Preparation method of hydrogel microneedle dressing and application of hydrogel microneedle dressing in preparation of wound management dressing

Abstract

The invention provides a preparation method of a hydrogel microneedle dressing, which comprises the following steps: fully dissolving chitosan in a glacial acetic acid aqueous solution to obtain a chitosan solution; the preparation method comprises the following steps: respectively dissolving polyvinyl alcohol and polyvinylpyrrolidone in water to obtain a polyvinyl alcohol solution and a polyvinylpyrrolidone solution; mixing the obtained solutions to obtain a hydrogel prepolymerization solution; and injecting the hydrogel pre-polymerized liquid into a hole of a microneedle mold by repeatedly vacuumizing, standing to form gel, drying and demolding to obtain the hydrogel microneedle dressing. The hydrogel microneedle dressing prepared in the invention has the advantages of excellent mechanical properties, good hemostatic performance, bacteriostasis, anti-inflammation and liquid absorption capability; when in use, the hemostatic gel can rapidly swell after penetrating through the cuticle, absorb tissue exudate and rapidly form a blood coagulation barrier, the hemostatic efficiency is enhanced through dual mechanisms of positive charge adsorption and blood coagulation factor activation, inflammatory factors are continuously inhibited, and rapid hemostasis, antibiosis and anti-inflammation are realized.

Description

Technical Field

[0001] The present invention relates to the technical field of medical dressings, and in particular to a method for preparing a hydrogel microneedle dressing and application of the hydrogel microneedle dressing in preparing a wound management dressing. Background Art

[0002] With the rapid development of trauma medicine, chronic wound management and cosmetic surgery, wound care technology is undergoing a transformation from traditional passive protection to active intervention treatment. Although traditional dressings (such as gauze and cotton pads) can temporarily cover the wound, they have defects such as easy adhesion to the wound, limited absorption capacity and insufficient antibacterial properties, which lead to prolonged healing period and increased risk of scar hyperplasia in patients. As a new generation of medical materials, hydrogel dressings achieve high water content (>90%) and intelligent osmotic regulation capabilities by constructing a three-dimensional network structure, showing significant advantages in maintaining a moist healing environment, reducing inflammatory responses and promoting tissue regeneration.

[0003] In the field of medical emergency and surgical operations, rapid, effective and safe hemostasis is a key step in saving patients' lives and reducing complications, especially for incision-type wounds. Due to the large wound surface, rapid and effective hemostasis is required while also having anti-inflammatory and antibacterial properties. Traditional hemostatic materials such as gauze and sponges, although they can absorb blood and form a physical barrier, have a slow hemostasis speed and lack the antibacterial and wound healing functions. Hemostatic dressings are now commonly used in medical treatment, but existing hemostatic dressings still have shortcomings in hemostasis speed, antibacterial effect and biocompatibility.

[0004] In recent years, microneedle technology has gradually been used in the fields of drug delivery and wound care because of its ability to penetrate the skin's stratum corneum and directly act on the dermis. However, the existing microneedle dressings still need to be improved in terms of mechanical properties, hemostatic efficiency and biocompatibility. Summary of the Invention

[0005] The purpose of the present invention is to provide a hydrogel microneedle dressing for postoperative wound management, which is suitable for incision-type wounds. It uses microneedle technology to achieve rapid hemostasis, exudate absorption, antibacterial and anti-inflammatory effects and promote healing of wounds. It has excellent mechanical properties and good biocompatibility.

[0006] A hydrogel microneedle dressing is used in preparing a hydrogel microneedle dressing for wound management.

[0007] Furthermore, the raw materials for preparing the hydrogel microneedle dressing include chitosan, polyvinyl alcohol, and polyvinyl pyrrolidone in a weight ratio of (1-8): (1-8): (1-10).

[0008] Furthermore, the diameter of the bottom surface of the microneedles of the hydrogel microneedle dressing is 100-1000 μm; the spacing between the microneedles is 500-1500 μm; and the height of the microneedles is 200-1500 μm.

[0009] Furthermore, the bottom diameter of the microneedle is 710-730 μm; the spacing between the microneedles is 1140-1160 μm; and the height of the microneedle is 990-1010 μm.

