thoroughly to form the polycaprolactone / glacial acetic acid solution;

[0019] S2. electrospinning the polycaprolactone / glacial acetic acid solution onto one side of a gelatin sponge to form a barrier layer;

[0020] S3. The Eudragit S100 and rifampicin were added to dimethylformamide and mixed thoroughly to form an S100 / rifampicin solution;

[0021] S4. The S100 / rifampicin solution is electrospun on the other side of the gelatin sponge to form an antibacterial layer;

[0022] S5. The Eudragit E100 and curcumin were added to dimethylformamide and mixed thoroughly to form an E100 / curcumin solution;

[0023] S6. Electrospinning the E100 / curcumin solution onto one side of the antibacterial layer to form an anti-inflammatory layer.

[0024] According to the above technical solution, preferably, in step S1, polycaprolactone is added to glacial acetic acid, and stirred at a constant speed of 500 rpm using a magnetic stirrer at room temperature for 4-8 hours, and after thorough mixing, a polycaprolactone / glacial acetic acid solution with a concentration of 18% is formed.

[0025] According to the above technical solution, preferably, step S2 includes: sucking the polycaprolactone / glacial acetic acid solution into a syringe and installing it on a syringe pump, and controlling the solution flow rate at 80 μL / h; connecting a conductive glass plate and a circuit; adhering a gelatin sponge to the conductive glass plate, and adjusting the distance between the needle of the syringe and the gelatin sponge to 8 mm; turning on the high-voltage power supply and adjusting the voltage to 5.9 kV; and electrospinning on the gelatin sponge for 1 hour to form a barrier layer.

[0026] According to the above technical solution, preferably, step S3 includes: dissolving the Eudragit S100 in dimethylformamide to form a 20% S100 solution; adding rifampicin at a dosage of 3% Eudragit S100 to the S100 solution, stirring at a constant speed of 500 rpm for 2 hours using a magnetic stirrer at room temperature, and forming the S100 / rifampicin solution after thorough mixing.

[0027] According to the above technical solution, preferably, step S5 includes: dissolving the Eudragit E100 in dimethylformamide to form an E100 solution with a concentration of 15%; adding curcumin at a dosage of 0.5% Eudragit E100 to the E100 solution, stirring at a constant speed of 500 rpm using a magnetic stirrer at room temperature for 2 hours, and forming the E100 / curcumin solution after thorough mixing.

[0028] According to the above technical solution, preferably, step S4 or S6 includes: replacing the S100 / rifampicin solution or E100 / curcumin solution in the syringe, and controlling the solution flow rate at 60 μL / h; adjusting the high voltage to 6.2-6.4 kV, and electrospinning on one side of the gelatin sponge or the antibacterial layer for 1 hour to form an antibacterial layer or an anti-inflammatory layer.

[0029] The beneficial effects of the present invention are:

[0030] The present invention prepares a four-layer pH-responsive dual-drug biomimetic wound dressing. Its antibacterial layer and anti-inflammatory layer can release drugs on demand at different pH stages of wound infection, avoiding drug abuse or toxic effects on cells. It can also adapt to different wound thicknesses to achieve higher commercial value.

[0031] In addition, the wound dressing preparation method based on electrospinning technology disclosed in the present invention has simple process steps, high efficiency and low cost, which makes this four-layer pH-responsive dual-drug-loaded bionic wound dressing have extremely high application and promotion value in commercial production and clinical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 It is a schematic diagram of the structural principle of the present invention.

[0033] Figure 2 Figure 3 is the in vitro rifampicin release profile of the biomimetic wound dressing in a medium with a pH value of 4.8.

[0034] Figure 3 Figure 5 is the in vitro rifampicin release profile of the biomimetic wound dressing in a medium with a pH value of 8.

[0035] Figure 4 is the in vitro curcumin release profile of the biomimetic wound dressing in a medium with a pH value of 4.8.

[0036] Figure 5 Figure 5 is the in vitro curcumin release profile of the biomimetic wound dressing in a medium with a pH value of 8.

[0037] Figure 6 The quantitative results of the hemostasis experiment of the pH-responsive dual-drug loaded bionic wound dressing of the present invention are

[0038] Figure 7 It is the quantitative result of the DPPH free radical scavenging experiment of the pH-responsive dual-drug-loaded bionic wound dressing of the present invention.

[0039] Figure 8 The antibacterial properties of Gf-0, Gf-C, Gf-R and Gf-CR against Escherichia coli and Staphylococcus aureus (inhibition zone diameter in mm).

