Gel dressing for skin wound repair and preparation method thereof

Abstract

The invention belongs to the technical field of bioengineering medicines, and particularly relates to a gel dressing for repairing skin wounds and a preparation method of the gel dressing. The anti-fouling coating is prepared from the following raw materials in parts by weight: 65 to 75 parts of polyvinyl alcohol, 14 to 20 parts of sodium alginate, 4 to 8 parts of sodium carboxymethyl cellulose, 1 to 3 parts of sodium hyaluronate, 12 to 22 parts of glycerol, 1 to 3 parts of surface anti-fouling additive, 6 to 10 parts of antibacterial microcapsule and 2 to 2.8 parts of compound ion. According to the invention, a PVA freeze-thaw physical network and an alginic acid Ca / Zn composite ion network cooperate to limit a pore channel, so that stable forming is realized; a chitosan / sodium tripolyphosphate microcapsule is prepared from polyhexamethylene biguanide hydrochloride and covered with sodium alginate, release sensitive to pH / ionic strength, acceleration in an inflammation stage and self-limiting in a later stage are constructed, and long-acting bacteriostasis is formed by SA-Zn site slow release; the stability and staged adaptation are highlighted through processes such as encapsulation, low-shear doping and the like and raw material synergy.

Description

Technical Field

[0001] The invention belongs to the technical field of bioengineering medicine, and particularly relates to a gel dressing for repairing skin wounds and a preparation method thereof. Background Art

[0002] Skin wound healing is a multifactorial process involving four consecutive stages: hemostasis, inflammation, proliferation, and remodeling. Its microenvironment changes dynamically over time: exudate and protein load are higher in the early stages, the pH is often alkaline and prone to the growth of bacteria and biofilms, and then gradually shifts to the needs of cell migration, collagen deposition, and epithelial closure. Modern moist healing theory has been widely accepted. Compared with traditional dry dressings such as cotton yarn and gauze, moist dressings can accelerate keratinocyte crawling, promote granulation tissue formation, and reduce secondary damage during dressing changes by maintaining moderate moisture and gas exchange. In this system, gel dressings are regarded as an important material platform for covering various superficial wounds and chronic, difficult-to-heal wounds due to their high water content, soft fit, good biocompatibility, and drug loading.

[0003] The base materials of common gel dressings include two major categories: natural and synthetic. Natural polysaccharides such as alginate, hyaluronic acid, chitosan, carboxymethyl cellulose, etc. have good hydrophilicity and cell compatibility, and can quickly form gels through ionic or hydrogen bond networks; synthetic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, polyurethane, etc. have controllable structures and properties and mature preparation processes. The network formation method usually adopts physical crystallization (such as polyvinyl alcohol freeze-thaw), ionic crosslinking (such as alginate-calcium coordination), or photo / chemical crosslinking to obtain the required mechanics and homeostasis. With the increase in clinical needs, antibacterial factors (silver, iodine, etc.), exudation management components, extracellular matrix simulation molecules and repair-promoting active substances have been gradually introduced, making gel dressings evolve from simple barrier materials to multifunctional microenvironment regulation carriers. Despite this, the existing technology still faces several common problems. The "moist but not too wet" window is difficult to maintain continuously. In scenarios with abundant exudate or frequent site activity, the single ion network is prone to swelling, softening, or even structural collapse. Conversely, during the exudate reduction stage, the dressing may dry out and adhere, increasing pain during dressing changes and secondary damage. In addition, directly incorporating silver, antibiotics, or cationic bactericides into the matrix often results in a contradiction between early burst release and later weakness. There are also disputes over discoloration, protein binding inactivation, or compatibility between silver and some small molecules. Therefore, based on the above-mentioned defects, it is extremely necessary to develop a gel dressing with high stability, long-lasting antibacterial properties, and phased adaptability. Summary of the Invention

[0004] In view of the defects of the prior art, the purpose of the present invention is to provide a gel dressing for skin wound repair and its preparation method. In order to solve the problems of easy collapse of gel dressings under high water content, insufficient antibacterial effect and imbalance in humidity regulation, the present invention uses PVA freeze-thaw physical network and alginate Ca / Zn composite ion network to synergistically confine pores to achieve stable forming; polyhexamethylene biguanide hydrochloride is made into chitosan / sodium tripolyphosphate microcapsules and coated with sodium alginate to construct a release sensitive to pH / ionic strength, which accelerates the inflammatory phase and self-limits in the later stage, and forms a long-term antibacterial effect through sustained release from SA-Zn sites; sodium carboxymethyl cellulose particles are combined with glycerol to establish a reversible water storage unit to maintain appropriate water activity, reduce immersion and dry stickiness; through the synergy of processes such as pre-encapsulation and low-shear incorporation with raw materials, stability and staged adaptation are highlighted.