[0010] A method for preparing a hydrogel microneedle dressing comprises the following steps:

[0011] Step (1): fully dissolving chitosan in a glacial acetic acid aqueous solution to obtain a chitosan solution;

[0012] Step (2): dissolving polyvinyl alcohol and polyvinyl pyrrolidone in water respectively to obtain a polyvinyl alcohol solution and a polyvinyl pyrrolidone solution, and mixing them to form a mixed solution;

[0013] Step (3): mixing the solutions obtained in step (1) and step (2) to obtain a hydrogel prepolymer solution;

[0014] Step (4): The hydrogel prepolymer obtained in step (3) is injected into the microneedle mold by repeated vacuuming, allowed to stand to form a gel, and then dried and demoulded to obtain a hydrogel microneedle dressing.

[0015] Furthermore, the volume ratio of glacial acetic acid to water in the glacial acetic acid aqueous solution is (1-5):100; and the amount ratio of chitosan to glacial acetic acid aqueous solution in the chitosan solution is 1-10 g / 100 mL.

[0016] Furthermore, the ratio of polyvinyl alcohol to water in the polyvinyl alcohol solution is 1-10 g / 100 mL.

[0017] Furthermore, the dosage ratio of polyvinyl pyrrolidone to water in the polyvinyl pyrrolidone solution is 5-50 g / 100 mL.

[0018] Furthermore, the volume ratio of the polyvinyl alcohol solution to the polyvinyl pyrrolidone solution in the mixed solution is 1-10:1-10.

[0019] Furthermore, the volume ratio of the chitosan solution to the mixed solution is 1-10:1-10.

[0020] This hydrogel microneedle dressing has a puncture force greater than 0.098N / needle, an inhibition zone diameter ≥8mm, and a cell survival rate >90%. Furthermore, the hydrogel microneedle dressing combines portability (patch form) with biosafety (degradable material, with a degradation rate of >80% within 28 days).

[0021] Beneficial effects of the present invention:

[0022] The hydrogel microneedle dressing patch of the present invention is suitable for post-surgical wound management, chronic wound care (such as diabetic foot and bedsores), minimally invasive surgical hemostasis, and battlefield first aid. After puncturing the skin, the microneedles quickly form a coagulation barrier and enhance hemostasis efficiency through a dual mechanism of positive charge adsorption and coagulation factor activation. Simultaneously, after penetrating the stratum corneum, the microneedles rapidly adsorb and swell, continuously inhibiting inflammatory factors and promoting fibroblast migration. It has significant antibacterial effects, is non-cytotoxic, and has good biocompatibility.

[0023] The present invention is based on chitosan polymer, which is mixed with polyvinyl alcohol and polyvinyl pyrrolidone in proportion and then injected into the microneedle mold. Chitosan has biocompatibility, low immunogenicity and hemostatic and antibacterial properties, polyvinyl alcohol enhances mechanical strength, and polyvinyl pyrrolidone regulates swelling and exudate adsorption. Under the synergistic cross-linking effect of the three, the obtained hydrogel microneedle dressing has good transdermal and swelling effects. When the microneedles of the hydrogel microneedle dressing penetrate the subcutaneous tissue or absorb chronic wound exudate, on the one hand, the hydrogel microneedles puncture the skin, activate coagulation factors, promote platelet activation, enhance platelet aggregation and contraction, thereby quickly forming a coagulation barrier, and on the other hand, the hydrogel microneedles swell rapidly, exerting cationic properties, and combining with the negatively charged red blood cell membrane surface through positive charge to promote red blood cell aggregation, thereby forming blood clots. Under the dual mechanism, the hemostatic effect is greatly improved, which is suitable for postoperative wound management and hemostasis of incision-type wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 :Characterization of the morphology of hydrogel microneedle dressing; (A) micrograph; (B) SEM image;

[0025] Figure 2 : Characterization of swelling properties of hydrogel microneedle dressing;

[0026] Figure 3 :Characterization of mechanical properties of hydrogel microneedle dressing;

[0027] Figure 4 :OCT transdermal performance characterization of hydrogel microneedle dressing; (A) cross section; (B) longitudinal section;

[0028] Figure 5 : Characterization of the transdermal performance of hydrogel microneedle dressing; (A) real-life image; (B) fluorescence image; (C) white light image;

[0029] Figure 6 : Characterization of the hemostatic performance of hydrogel microneedle dressing; (A) Actual photos; (B) Hemostatic time statistics; (C) Hemostatic time bar graph;

[0030] Figure 7 : Hemostatic performance of hydrogel microneedle dressing; (A) hemostatic time; (B) coagulation index;