[0040] Figure 9 Figure 3 shows the wound healing status of the full-thickness wound defect model 15 days after treatment with the control group (untreated) and the pH-responsive biomimetic wound dressing.

[0041] Figure 10 It is a schematic diagram of the wound healing rates of the control group and the wound dressing group. DETAILED DESCRIPTION

[0042] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is further described in detail below with reference to the accompanying drawings and the best embodiment. Based on the embodiments of the invention, all other embodiments obtained by those skilled in the art without making any creative work shall fall within the scope of protection of the invention.

[0043] Example 1: As shown in the figure, the present invention comprises a barrier layer, a hemostatic layer, an antibacterial layer, and an anti-inflammatory layer, arranged in sequence. The barrier layer is a polycaprolactone / glacial acetic acid solution electrospun onto one side of the hemostatic layer; the hemostatic layer is a gelatin sponge (its thickness can be adjusted to allow for customized wound dressings of varying thicknesses to accommodate wounds of varying thicknesses) located between the barrier layer and the antibacterial layer. Electrospinning is one of the simplest and most commonly used techniques for creating submicron or nanoscale fiber structures by spraying liquid or molten biopolymers under high pressure. Electrospinning is widely used in wound dressings because it can easily and cost-effectively produce micro- / nanoscale fiber structures that mimic natural ECM structures, and exhibits high porosity, adjustable pore size, a high surface-to-volume ratio, biodegradability, and biocompatibility. The interconnected pores can accommodate drugs, prolonging their release within the human body and ensuring effective therapeutic concentrations. It is an excellent drug carrier and can also effectively absorb wound exudate, thereby promoting wound healing.

[0044] Bionic dressings can better mimic the asymmetric structures and properties of the skin, potentially creating a suitable cellular microenvironment, accelerating the growth of cells involved in skin wound healing, and effectively promoting wound healing. In this case, a polycaprolactone film was prepared using electrospinning technology using a polycaprolactone / glacial acetic acid solution as a barrier layer. This layer is hydrophobic and dense, which helps retain moisture, prevents dehydration and microbial penetration, and provides a physical barrier protection for wound healing, mimicking the skin's epidermis.

[0045] The antibacterial layer of the wound dressing disclosed in the present invention includes an antibacterial drug (rifampicin) and a first carrier (Eudragit S100), which is electrospun on the other side of the hemostatic layer. The first carrier dissolves at a pH greater than 7 and releases the antibacterial drug. The anti-inflammatory layer of the wound dressing disclosed in the present invention includes an anti-inflammatory drug (curcumin) and a second carrier (Eudragit E100), which is electrospun on one side of the antibacterial layer. The second carrier dissolves at a pH between 1 and 5 and releases the anti-inflammatory drug.

[0046] When bacterial infection occurs at a skin wound, the wound's pH changes significantly. Studies have shown that the average pH of healthy skin is typically between 4 and 6, while the pH of a skin wound fluctuates dynamically. When a wound becomes inflamed, the inflamed area has an acidic pH due to increased lactic acid production by anaerobic glycolysis in inflammatory cells. In areas with bacterial infection, the pH rises to between 7.3 and 9.8. Therefore, pH can serve as a natural trigger for topical drug release.

[0047] Polyelectrolyte polymers can impart pH-responsive properties to wound dressings. These polymers contain acidic or basic functional groups on their backbones, capable of releasing or accepting protons depending on the pH of the environment. When the polymer backbone is charged, electrostatic interactions at the molecular level cause molecular chains to rearrange, leading to changes in macroscopic properties such as swelling, solubility, and wettability. The polyelectrolyte polymer acrylic resin (Eudragit) exhibits excellent biocompatibility and film-forming properties, can be used without modification, and exhibits varying pH-sensitive solubility properties, making it widely used in gastrointestinal drug delivery and wound healing. Eudragit S100 (S100) dissolves in media with a pH greater than 7, making it suitable as a carrier for antimicrobial drugs. Eudragit E100 (E100) dissolves in media with a pH between 1 and 5, making it suitable as a carrier for anti-inflammatory drugs. Rifampicin also exhibits excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria. Curcumin is a diketone compound extracted from the rhizomes of plants in the Zingiberaceae and Araceae families. Medical research has shown that curcumin has excellent antioxidant and anti-inflammatory properties, can scavenge reactive oxygen free radicals, and has low toxicity and minimal adverse reactions.