[0005] The technical effects of the present invention are achieved through the following technical scheme: a gel dressing for skin wound repair, comprising the following raw materials in parts by weight: 65 to 75 parts of polyvinyl alcohol, 14 to 20 parts of sodium alginate, 4 to 8 parts of sodium carboxymethyl cellulose, 1 to 3 parts of sodium hyaluronate, 12 to 22 parts of glycerin, 1 to 3 parts of surface antifouling additives, 6 to 10 parts of antibacterial microcapsules and 2 to 2.8 parts of complex ions.

[0006] Preferably, the antifouling agent is any one of polyethylene glycol, povidone K30 and poloxamer F127; Preferably, the composite ion is composed of the following raw materials in parts by weight: 1.7 to 2.3 parts of CaCl2·2H2O and 0.3 to 0.5 parts of ZnCl2; Preferably, the antibacterial microcapsules are PHMB microcapsules, and the specific preparation steps are as follows: S1: chitosan was added to 0.5 wt% glacial acetic acid solution, stirred and dissolved until transparent, the pH of the solution was adjusted to 5.4-5.6 with NaOH solution, polyhexamethylene biguanide hydrochloride was slowly added to adjust the final concentration to 0.1-0.2 wt%, stirred at 300 rpm to disperse evenly, and vacuum degassing was performed; S2: Slowly spray the solution after treatment in step S1 into a 0.5wt% sodium tripolyphosphate solution, age it for 10-15 minutes, filter it, take out the particles, transfer them into 5 times the volume of 0.1wt% sodium alginate solution, gently stir for 3-5 minutes, centrifuge it at a low speed of 300-500g for 2-3 minutes, discard the supernatant, and wash it repeatedly with sterile water and isotonic saline for 3 times to obtain PHMB microcapsules; Preferably, in step S1, the ratio of the amount of chitosan to the glacial acetic acid solution is 0.5-1 g:100 mL; Preferably, in step S2, the amount of the sodium tripolyphosphate solution is 10 to 15 times the volume of the spray solution; Preferably, in step S2, the spray parameters are: pressure 0.1-0.2 MPa, liquid inlet 1-3 mL / min, spray distance 10-15 cm; Another aspect of the present invention is to provide a method for preparing a gel dressing for skin wound repair, which specifically comprises the following steps: S101: Heat deionized water in a water bath to 90°C, slowly add polyvinyl alcohol, stir until the solution is clear, cool to 45-55°C, sequentially add sodium alginate, sodium carboxymethyl cellulose, glycerin, sodium hyaluronate, and a surface antifouling agent, stir at 100-200 rpm to uniformly dissolve, vacuum degassing, and cool to 25-30°C to obtain a blend solution; S102: Slowly add PHMB microcapsules to the blended solution of step S101 in three batches, stir at 100-300 rpm to mix evenly, then add to a sterile support sheet, control the thickness to 2-4 mm with a spatula, and let it stand naturally to defoam until the surface is smooth; S103: placing the formed gel in step S102 in a low-temperature environment and subjecting it to a freeze-thaw cycle to obtain a cross-linked network system; immersing the cross-linked network system in a 20-30 times volume composite ion bath, gently shaking it at 50 rpm for 30-50 minutes, filtering it, taking it out and repeatedly washing it with sterile saline until no obvious free salt remains on the surface, thereby obtaining a gel dressing; Preferably, in step S103, the freeze-thaw cycle parameters are: pre-cooling at 4°C for 30 to 60 minutes; then freezing at -20°C for 12 hours and thawing at 25°C for 12 hours as one cycle, and a total of 3 to 5 cycles are performed; Preferably, in step S103, the composite ion bath is prepared by dissolving CaCl2·2H2O and ZnCl2 in deionized water.