[0031] Figure 8 :Safety performance characterization of hydrogel microneedle dressing; (A) Different CCK-8 groups; (B) Different CCK-8 concentrations; (C) Hemolysis;

[0032] Figure 9 :Characterization of antibacterial properties of hydrogel microneedle dressing; (A) inhibition zone; (B) inhibition rate; (C) bacterial activity;

[0033] Figure 10 :Characterization of anti-inflammatory properties of hydrogel microneedle dressing; (A) IL-6; (B) TNF-α;

[0034] Figure 11 :A clinical trial case of hydrogel microneedle dressing;

[0035] Figure 12 :A case study of a clinical trial of hydrogel microneedle dressing. DETAILED DESCRIPTION

[0036] In order to make the technical means, creative features, objectives and effects achieved by the present invention easier to understand, the present invention is further described below in conjunction with specific implementation methods.

[0037] Example 1

[0038] Preparation of hydrogel microneedles:

[0039] (1) Chitosan was fully dissolved in water containing 2 v / v% glacial acetic acid, i.e., the volume ratio of glacial acetic acid to water was 2:98, to obtain a 5 g / 100 mL chitosan solution;

[0040] (2) dissolving polyvinyl alcohol and polyvinyl pyrrolidone in water to obtain a 5 g / 100 mL polyvinyl alcohol aqueous solution and a 40 g / 100 mL polyvinyl pyrrolidone aqueous solution, respectively; then mixing the polyvinyl alcohol aqueous solution and the polyvinyl pyrrolidone aqueous solution in a volume ratio of 1:1 to form a mixed solution;

[0041] (3) mixing the solutions in step (1) and step (2) in a certain volume ratio of 1:1 to obtain a hydrogel prepolymer solution;

[0042] (4) At room temperature, the solution (3) was poured into the PDMS mold, and degassed in a vacuum drying oven with a vacuum degree of -0.1 MPa for 3 minutes. The hydrogel prepolymer was pressed into the microneedle mold by repeated vacuuming 3 times. After standing at room temperature for 8 hours to form a gel, the hydrogel microneedle was dried and demolded.

[0043] Example 2

[0044] Preparation of chitosan microneedles:

[0045] (1) Chitosan was fully dissolved in water containing 2 v / v% glacial acetic acid, i.e., the volume ratio of glacial acetic acid to water was 2:100, to obtain a 5 g / 100 mL chitosan solution;

[0046] (2) At room temperature, the solution (1) was poured into the PDMS mold, and degassed in a vacuum drying oven with a vacuum degree of -0.1 MPa for 3 minutes. The hydrogel prepolymer was repeatedly vacuumed three times to press into the microneedle mold. After standing at room temperature for 8 hours to form a gel, the mold was dried and demolded to obtain chitosan microneedles.

[0047] Example 3

[0048] Preparation of PVP+PVA microneedles:

[0049] (1) dissolving polyvinyl alcohol and polyvinyl pyrrolidone in water to obtain a 5 g / 100 mL polyvinyl alcohol aqueous solution and a 40 g / 100 mL polyvinyl pyrrolidone aqueous solution, respectively; then mixing the polyvinyl alcohol aqueous solution and the polyvinyl pyrrolidone aqueous solution in a volume ratio of 1:1 to form a mixed solution;

[0050] (2) At room temperature, the solution (1) was poured into the PDMS mold, and degassed in a vacuum drying oven with a vacuum degree of -0.1 MPa for 3 minutes. The hydrogel prepolymer was repeatedly vacuumed three times to press into the microneedle mold. After standing at room temperature for 8 hours to form a gel, it was dried and demolded to obtain PVP+PVA microneedles.

[0051] Actual photos, microscopic and SEM images of hydrogel microneedles Figure 1 As shown, the microneedles exhibit a regular conical arrangement of tips, with intact needle structures and smooth surfaces. Stereoscopic microscopy and SEM evaluation confirmed the microneedle geometry to be a three-dimensional conical shape, with a vertical and horizontal spacing of approximately 1150μm between the needle centers and a base diameter of 720μm, meeting design requirements. The uniform size and angle of the tips facilitated penetration of the stratum corneum.