[0048] In summary, during actual use of the pH-responsive dual-drug-loaded bionic wound dressing disclosed in the present invention, when inflammation occurs in the wound, the lactic acid produced by the anaerobic glycolysis of inflammatory cells increases, and the inflamed area has an acidic pH value. Therefore, the E100 in the anti-inflammatory layer can dissolve in an acidic state to release the anti-inflammatory drug curcumin. In the area where bacterial infection occurs, the pH value will rise to between 7.3 and 9.8, and the S100 in the antibacterial layer will dissolve to release the antibacterial drug rifampicin, thereby achieving good on-demand controlled release of drugs to achieve optimal treatment.

[0049] Example 2: This application also discloses a method for preparing a pH-responsive dual-drug-loaded bionic wound dressing, which is used to prepare the above-mentioned pH-responsive dual-drug-loaded bionic wound dressing, comprising the following steps:

[0050] S1. Add polycaprolactone to glacial acetic acid and mix thoroughly to form the polycaprolactone / glacial acetic acid solution. Specifically, in this example, preferably, but not limited to, adding polycaprolactone to glacial acetic acid and stirring at 500 rpm at room temperature for 4-8 hours using a magnetic stirrer to form a polycaprolactone / glacial acetic acid solution with an 18% concentration.

[0051] S2. Electrospin the polycaprolactone / glacial acetic acid solution onto one side of a gelatin sponge to form a barrier layer. Specifically, draw the polycaprolactone / glacial acetic acid solution into a syringe and attach it to a syringe pump, controlling the solution flow rate at 80 μL / h. Connect the conductive glass plate to the circuit. Attach the gelatin sponge to the conductive glass plate, adjusting the distance between the syringe needle and the gelatin sponge to 8 mm. Turn on the high-voltage power supply and adjust the voltage to 5.9 kV. Electrospin the gelatin sponge for 1 hour to form a barrier layer.

[0052] S3. Add the Eudragit S100 and rifampicin to dimethylformamide and mix thoroughly to form an S100 / rifampicin solution. Specifically, in this example, preferably, but not limited to, dissolving Eudragit S100 in dimethylformamide to form a 20% S100 solution; adding rifampicin to the S100 solution at a dosage of 3% Eudragit S100; stirring at 500 rpm for 2 hours at room temperature using a magnetic stirrer to thoroughly mix to form the S100 / rifampicin solution.

[0053] S4. Electrospin the S100 / rifampicin solution onto the other side of the gelatin sponge to form an antibacterial layer. Specifically, replace the S100 / rifampicin solution in the syringe at a flow rate of 60 μL / h. Adjust the high voltage to 6.25 kV and electrospin the solution onto one side of the gelatin sponge for 1 hour to form the antibacterial layer.

[0054] S5. The Eudragit E100 and curcumin are added to dimethylformamide and thoroughly mixed to form an E100 / curcumin solution. Specifically, in this example, preferably but not limited to, Eudragit E100 is dissolved in dimethylformamide to form an E100 solution with a concentration of 15%. Curcumin is added to the E100 solution at a dosage of 0.5% Eudragit E100, and the mixture is stirred at 500 rpm for 2 hours at room temperature using a magnetic stirrer to form the E100 / curcumin solution after thorough mixing.

[0055] S6. Electrospinning the E100 / curcumin solution onto one side of the antibacterial layer to form an anti-inflammatory layer. Specifically, the E100 / curcumin solution was replaced in a syringe at a flow rate of 60 μL / h. The high voltage was adjusted to 6.38 kV, and electrospinning was performed on one side of the antibacterial layer for 1 hour to form the anti-inflammatory layer.

[0056] To achieve pH-responsive drug release, Eudragit S100 and Eudragit E100 were used as drug delivery vehicles for rifampicin and curcumin, respectively. Characterization experiments used an acetate buffer solution with a pH of 4.8 to simulate wound inflammation, and PBS with a pH of 8 to simulate wound bacterial infection. Figure 2-5 The release curves of rifampicin and curcumin from a four-layer pH-responsive biomimetic wound dressing in different release media are depicted. Figure 2 As shown in Figure 2, the release of rifampicin in acetic acid solution was very slow, with only 5.1±1.0% released in 216 h. However, in alkaline PBS, Figure 3 As shown in Figure 2, 97.6±1.2% of rifampicin was released from the wound dressing after 6 hours. Similarly, curcumin also showed rapid release behavior under a specific pH environment. Figure 4 As shown in Figure 2, in acidic medium, curcumin was released rapidly and in large quantities, with 96.4 ± 1.8% of curcumin released after 1 day. However, in alkaline medium, Figure 5 As shown in Figure 3, only 15.0 ± 0.8% of curcumin was released after 9 days. Therefore, this four-layer pH-responsive biomimetic wound dressing can achieve on-demand release of antibacterial and anti-inflammatory drugs.