[0007] The beneficial effects of the present invention are as follows: The present invention forms a technical effect of connecting the three dimensions of structural homeostasis, long-term antibacterial and phased adaptation by constructing a synergistic system of double network matrix, composite ion crosslinking and responsive antibacterial carrier, and systematically overcomes the problems of easy collapse, short antibacterial time and imbalance of humidity control of traditional gel dressing. First, the physical crystallization nodes formed by freeze-thaw induction of polyvinyl alcohol (PVA) and the coordination network constructed by alginate under the action of Ca / Zn composite ions are interconnected. The former provides energy dissipation and rebound, and the latter provides stiffness and resistance to rheological collapse. The two complement each other in terms of pore size and hydrophilicity, maintaining the fit between water vapor permeability and wound surface, and inhibiting the structural instability caused by high exudation and body temperature fluctuations. The Zn site introduced in the composite ion crosslinking has both coordination reinforcement and ion exchange sustained release functions. Through the ratio engineering with the Ca site, the mechanical homeostasis and functional ion flux are balanced in the same window, avoiding the uncontrollable swelling and release of the single crosslinking system in a hypertonic environment. In terms of antibacterial properties, polyhexamethylene biguanide hydrochloride (PHMB) microcapsules constructed from a polysaccharide-polyphosphate composite act as responsive carriers. Driven by endogenous signals such as alkalinity, increased ionic strength, and protein enrichment during the inflammatory phase, the pores reversibly expand, achieving early release to rapidly suppress the microbial load. As the wound environment returns to neutrality and low exudation, the carrier converges and the release rate becomes self-limited, reducing the risk of cell stimulation caused by peak concentrations. At the same time, the Zn sites in the alginate network generate a continuous and gentle flux through ion exchange, providing a stable antibacterial base for the middle and late stages. Sodium carboxymethyl cellulose (CMC-Na) particles dispersed in the pores act as reversible water storage units, preferentially absorbing water when exudate is abundant and slowly releasing it when exudate decreases. Combined with glycerol to reduce the evaporation rate, the water activity is maintained in a range that is conducive to cell migration and matrix synthesis, avoiding the alternation of the two extreme states of immersion and dry adhesion.

[0008] The process used in this invention involves freeze-thawing to solidify the physical crystals and pore framework, followed by a Ca / Zn composite ion bath to uniformly distribute the coordination crosslinks within the defined channels without over-density. The antimicrobial ingredients are pre-microencapsulated and incorporated under low-shear conditions to prevent network lock-in or inactivation during the freeze-thaw or ionic crosslinking stages. Subsequently, the product is gently rinsed and reconstituted with an isotonic medium to stabilize the initial surface ion environment and release starting point. This sequential arrangement reduces inter-material constraints, enabling a synergistic integration of mechanics, penetration, and release. The entire process utilizes aqueous, low-temperature preparation and conventional sterilization, avoiding complex chemical modifications and the need for high-energy equipment. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 Graph showing the biocompatibility test results of the gel dressings prepared in Examples 1 to 3 of the present invention and Comparative Examples 1 to 3; Figure 2 This is a graph showing the cumulative release of PHMB from the gel dressings prepared in Example 1 and Comparative Examples 1 to 3 of the present invention at pH 8.0; Figure 3 This is a graph showing the cumulative release of PHMB from the gel dressings prepared in Example 1 and Comparative Examples 1 to 3 of the present invention at pH 6.0; Figure 4 The Zn content of the gel dressing prepared in Example 1 and Comparative Examples 1 to 3 in the pH 8.0 group was 2+ Cumulative release result graph; Figure 5 The Zn content of the gel dressing prepared in Example 1 and Comparative Examples 1 to 3 in the pH 6.0 group was 2+ Cumulative release results graph. DETAILED DESCRIPTION

[0010] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, rather than all embodiments. Unless otherwise specified, the raw materials involved in the present invention are purchased through conventional commercial channels. Experimental methods without specific conditions are conventional methods and conventional conditions well known in the art, or are based on the conditions recommended by the instrument manufacturer.

[0011] Example 1: A gel dressing for skin wound repair, comprising the following raw materials in parts by weight: 75 parts of polyvinyl alcohol, 20 parts of sodium alginate, 4 parts of sodium carboxymethyl cellulose, 1 part of sodium hyaluronate, 22 parts of glycerol, 3 parts of surface antifouling agent, 10 parts of antibacterial microcapsules and 2.8 parts of complex ions.