[0052] Water absorption and swelling process of hydrogel microneedles: record the water absorption and swelling of hydrogel microneedles at different time points, weigh the freeze-dried hydrogel, the original mass is W0, then put the hydrogel into PBS solution (0.01M, pH7.4), once the preset time interval is reached, remove the hydrogel from the PBS solution and use filter paper to remove excess water. Record the weight of the hydrogel at different times as W t , until the hydrogel reaches swelling equilibrium, and the swelling rate is obtained;

[0053] Swelling rate calculation formula: Swelling rate (%) = (W t -W0) / W0×100%;

[0054] The results are as follows Figure 2As shown, the swelling behavior of the microneedles at different time points was recorded, and the swelling properties of the gel were further tested using the bag method. The test results are shown in Figure 2 As shown in B, the gel gradually absorbs water and swells in the PBS solution. After about 60 seconds, the swelling equilibrium is gradually reached. At the final swelling equilibrium, the swelling rate of the gel is about 280%.

[0055] Mechanical property test of hydrogel microneedles: The penetration force and mechanical strength of hydrogel microneedles were tested. The microneedles were vertically compressed using a constant compression rate mode at a compression rate of 8 μm / s. The maximum compression displacement of the sample was 400 μm. Three microneedles were randomly selected from samples 1, 2, and 3, and compression tests were performed using a high-precision single-needle microneedle strength tester. The results are shown in Figure 2. Figure 3 As shown, the axial force test verified that the microneedle can effectively penetrate the human stratum corneum under a force of 0.098N.

[0056] Hydrogel microneedle skin test:

[0057] OCT transdermal experiment operation: Place the glass slide with the pig skin sample fixed on the sample stage of the instrument, adjust the position so that the scanning probe is aimed at the center of the skin sample, and obtain the skin OCT image; the results are as follows Figure 4 As shown, optical coherence tomography (OCT) is a non-invasive imaging technology based on the principle of low-coherence interference. Its core advantages lie in high resolution (axial resolution 1-15μm, lateral resolution 3-20μm) and deep penetration (up to 2mm). It can capture the dynamic changes of the microneedle transdermal process in real time. In the study of hydrogel microneedle transdermal penetration, OCT achieves precise analysis through the following mechanisms: Quantification of microneedle penetration depth: The actual penetration depth of the microneedle after insertion into the skin is measured through B-scan images (cross-section) (such as stratum corneum penetration rate >95%, dermis penetration rate 80%).

[0058] Pathological transdermal test:

[0059] 1. Source:

[0060] The microneedle patch was inserted into the back of the hairless mouse for 2 hours, and then the mouse was killed. The skin tissue of the mouse at the patch was taken and 4w / v% The tissue was fixed with paraformaldehyde solution (4 g PFA dissolved in 100 mL PBS solution with pH = 7.4);

[0061] 2. Quick freezing:

[0062] After sampling, the tissue block should be quickly frozen immediately. Place the tissue block flat in a soft plastic bottle cap or a special small box (about 2 cm in diameter). If the tissue block is small, add an appropriate amount of OCT embedding medium to immerse the tissue. Then, slowly place the special small box flat in a small cup filled with liquid nitrogen. When the bottom of the box contacts the liquid nitrogen, it will begin to vaporize and boil. At this time, the small box should remain in place and not be immersed in liquid nitrogen. After the frozen block is made, place it in a constant temperature box microtome for frozen sectioning;

[0063] 3. Fixation:

[0064] Apply a layer of OCT embedding gel on the sample holder, place the quick-frozen tissue on it, pre-cool in a 4°C refrigerator for 10 minutes to allow the OCT gel to penetrate the tissue, remove the tissue and place it on tin foil or a glass slide, quick-freeze the sample holder, place the tissue on the sample holder, and add another layer of OCT gel to completely cover it. Place it on a quick-freeze rack (PE) for 30 minutes;

[0065] 4. Slicing:

[0066] Use a constant temperature freezing microtome at -15°C when slicing. Attach the tissue sections to the slides and do not move them up and down. After cutting, place them at room temperature for 30 minutes, then place them in 4°C acetone solution for 10 minutes, oven-dry for 20 minutes, and wash them with PBS solution for 5 minutes. Repeat this three times. Perform antigen heat repair. Microwave heat repair is also acceptable. Cool naturally at room temperature and incubate them in 3% hydrogen peroxide solution for 10 minutes to eliminate endogenous peroxidase activity.