[0057] like Figure 6 As shown in the characterization experiments, in vitro hemostasis tests were conducted to evaluate the ability of the four-layer pH-responsive biomimetic wound dressing samples to promote blood coagulation after contact with blood, showing the quantitative results of the hemostatic performance of different materials. The wound dressing group had the lowest blood coagulation index, at 62.9±3.6%, and was significantly lower than the traditional gauze and bandage groups. This indicates that the wound dressing has a better hemostatic effect. The good hemostatic performance of the wound dressing is due to the gelatin sponge in its hemostatic layer that promotes platelet aggregation.

[0058] like Figure 7 As shown, the antioxidant activity of the four-layer pH-responsive biomimetic wound dressing was evaluated using a DPPH free radical scavenging assay. The uncurcumin-loaded wound dressing exhibited low antioxidant activity throughout the experiment, reaching 12.0 ± 1.5% after 120 minutes. When the wound dressing was loaded with curcumin, a drug with antioxidant activity, the antioxidant activity increased significantly, and this activity gradually increased over time, indicating that curcumin retained its bioactivity after electrospinning. The wound dressing exhibited the highest antioxidant capacity after 120 minutes, reaching 88.6 ± 2.4%. Therefore, the wound dressing possesses excellent antioxidant activity due to its loaded curcumin, protecting cells from free radical damage.

[0059] It's worth noting that if the body can't effectively eliminate free radicals, it leads to oxidative stress. Oxidative stress and inflammation interact with each other. Reactive oxygen species (ROS) are a primary indicator of oxidative stress. ROS exacerbate inflammation, and inflammation in turn increases ROS production. High levels of ROS can lead to a vicious cycle in wound healing, causing the wound to remain in the inflammatory phase. In summary, antioxidants can have anti-inflammatory effects by reducing inflammation caused by cellular damage caused by free radicals. Therefore, this wound dressing exhibits both excellent antioxidant and anti-inflammatory activities.

[0060] like Figure 8 As shown in the figure, the four-layer pH-responsive biomimetic wound dressings loaded with no drug, curcumin alone, rifampicin alone, and both curcumin and rifampicin were named Gf-0, Gf-C, Gf-R, and Gf-CR, respectively. The antibacterial properties of Gf-0, Gf-C, Gf-R, and Gf-CR were studied by the agar plate disk diffusion method. Figure 8 The results show the antibacterial effects of the four wound dressings against Escherichia coli and Staphylococcus aureus. Gf-0 and Gf-C showed no significant antibacterial activity against these two bacteria. In contrast, Gf-R and Gf-CR, due to their inclusion of rifampicin, exhibited inhibition zones greater than 12 mm in diameter. This indicates that they possess good antibacterial activity against Escherichia coli and Staphylococcus aureus.

[0061] The in vivo wound healing performance of the four-layer pH-responsive biomimetic wound dressing was further evaluated in a full-thickness wound defect model. Figure 9 As shown, the wounds were treated with the control group (untreated) and wound dressings, respectively. As the healing time prolonged, the wound area of ​​the rats in each group continued to shrink. Figure 10 The results showed that from the third day onwards, the wound healing speed of the wound dressing group was significantly faster than that of the control group; on the 15th day, the wound healing rate of the wound dressing group was as high as 93.8±1.9%, which was significantly higher than the wound healing rate of the control group (62.8±8.0%). The wounds of rats treated with wound dressings healed the fastest and had the best healing effect, which may be because the wound dressing contains rifampicin and curcumin. Rifampicin can inhibit the invasion of bacteria into the wound, and curcumin can effectively eliminate excess free radicals in the wound. This protects the proliferation and differentiation of fibroblasts, thereby accelerating the deposition of collagen and the growth of granulation tissue, and promoting wound healing. In addition, the gelatin sponge in the wound dressing has good hemostatic properties, which also accelerates wound healing.

[0062] The present invention prepares a four-layer pH-responsive dual-drug-loaded bionic wound dressing, whose antibacterial layer and anti-inflammatory layer can release drugs on demand at different pH periods of wound infection, avoiding drug abuse or toxic effects on cells, and can match different wound thicknesses to achieve higher commercial value; in addition, the wound dressing preparation method based on electrospinning technology disclosed in the present invention has simple process steps, high efficiency and low cost, which makes this four-layer pH-responsive dual-drug-loaded bionic wound dressing have extremely high application and promotion value in commercial production and clinical applications.