[0012] The antibacterial microcapsules are PHMB microcapsules, and the specific preparation steps are as follows: S1: Add 2 g of chitosan to 200 mL of 0.5 wt% glacial acetic acid solution and stir until it becomes transparent. Adjust the pH to 5.4 with NaOH solution, slowly add polyhexamethylene biguanide hydrochloride to adjust its final concentration to 0.2 wt%, stir at 300 rpm to disperse evenly, and vacuum degas. S2: The solution treated in step S1 was slowly sprayed into 15 times the volume of 0.5 wt% sodium tripolyphosphate solution at a spray pressure of 0.2 MPa, a liquid feed of 1 mL / min, and a spray distance of 10 cm; the solution was aged for 15 minutes, filtered, and the particles were collected and transferred into 5 times the volume of 0.1 wt% sodium alginate solution, gently stirred for 5 minutes, and centrifuged at 500 g for 3 minutes. The supernatant was discarded and the solution was washed three times with sterile water and isotonic saline to obtain PHMB microcapsules; The preparation of the gel dressing for skin wound repair comprises the following steps: S101: Heat deionized water in a water bath to 90°C, slowly add polyvinyl alcohol, stir until the solution is clear, cool to 45°C, sequentially add sodium alginate, sodium carboxymethyl cellulose, glycerol, sodium hyaluronate, and povidone K30, stir at 200 rpm to dissolve evenly, vacuum degassing, and cool to 25°C to obtain a blend solution; S102: Slowly add PHMB microcapsules to the blended solution of step S101 in three batches, stir at 300 rpm to mix evenly, then add to a sterile support sheet, control the thickness to 2 mm with a spatula, and let it stand naturally to defoam until the surface is smooth; S103: The formed gel in step S102 is placed in a low-temperature environment and pre-cooled at 4°C for 60 minutes. Then, the gel is frozen at -20°C for 12 hours and thawed at 25°C for 12 hours, and a total of 5 cycles are performed to obtain a cross-linked network system. The cross-linked network system is immersed in a composite ion bath prepared by adding 30 times the volume of CaCl2·2H2O and ZnCl2 to deionized water, gently shaken at 50 rpm for 50 minutes, filtered, and repeatedly washed with sterile saline until no obvious free salt residue is left on the surface to obtain a gel dressing.

[0013] Example 2: A gel dressing for skin wound repair, comprising the following raw materials in parts by weight: 65 parts of polyvinyl alcohol, 14 parts of sodium alginate, 8 parts of sodium carboxymethyl cellulose, 3 parts of sodium hyaluronate, 12 parts of glycerol, 1 part of surface antifouling agent, 6 parts of antibacterial microcapsules and 2 parts of complex ions.

[0014] The composite ion is composed of the following raw materials in parts by weight: 1.7 parts of CaCl2·2H2O and 0.3 parts of ZnCl2; The antibacterial microcapsules are PHMB microcapsules, and the specific preparation steps are as follows: S1: Add 1 g of chitosan to 200 mL of 0.5 wt% glacial acetic acid solution and stir until it becomes transparent. Adjust the pH to 5.6 with NaOH solution, slowly add polyhexamethylene biguanide hydrochloride to adjust its final concentration to 0.1 wt%, stir at 300 rpm to disperse evenly, and vacuum degas. S2: The solution treated in step S1 was slowly sprayed into 10 volumes of 0.5 wt% sodium tripolyphosphate solution at a spray pressure of 0.1 MPa, a liquid feed of 3 mL / min, and a spray distance of 15 cm. The solution was aged for 10 minutes, filtered, and the particles were collected and transferred into 5 volumes of 0.1 wt% sodium alginate solution. The particles were gently stirred for 3 minutes, centrifuged at 300 g for 2 minutes, and the supernatant was discarded. The particles were washed three times with sterile water and isotonic saline to obtain PHMB microcapsules. The preparation of the gel dressing for skin wound repair comprises the following steps: S101: Heat deionized water in a water bath to 90°C, slowly add polyvinyl alcohol, stir until the solution is clear, cool to 55°C, add sodium alginate, sodium carboxymethyl cellulose, glycerol, sodium hyaluronate, and polyethylene glycol in sequence, stir at 100 rpm to uniformly dissolve, vacuum degassing, and cool to 30°C to obtain a blend solution; S102: Slowly add PHMB microcapsules to the blended solution of step S101 in three batches, stir at 100 rpm to mix evenly, then add to a sterile support sheet, control the thickness to 4 mm with a spatula, and let it stand naturally to defoam until the surface is smooth; S103: The formed gel in step S102 is placed in a low-temperature environment and pre-cooled at 4°C for 30 minutes. Then, the gel is frozen at -20°C for 12 hours and thawed at 25°C for 12 hours, and three cycles are performed to obtain a cross-linked network system. The cross-linked network system is immersed in a composite ion bath prepared by adding 20 times the volume of CaCl2·2H2O and ZnCl2 to deionized water, and gently shaken at 50 rpm for 30 minutes. The gel is filtered, taken out, and repeatedly washed with sterile saline until no obvious free salt residue is left on the surface to obtain a gel dressing.