[0067] 5. Immunofluorescence staining:

[0068] The frozen sections were dried at room temperature for 15 minutes, and then blocked with PBS solution containing 10% normal goat serum for 1 hour at room temperature (no need to wash at this step), and then covered with a clean cover glass. The sections were observed and photographed using a film scanner. The cross-section and longitudinal section results were as follows: Figure 5 As shown: After the hydrogel microneedles penetrated the pig skin, a clear microneedle array was left. After the microneedles penetrated, the depression caused by the microneedles was clearly visible. The depth was greater than 400μm, indicating that the microneedles had good skin penetration results.

[0069] Hydrogel microneedle hemostasis test:

[0070] Experiment 1: Hemostasis time

[0071] Take 250 μL of citrated whole blood and 25 μL of 0.1 mol / L CaCl2 solution, preheat at 37°C for 30 min, and gently mix. The calcified blood was added dropwise to 1.5 mL centrifuge tubes containing 50 mg of gauze, 50 mg of dry PVP+PVA microneedles, and 50 mg of dry hydrogel microneedles, respectively. These tubes were used as the control group, PVP+PVA experimental group, and hydrogel microneedle experimental group, respectively. The centrifuge tubes were inverted every 3 seconds to observe whether clots were formed. The hemostasis time was recorded immediately after clot formation.

[0072] Experiment 2: Coagulation Index Test

[0073] Gauze, 50 mg hydrogel xerogel and 50 mg hydrogel microneedle samples were preheated in 37 ° C deionized water in advance and placed in a centrifuge tube as blank control, hydrogel and hydrogel microneedle experimental groups, respectively. The blank control was also a negative control. A mixture of 0.4 mL of mouse whole blood and 0.04 mL of sodium citrate solution (concentration of 38 mg / mL) was slowly added to each experimental group, and 30 μL of calcium chloride solution (concentration of 0.2 mol / L) was added to start coagulation. The temperature of the process was maintained at 37 ° C. After 10 minutes, 10 mL of deionized water was slowly added, and 10 mL of liquid was collected and centrifuged. The supernatant was taken, 20 mL of deionized water was added, and it was transferred to a new centrifuge tube and kept in a 37 ° C water bath for 1 hour. The absorbance of each experimental group at 540 nm was measured using a microplate reader (recorded as a), and the absorbance of 0.4 mL of citric acid whole blood mixed with 30 mL of deionized water was measured (recorded as b);

[0074] The blood coagulation index (BCI) was calculated as follows: BCI (%) = (a / b) × 100%;

[0075] The results are as follows Figure 6-7 As shown in the results, the hydrogel microneedles showed excellent hemostatic effect in the in vitro whole blood model, with an average hemostasis time of 93±5 seconds. The mechanism may be that the hydrogel absorbs blood moisture and promotes platelet aggregation. It is mentioned that hemostatic performance needs to be evaluated in combination with mechanical strength and biocompatibility. In this experiment, the rapid hemostasis advantage of the hydrogel microneedles was verified by gauze and PVP+PVA controls. At the same time, the trend of the coagulation index change also shows that with the passage of time, the coagulation index of the hydrogel group and the hydrogel microneedle group has steadily decreased, further reflecting the high efficiency and stability of the coagulation process.

[0076] Hydrogel microneedle material safety testing (CCK-8 and hemolysis):

[0077] Experiment 1: CCK-8

[0078] Fibroblasts were grown in a culture medium containing 10% FBS for modeling. The growth conditions were 5% CO2 and a 37°C incubator. Cells in the logarithmic phase were treated with trypsin to obtain a cell suspension. 1×104 cells were seeded in each well of a 96-well plate. The 96-well plate was placed in an incubator and incubated. After 24 hours, the culture medium was discarded and replaced with gel extracts of different groups and concentrations. A blank group was set up with 3 parallel samples in each group. The cells were placed in an incubator and incubated for 24 hours. The liquid was discarded after 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours, and 100 μL of culture medium (containing 10 μL CCK-8) was replaced in each well. The cells were continued to be incubated in a cell culture incubator at 37°C and 5% CO2 for 2 hours. The absorbance (OD) value of each solution at 450 nm was measured with a microplate reader to obtain the cell survival rate.