[0063] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A pH-responsive dual-drug loaded bionic wound dressing, characterized in that: It includes a barrier layer, a hemostatic layer, an antibacterial layer and an anti-inflammatory layer arranged in sequence, wherein: The barrier layer is a polycaprolactone / glacial acetic acid solution, electrospun on one side of the hemostatic layer; The hemostatic layer is a gelatin sponge and is located between the barrier layer and the antibacterial layer; an antibacterial layer comprising an antibacterial drug and a first carrier, electrospun on the other side of the hemostatic layer, wherein the first carrier dissolves at a pH greater than 7 and releases the antibacterial drug, wherein the antibacterial drug is rifampicin, and the first carrier is Eudragit S100; The anti-inflammatory layer includes an anti-inflammatory drug and a second carrier, which are electrospun on one side of the antibacterial layer. The second carrier dissolves at a pH of 1-5 and releases the anti-inflammatory drug. The anti-inflammatory drug is curcumin, and the second carrier is Eudragit E100.

2. A method for preparing a pH-responsive dual-drug-loaded bionic wound dressing, for preparing the pH-responsive dual-drug-loaded bionic wound dressing according to claim 1, characterized in that: The steps include: S1. The polycaprolactone is added to glacial acetic acid and mixed thoroughly to form the polycaprolactone / glacial acetic acid solution; S2. electrospinning the polycaprolactone / glacial acetic acid solution onto one side of a gelatin sponge to form a barrier layer; S3. The Eudragit S100 and rifampicin were added to dimethylformamide and mixed thoroughly to form an S100 / rifampicin solution; S4. The S100 / rifampicin solution is electrospun on the other side of the gelatin sponge to form an antibacterial layer; S5. The Eudragit E100 and curcumin were added to dimethylformamide and mixed thoroughly to form an E100 / curcumin solution; S6. Electrospinning the E100 / curcumin solution onto one side of the antibacterial layer to form an anti-inflammatory layer.

3. The method for preparing a pH-responsive dual-drug-loaded bionic wound dressing according to claim 2, characterized in that: In step S1, polycaprolactone is added to glacial acetic acid, and stirred at a constant speed of 500 rpm using a magnetic stirrer at room temperature for 4-8 hours, and after thorough mixing, a polycaprolactone / glacial acetic acid solution with a concentration of 18% is formed.

4. The method for preparing a pH-responsive dual-drug-loaded bionic wound dressing according to claim 3, characterized in that: Step S2 includes: sucking the polycaprolactone / glacial acetic acid solution into a syringe and installing it on a syringe pump, with the solution flow rate controlled at 80 μL / h; connecting a conductive glass plate and a circuit; adhering a gelatin sponge to the conductive glass plate, and adjusting the distance between the syringe needle and the gelatin sponge to 8 mm; turning on a high-voltage power supply and adjusting the voltage to 5.9 kV; and electrospinning the gelatin sponge for 1 hour to form a barrier layer.

5. The method for preparing a pH-responsive dual-drug-loaded bionic wound dressing according to claim 2, characterized in that: Step S3 comprises: dissolving the Eudragit S100 in dimethylformamide to form a 20% S100 solution; adding rifampicin at a dosage of 3% Eudragit S100 to the S100 solution, stirring at a constant speed of 500 rpm using a magnetic stirrer at room temperature for 2 hours, and thoroughly mixing to form the S100 / rifampicin solution.

6. The method for preparing a pH-responsive dual-drug-loaded bionic wound dressing according to claim 5, characterized in that: Step S5 comprises: dissolving the Eudragit E100 in dimethylformamide to form an E100 solution with a concentration of 15%; adding curcumin at a dosage of 0.5% Eudragit E100 to the E100 solution, stirring at a constant speed of 500 rpm using a magnetic stirrer at room temperature for 2 hours, and fully mixing to form the E100 / curcumin solution.

7. The method for preparing a pH-responsive dual-drug-loaded bionic wound dressing according to claim 6, characterized in that: Step S4 or S6 includes: replacing the S100 / rifampicin solution or E100 / curcumin solution in the syringe, and controlling the solution flow rate at 60 μL / h; adjusting the high voltage to 6.2-6.4 kV, and electrospinning on one side of the gelatin sponge or antibacterial layer for 1 hour to form an antibacterial layer or anti-inflammatory layer.

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