[0015] Example 3: A gel dressing for skin wound repair, comprising the following raw materials in parts by weight: 70 parts of polyvinyl alcohol, 17 parts of sodium alginate, 6 parts of sodium carboxymethyl cellulose, 2 parts of sodium hyaluronate, 17 parts of glycerol, 2 parts of surface antifouling agent, 8 parts of antibacterial microcapsules and 2.4 parts of complex ions.

[0016] The composite ion is composed of the following raw materials in parts by weight: 2 parts of CaCl2·2H2O and 0.4 parts of ZnCl2; The antibacterial microcapsules are PHMB microcapsules, and the specific preparation steps are as follows: S1: Add 1.5 g of chitosan to 200 mL of 0.5 wt% glacial acetic acid solution and stir until it becomes transparent. Adjust the pH to 5.5 with NaOH solution, slowly add polyhexamethylene biguanide hydrochloride to adjust the final concentration to 0.15 wt%, stir at 300 rpm to disperse evenly, and vacuum degas. S2: The solution treated in step S1 was slowly sprayed into 12 times the volume of 0.5 wt% sodium tripolyphosphate solution at a spray pressure of 0.15 MPa, a liquid feed of 2 mL / min, and a spray distance of 12 cm; the solution was aged for 12 minutes, filtered, and the particles were collected and transferred into 5 times the volume of 0.1 wt% sodium alginate solution, gently stirred for 4 minutes, and centrifuged at a low speed of 400 g for 2.5 minutes. The supernatant was discarded and the solution was washed three times with sterile water and isotonic saline to obtain PHMB microcapsules; The preparation of the gel dressing for skin wound repair comprises the following steps: S101: Heat deionized water in a water bath to 90°C, slowly add polyvinyl alcohol, stir until the solution is clear, cool to 50°C, sequentially add sodium alginate, sodium carboxymethyl cellulose, glycerol, sodium hyaluronate, and povidone K30, stir at 150 rpm to dissolve evenly, vacuum degassing, and cool to 28°C to obtain a blend solution; S102: Slowly add PHMB microcapsules to the blended solution of step S101 in three batches, stir at 200 rpm to mix evenly, then add to a sterile support sheet, control the thickness to 3 mm with a spatula, and let it stand naturally to defoam until the surface is smooth; S103: The formed gel in step S102 is placed in a low-temperature environment and pre-cooled at 4°C for 45 minutes. Then, a cycle of freezing at -20°C for 12 hours and thawing at 25°C for 12 hours is performed for a total of 4 cycles to obtain a cross-linked network system. The cross-linked network system is immersed in a 25-fold volume of a composite ion bath prepared by adding CaCl2·2H2O and ZnCl2 to deionized water, and gently shaken at 50 rpm for 40 minutes. The gel is filtered, taken out, and repeatedly washed with sterile saline until no obvious free salt residue is left on the surface to obtain a gel dressing.

[0017] Comparative Example 1: The operating procedures of Comparative Example 1 and Example 1 are basically the same, the main difference being that in Comparative Example 1, the PHMB microcapsules are replaced with PHMB solution of the same effective dose for direct blending; the other operations remain unchanged.

[0018] Comparative Example 2: The operation process of Comparative Example 2 is basically the same as that of Example 1. The main difference is that in Comparative Example 2, a single Ca 2+ Crosslinking does not introduce Zn 2+ ; The rest of the operations remain unchanged.

[0019] Comparative Example 3: The operating procedures of Comparative Example 3 and Example 1 are basically the same, the main difference being that the freeze-thaw cycle treatment is cancelled in Comparative Example 3; the other operations remain unchanged.