[0079] The calculation formula of cell survival rate is: cell survival rate = (absorbance value of experimental group / absorbance value of blank group) × 100%;

[0080] Experiment 2: Hemolysis experiment

[0081] Rat whole blood was mixed with 109 mmol / L sodium citrate in a 9:1 ratio and centrifuged at 3000 rpm for 5 min to obtain red blood cells. The red blood cells were washed with PBS solution and diluted to a 5% v / v suspension concentration. 50 mg of materials from different groups were weighed, and then 0.5 mL of red blood cells were added to a 1.5 mL tube and mixed thoroughly. All tubes were incubated at 37°C for 1 h and centrifuged at 10000 rpm for 10 min. 200 μL of supernatant was carefully transferred to a 96-well plate and the absorbance (Am) of the supernatant at 562 nm was read using a microplate reader (S / N 3052431277, Molecular Devices). Samples treated with deionized water and PBS solution were used as positive controls (Ah) and negative controls (Ap), respectively. Samples treated with chitosan, PVA+PVP, and hydrogel microneedles were designated as the chitosan group, PVA+PVP group, and hydrogel microneedle group, respectively, to obtain the hemolysis rate.

[0082] The hemolysis rate of the gel was calculated using the following formula: hemolysis rate (%) = (Am-Ap) / (Ah-Ap) × 100%;

[0083] The results are as follows Figure 8 As shown, the experiment showed that the cell survival rate of microneedle dissolving solution at different concentrations was >90%, and the hemolysis rate was <5%, which met the biosafety standards and showed that the hydrogel microneedle dressing material had no significant cytotoxicity.

[0084] Antibacterial test of hydrogel microneedle dressing (inhibition zone, inhibition rate and bacterial activity):

[0085] To test the antibacterial effect of hydrogel microneedle dressing on Staphylococcus aureus, an appropriate amount of Staphylococcus aureus liquid (109 CFUs / ml) was added to a solid culture medium of Staphylococcus aureus that had been cooled to about 50°C, mixed evenly, poured into a plate, and allowed to stand horizontally for solidification. The group that did not receive any subsequent treatment was the blank control group, while the group that subsequently received PVA+PVP microneedles and hydrogel microneedles on the solidified plate was the PVA+PVP microneedle group and the hydrogel microneedle group, respectively. Each group was repeated three times and cultured for 24 hours. The size of the inhibition zone was measured, and the concentration of the bacterial solution was measured by a spectrophotometer to calculate the inhibition rate and bacterial viability.

[0086] The inhibition rate and survival rate were calculated according to the formula:

[0087] Inhibition rate (%) = (OD value of blank group - OD value of experimental group) / OD value of blank group × 100%;

[0088] Survival rate % = (CFU of test group / CFU of control group) × 100%;

[0089] The results are as follows Figure 9 As shown, the diameter of the inhibition zone of the hydrogel microneedle dressing against Staphylococcus aureus reached 8±1mm, the inhibition rate was >85%, and the bacterial activity was reduced to 15% of that of the control group.

[0090] Hydrogel microneedle anti-inflammatory test (IL-6 and TNF-α):

[0091] To test the inhibitory effect of hydrogel microneedles on inflammatory factors, RAW264.7 cells were cultured in DMEM + 10% FBS medium at 37°C and 5% CO2 until they reached 80% confluence and seeded in 6-well plates (2×10 5 cells / well) and adhered for 24 h. The cells were treated according to the following components: the control group used healthy tissue without inflammation induction or any intervention; the model group used inflammation induction (such as LPS stimulation or skin injury model) without dressing intervention; the PVP+PVA group used inflammation induction and then applied a blank dressing containing 15% PVP (polyvinyl pyrrolidone) and 10% PVA (polyvinyl alcohol); the hydrogel microneedle group used inflammation induction and then applied a hydrogel microneedle dressing (microneedle length 300 μm, drug loading 0.5 mg / cm 2 ), with at least 6 biological replicates per group, the dressing was applied for 24 hours, and the cells were cultured at 37°C and 5% CO2. The IL-6 and TNF-α levels in the cells of each experimental group were detected using Elisa kits. The capture antibody was fixed in a 96-well microtiter plate. After incubation, biotinylated detection antibody (unit: Abcam), enzyme marker (such as HRP) and substrate were added in sequence. The absorbance was measured at 450 nm using a spectrophotometer, and the concentration was calculated according to the standard curve. The results are shown in Figure 2. Figure 10As shown, the concentrations of inflammatory factors IL-6 and TNF-α in the hydrogel microneedle-treated group decreased by 60% and 55%, respectively, indicating that the hydrogel microneedle has significant anti-inflammatory properties.

[0092] like Figure 11 and Figure 12 Shown is a case study of a clinical trial of hydrogel microneedle dressing.