[0020] Performance testing: Biocompatibility test: The gel dressings prepared in Examples 1 to 3 and Comparative Examples 1 to 3 were placed in a complete culture medium (DMEM + 10% fetal bovine serum + 1% penicillin-streptomycin) at a mass / volume ratio of 0.20 g / mL and extracted at 37 ° C with slight shaking for 24 h; the extract was sterilized by 0.22 μm filtration and set aside. CCK-8 cell viability detection and fluorescent live-dead staining were performed using fibroblasts. The negative control was a blank complete culture medium, and the positive control was a complete culture medium containing 10% DMSO. A cell-free blank well was set for background subtraction. The cell viability (%) was calculated as follows: (OD value of the embodiment - OD value of the negative control group) / (OD value of the negative control group - OD value of the positive control group) × 100%. Each batch of samples was tested three times independently, and the test results were averaged. The results are shown in the figure. Figure 1 shown.

[0021] based on Figure 1 The results show that the gel dressing prepared in the embodiment of the present invention has excellent biocompatibility and can be used effectively and safely. Based on the results of Example 1 and Comparative Example 1, the biocompatibility of Comparative Example 1 is significantly lower than that of the embodiment. This may be due to the peak precipitation of unencapsulated PHMB in the early stages of film formation / cross-linking and extraction, resulting in a high concentration of effective cationic polymer in the culture medium, inducing cell membrane damage and mitochondrial metabolism inhibition, and the occurrence of typical burst-type cytotoxicity. Based on the results of Example 1 and Comparative Example 2, the biocompatibility of Comparative Example 2 is moderately lower than that of the embodiment, which may be due to the removal of Zn 2+ After the functional sites, the alginate-Ca network is more susceptible to ion exchange softening in an isotonic environment, and trace polysaccharide / oligomer residues and Ca 2+ Migration causes the extract composition to deviate from the optimal window; at the same time, low-level Zn is missing 2+ The cell adhesion and barrier repair support effect leads to poor compatibility. Based on the analysis of the results of Example 1 and Comparative Example 3, the survival rate of Comparative Example 3 is significantly lower than that of the Example. This may be due to the lack of the PVA freeze-thaw physical crystallization network, which makes the pores more loosely connected, making it easier for small molecules and ions to be extracted in the early stage. The localized shelling and microscopic defects caused by the Ca / Zn surface cross-linking gradient form a higher initial dissolution burden and a significant decrease in survival rate.

[0022] Release kinetics test: The gel dressings prepared in Example 1 and Comparative Examples 1 to 3 were cut into discs with a diameter of 25 mm and a thickness of 3 mm and placed in a pH 8.0 group (HEPES 10 mM + NaCl 140 mM + 0.02% NaN3 + 2% human serum albumin) and a pH 6.0 group (MES 10 mM + NaCl 140 mM + 0.02% NaN3); volume 100 mL, temperature 32 ° C, horizontal shaker 60 rpm, container polypropylene bottle, pH 8.0 group and pH 6.0 group were set up with blank controls (same volume of medium, no sample), and samples were taken at 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h and 120 h, each sampling 2 mL, and an equal volume of fresh medium at the same temperature was added to replenish immediately. After sampling, they were immediately divided (the same batch was tested independently): one part for PHMB and one part for Zn 2+ , prepare a series of PHMB standards (0, 1, 2, 5, 10, 15, 20 mg / L) using the same buffer system (HEPES / MES), select the main absorption peak of λ = 235-238 nm to establish a calibration curve; the sample to be tested is filtered once through 0.22 μm PES, the absorbance is measured at the same λ, and the concentration is converted using the calibration curve. The results are as follows Figure 2 and Figure 3 As shown; Each sample of Zn was immediately acidified to 2% (v / v) with ultrapure HNO3 to prevent hydrolysis, precipitation or adsorption. A Zn standard series (0, 0.01, 0.05, 0.1, 0.2, 0.5, 1 mg / L) was prepared with the same acidity matrix. The concentration was measured and converted on the machine. The results are shown as follows Figure 4 and Figure 5 As shown; the above PHMB and Zn 2+ The cumulative release is calculated as follows: Cumulative release amount at time n (mg) = M n-1 +V0(C n -C n-1 )+V s *C n-1 ; where M n-1 is the cumulative release amount of the n-1th time, V0 is the total volume of the dissolution medium (replenished to this volume after each sampling), V s is the sampling volume of each equal volume, C n-1 and C n When sampling for the n-1th or nth time, the concentration of the analyte (PHMB or Zn 2+ concentration).

[0023] based on Figure 2 、 Figure 3 and Figure 4 、 Figure 5 The results show that the gel dressing prepared in the embodiment effectively achieves the effect of PHMB and Zn2+ The release of PHMB in both pH 6.0 and 8.0 environments simultaneously meets the requirements of early antibacterial effect and low flux maintenance in the middle and late stages, avoiding the occurrence of explosive release driven by free diffusion or fluctuations due to structural instability; based on the analysis of the results of Comparative Example 1 and Example 1, the early cumulative release of PHMB in Comparative Example 1 is significantly higher than that in Example 1, and then decays faster in the middle and late stages; this may be due to the lack of pore gating that can respond to microcapsules. PHMB is more likely to enter the interconnected aqueous phase channels and accumulate on the surface during film formation, freeze-thaw and ion cross-linking, forming an initial burst dominated by free diffusion; at the same time, free PHMB is easily electrostatically associated with the carboxyl groups of alginate and partially adsorbed and retained by the protein layer, which is particularly obvious in the pH 8.0 and protein environment, resulting in the rapid depletion of free components that can be released in the later stage, and the cumulative curve enters the plateau phase. Based on the analysis of the results of Comparative Example 2 and Example 1, the cumulative release trajectory of PHMB in Comparative Example 2 is similar to that of Example 1 in the early stage, but Zn 2+ The curve approaches zero and lacks visible flux at a later stage; this may be due to the fact that only Ca 2+ The cross-linking lacks Zn sites, and the system does not have a functional ion exchange extravasation channel. Therefore, it can only rely on the self-limiting release of the microcapsules. After entering the middle and late stages, there is a lack of ion base support, and the cumulative curve slows down faster. At the same time, the Ca-SA network is in an isotonic or even alkaline environment with Na + Substitution softening is more likely to occur, and the pore stability and flux controllability decrease, resulting in small fluctuations in the later period. Based on the analysis of the results of Comparative Example 3 and Example 1, Comparative Example 3 shows higher PHMB and Zn in the early stage. 2+ The cumulative release slowed down significantly in the middle and late stages. This may be due to the lack of a physical crystallization network formed by freeze-thaw of PVA, which resulted in larger matrix pores and higher connectivity. Ionic crosslinking easily formed a gradient on the surface, thinning the diffusion boundary layer and accelerating the initial exudation. Microcapsules were more likely to deform or develop microcracks in the shell in the absence of skeleton support, amplifying the initial flux. However, with the dissipation of the releasable components and the gradual hydration and rearrangement of the network, the flux entered a low-slope platform in the later stage, making it difficult to maintain a stable effective flux.

[0024] Antibacterial test: The gel dressings prepared in Example 1 and Comparative Examples 1 to 3 were cut into discs with a diameter of 25 mm and a thickness of 2 mm. 100 μL of the target bacterial suspension (10 6CFU / mL Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), covered with a sterilized film to spread evenly, placed in a sealed humidified box (RH ≥ 90%), and incubated at 35°C for 24h, 48h and 72h. At that time, the sample together with the film was placed in a pre-cooled neutralizer (broth medium + 3% Tween-80 + 0.3% lecithin + 0.1% histidine + 0.5% sodium thiosulfate), vortexed vigorously for 60s and then sonicated for 1min (40kHz) to dissociate the remaining bacteria, coated on TSA plates, incubated at 35°C for 48h, and CFU was counted. The percentage of bacterial reduction (%) was calculated as (bacterial CFU before inoculation - bacterial CFU after inoculation) / bacterial CFU before inoculation × 100%. The results are shown in Table 1 below.

[0025] Table 1. Antibacterial test results of gel dressing

[0026] Based on the results in Table 1, the examples of the present invention showed high onset and stable bactericidal effects against the three bacteria, with a bactericidal rate of more than 99% maintained for 72 hours. This can be attributed to the fact that the microcapsules provided sufficient PHMB in the early stage to quickly inhibit the growth of the bacteria, and then the Zn 2+ The sustained-release site maintains low-flux antibacterial properties; the PVA freeze-thaw dual network stabilizes the pores and permeability window, effectively avoiding peak overshoot and late attenuation. Based on the analysis of the results of Comparative Example 1 and Example 1, the 24h sterilization rate of Comparative Example 1 is high, but it drops significantly from 48 to 72h. This may be due to the rapid depletion of the active ingredients caused by the initial burst release and the lack of maintenance in the later period; at the same time, the protein / polyanion components are easily inactivated by the association with PHMB; Based on the analysis of the results of Comparative Example 2 and Example 1, the sterilization rate of Comparative Example 2 is close to that of the example in 24h, but it continues to decline from 48 to 72h. This may be due to the fact that it is mainly driven by the PHMB pathway in the early stage and the elimination of Zn 2+ After the functional site, the antibacterial base is lost in the later stage, and re-contamination / biofilm regeneration is more likely to occur; based on the analysis of the results of Comparative Example 3 and Example 1, Comparative Example 3 has no freeze-thaw, and the overall performance is lower than that of the example and the intra-batch fluctuation is large. It lacks the PVA physical crystallization network shaping, and the pores are more loosely connected. Although the dissolution is fast in the early stage, it is difficult to control. In the later stage, the softening of the structure and the cross-linking gradient lead to poor maintenance and unevenness.