[0093] Case 1: A 66-year-old female patient was admitted to the hospital for coronary artery disease and angina pectoris and underwent coronary angiography. She received 2000 units of heparin during the procedure, but no interventional therapy was performed. The compression hemostatic device was removed three hours after the procedure, with no bleeding or hematoma. This was five hours earlier than in patients who did not receive the microneedle dressing.

[0094] Figure 11 Figure A shows the radial artery sheath retained after angiography; Figure B shows the application of a compression device after the microneedle dressing is applied; Figure C shows the removal of the compression device 3 hours later, with the dressing retained on the wound to exert its anti-inflammatory and antibacterial effects; Figures D and E show the postoperative wound and the appearance of the microneedle dressing after use, which are almost completely healed.

[0095] Case 2: A 72-year-old male patient was admitted to the hospital for coronary artery disease and angina pectoris and underwent coronary angiography. He received 2000 units of heparin during the procedure, but no interventional therapy was performed. The compression hemostatic device was removed three hours after the procedure, with no bleeding or hematoma. This was five hours earlier than in patients who did not receive the microneedle dressing.

[0096] Figure 11 Figure A shows the radial artery sheath retained after angiography; Figure B shows the application of a compression device after the microneedle dressing is applied; Figure C shows the removal of the compression device 3 hours later, with the dressing retained on the wound to exert its anti-inflammatory and antibacterial effects; Figures D and E show the postoperative wound and the appearance of the microneedle dressing after use, which are almost completely healed.

[0097] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It is obvious to those skilled in the art that the present invention is not limited to the details of the above exemplary embodiments, and that the present invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention. Therefore, from all points of view, the embodiments should be regarded as illustrative and non-restrictive. The scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes that fall within the meaning and range of equivalents of the claims are included in the present invention. Any reference signs in the claims should not be construed as limiting the claim to which they relate.

[0098] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. Application of a hydrogel microneedle dressing in the preparation of a hydrogel microneedle dressing for wound management.

2. The use according to claim 1, characterized in that The raw materials for preparing the hydrogel microneedle dressing include chitosan, polyvinyl alcohol and polyvinyl pyrrolidone in a weight ratio of (1-8): (1-8): (1-10).

3. The use according to claim 1, characterized in that The diameter of the bottom surface of the microneedles of the hydrogel microneedle dressing is 100-1000 μm; the spacing between the microneedles is 500-1500 μm; and the height of the microneedles is 200-1500 μm.

4. A method for preparing a hydrogel microneedle dressing, which is used in preparing a hydrogel microneedle dressing for wound management, characterized in that: The following steps are involved: Step (1): fully dissolving chitosan in a glacial acetic acid aqueous solution to obtain a chitosan solution; Step (2): dissolving polyvinyl alcohol and polyvinyl pyrrolidone in water respectively to obtain a polyvinyl alcohol solution and a polyvinyl pyrrolidone solution, and mixing them to form a mixed solution; Step (3): mixing the solutions obtained in step (1) and step (2) to obtain a hydrogel prepolymer solution; Step (4): The hydrogel prepolymer obtained in step (3) is injected into the microneedle mold by repeated vacuuming, allowed to stand to form a gel, and then dried and demoulded to obtain a hydrogel microneedle dressing.

5. The method for preparing the hydrogel microneedle dressing according to claim 4, characterized in that: The volume ratio of glacial acetic acid to water in the glacial acetic acid aqueous solution is (1-5):

100.

6. The method for preparing the hydrogel microneedle dressing according to claim 4, characterized in that: The amount ratio of chitosan to glacial acetic acid aqueous solution in the chitosan solution is 1-10 g / 100 mL.

7. The preparation method according to claim 4, characterized in that The dosage ratio of polyvinyl alcohol to water in the polyvinyl alcohol solution is 1-10 g / 100 mL.

8. The method for preparing the hydrogel microneedle dressing according to claim 4, characterized in that: The dosage ratio of polyvinyl pyrrolidone to water in the polyvinyl pyrrolidone solution is 5-50 g / 100 mL.

9. The method for preparing the hydrogel microneedle dressing according to claim 4, characterized in that: The volume ratio of the polyvinyl alcohol solution to the polyvinyl pyrrolidone solution in the mixed solution is 1-10:1-10.

10. The method for preparing the hydrogel microneedle dressing according to claim 4, characterized in that: The volume ratio of the chitosan solution to the mixed solution is 1-10:1-10.

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