[0027] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A gel dressing for skin wound repair, characterized in that: The composition includes the following raw materials in parts by weight: 65-75 parts of polyvinyl alcohol, 14-20 parts of sodium alginate, 4-8 parts of sodium carboxymethyl cellulose, 1-3 parts of sodium hyaluronate, 12-22 parts of glycerin, 1-3 parts of surface antifouling additives, 6-10 parts of antibacterial microcapsules and 2-2.8 parts of complex ions.

2. The gel dressing for skin wound repair according to claim 1, characterized in that: The anti-fouling auxiliary agent is any one of polyethylene glycol, povidone K30 and poloxamer F127.

3. The gel dressing for skin wound repair according to claim 2, characterized in that: The composite ion is composed of the following raw materials in parts by weight: 1.7 to 2.3 parts of CaCl2·2H2O and 0.3 to 0.5 parts of ZnCl2.

4. The gel dressing for skin wound repair according to claim 3, characterized in that: The antibacterial microcapsules are PHMB microcapsules, and the specific preparation steps are as follows: S1: Add chitosan to glacial acetic acid solution, stir and dissolve until transparent, adjust the pH with NaOH solution, slowly add polyhexamethylene biguanide hydrochloride, stir and disperse evenly, and vacuum degas; S2: The solution treated in step S1 is slowly sprayed into a sodium tripolyphosphate solution, aged, filtered, and the particles are taken and transferred into a sodium alginate solution. The mixture is gently stirred and centrifuged at a low speed. The supernatant is discarded and the mixture is repeatedly washed with sterile water and isotonic saline to obtain PHMB microcapsules.

5. The gel dressing for skin wound repair according to claim 4, characterized in that: In step S1, the ratio of the chitosan to the glacial acetic acid solution is 0.5-1 g:100 mL.

6. The gel dressing for skin wound repair according to claim 5, characterized in that: In step S2, the amount of the sodium tripolyphosphate solution used is 10 to 15 times the volume of the spray solution.

7. The gel dressing for skin wound repair according to claim 6, characterized in that: In step S2, the spray parameters are: pressure 0.1-0.2 MPa, liquid inlet 1-3 mL / min, and spray distance 10-15 cm.

8. A method for preparing a gel dressing for skin wound repair according to any one of claims 1 to 7, characterized in that: The specific steps include: S101: Heat deionized water in a water bath, slowly add polyvinyl alcohol, stir until the solution is clear, cool, sequentially add sodium alginate, sodium carboxymethyl cellulose, glycerin, sodium hyaluronate, and a surface antifouling agent, stir to dissolve evenly, perform vacuum degassing, and cool to obtain a blend solution; S102: Slowly add PHMB microcapsules to the blended solution of step S101 in three batches, stir and mix evenly, then add to a sterile support sheet, control the thickness with a spatula, and let it stand naturally to defoam until the surface is smooth; S103: placing the formed gel in step S102 in a low-temperature environment, and subjecting it to freeze-thaw cycles to obtain a cross-linked network system; immersing the cross-linked network system in a composite ion bath, gently shaking, filtering, taking it out, and repeatedly washing it with sterile saline until no obvious free salt remains on the surface, thereby obtaining a gel dressing.

9. A method for preparing the gel dressing for skin wound repair according to claim 8, characterized in that: In step S103, the freeze-thaw cycle parameters are: pre-cooling at 4°C for 30 to 60 minutes; then freezing at -20°C for 12 hours and thawing at 25°C for 12 hours as one cycle, and a total of 3 to 5 cycles are performed.

10. A method for preparing the gel dressing for skin wound repair according to claim 9, characterized in that: In step S103, the composite ion bath is prepared by dissolving CaCl2.2H2O and ZnCl2 in deionized water.

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