Gel for promoting wound healing and preparation method thereof

Abstract

The invention relates to the technical field of biological medicine, in particular to a gel for promoting wound healing and a preparation method thereof, and the preparation method comprises the following steps: S1, preparing superabsorbent polymer microspheres as an absorption core; s2, performing surface functionalization treatment, and wrapping an intelligent film layer to form a packaging super-absorption core; s3, dissolving chitosan and carboxymethyl chitosan in an alkaline solution to obtain an alkaline polysaccharide mixed solution; step S4, adding oxidized regenerated cellulose in batches while stirring; s5, after all the oxidized regenerated cellulose is added, detecting the energy storage modulus and the loss modulus through a rheometer, and judging a gelation starting point; s6, judging whether embedding of the active factors is completed or not to obtain carrier gel; step S7, adding a rhizoma bletillae polysaccharide solution to obtain composite gel; step S8, adding rhizoma bletillae plant essential oil, emulsifying and dispersing, and standing and curing at low temperature to obtain the rhizoma bletillae compound gel. According to the invention, the interstitial fluid adsorption capacity of the gel and the accurate release of the healing agent are improved.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a gel that promotes wound healing and its preparation method. Background Technology

[0002] Skin wound healing is a highly complex and ordered biological process involving multiple stages such as hemostasis, inflammation, proliferation, and remodeling. An ideal wound dressing not only needs to provide a physical barrier, absorb exudate, and maintain a moist environment, but also should be able to dynamically respond to the complex changes in the wound microenvironment and actively regulate its function to promote healing. The microenvironment of chronic, difficult-to-heal wounds (such as diabetic foot ulcers, pressure ulcers, and venous ulcers) typically exhibits abnormal biomarkers, such as persistent acidic pH, excessive proteases (e.g., matrix metalloproteinases, MMPs), high levels of reactive oxygen species (ROS), and abnormal ion concentrations. Traditional passive dressings (such as gauze, sponges, and ordinary hydrogels) struggle to cope with this dynamic imbalance, often leading to delayed healing, increased risk of infection, and secondary damage from frequent dressing changes.

[0003] Hydrogels are considered ideal wound dressing substrates due to their high water content, good biocompatibility, and tunable physicochemical properties. However, chemically cross-linked hydrogel dressings have poor spreadability, and the chemical cross-linking agents used have certain cytotoxicity. Polysaccharides are natural macromolecules that are widely available and possess biological activity, biocompatibility, and low or no cytotoxicity. Hydrogels prepared by physical cross-linking methods can avoid the use of toxic cross-linking agents. Therefore, polysaccharide hydrogels are an economical, green, and safe product, and there are numerous reports in the existing technology regarding the use of natural polysaccharide-based hydrogels such as chitosan, hyaluronic acid, and sodium alginate for wound repair.

[0004] Chinese Patent Publication No. CN109776819A discloses a Bletilla striata polysaccharide-carboxymethyl chitosan composite hydrogel and its preparation. The preparation mainly includes: first, preparing a Bletilla striata polysaccharide solution and a carboxymethyl chitosan solution; mixing the carboxymethyl chitosan solution with fully swollen carbomer 940 at a certain ratio; adjusting the pH of the gel system with triethanolamine; then adding a certain amount of Bletilla striata polysaccharide solution and deionized water; and stirring thoroughly to obtain the composite polysaccharide hydrogel. The prepared Bletilla striata polysaccharide-carboxymethyl chitosan composite hydrogel is formed through hydrogen bond physical cross-linking, possessing a porous and amorphous structure. Its rheological properties exhibit solid-state elasticity, good water retention, and good biocompatibility, showing a significant repair effect on wound damage.

[0005] Chinese Patent Publication No. CN120168702A discloses a Bletilla striata polysaccharide gel patch for wound repair and its preparation method. In preparing the Bletilla striata polysaccharide gel patch for wound repair, graphene oxide is reacted sequentially with 3-methylaminopropylamine and 4-(N-maleimidemethyl)cyclohexane-1-carboxylic acid succinimide ester to obtain modified graphene oxide; Bletilla striata polysaccharide is extracted from Bletilla striata, and then reacted sequentially with maleic anhydride and N-methyldopamine to obtain modified Bletilla striata polysaccharide; the modified Bletilla striata polysaccharide and modified graphene oxide are reacted with 1,5-dibromopentane, mixed with deionized water, coated, and film-formed to obtain the Bletilla striata polysaccharide gel patch for wound repair. The Bletilla striata polysaccharide gel patch for wound repair prepared by this invention has antibacterial, high adhesion, and antioxidant capabilities.

[0006] Chinese Patent Publication No. CN120324333A discloses a Bletilla striata polysaccharide hydrogel, its preparation method, and its uses. By screening the types, amounts, and preparation processes of each component in the gel, this invention prepares a BSP-MA / HA-NB hydrogel, which includes methacryloylated Bletilla striata polysaccharide, o-nitrosobenzaldehyde-modified hyaluronic acid, and other raw materials. The hydrogel exhibits significantly improved adhesion and mechanical properties; it achieves a long-lasting sustained-release effect of the drug components, promotes the proliferation activity and migration ability of bone marrow mesenchymal stem cells, and shows promising application prospects in the treatment and repair of bone defects.

[0007] Therefore, the aforementioned Bletilla striata polysaccharide-carboxymethyl chitosan composite hydrogel and its preparation, Bletilla striata polysaccharide gel patch for wound repair and its preparation method, as well as the Bletilla striata polysaccharide hydrogel and its preparation method and applications, have the following problems: their functional mechanisms are mostly passive responses, unable to achieve intelligent management of exudate and on-demand drug release in response to dynamic changes in the wound microenvironment (such as pH, specific enzyme concentration); the preparation process mostly relies on fixed parameters, lacking real-time monitoring and dynamic control of key intermediate states (such as viscosity, gelation process), resulting in poor performance consistency between batches of products; the loading of active ingredients (especially easily inactivated biological factors) mostly adopts simple blending methods, lacking effective activity protection and spatiotemporal controlled release strategies; and it fails to integrate the intelligent response core, the stable carrier constructed by the adaptive process, the fusion of multiple active networks, and the process closed-loop quality verification system, making it difficult to meet the multiple complex needs of high-exudation, easily infected chronic wounds for rapid exudate absorption, long-lasting antibacterial effect, precise healing promotion, and good biocompatibility. Summary of the Invention

[0008] Therefore, the present invention provides a gel that promotes wound healing and a method for preparing the same, in order to overcome the problems of passive functional mechanism, lack of intelligent response capability to wound microenvironment, fixed preparation process, and poor product performance consistency of existing wound dressing gels.

[0009] To achieve the above objectives, the present invention provides a gel for promoting wound healing and a method for preparing the same, comprising: Step S1: Prepare superabsorbent polymer microspheres as absorption cores; The polymer is selected from one or more of sodium polyacrylate, starch-grafted acrylate, and sodium carboxymethyl cellulose. Step S2: Perform surface functionalization treatment on the superabsorbent polymer microspheres, coat them with a smart film layer that is sensitive to biomarkers of the wound microenvironment to form an encapsulated superabsorbent core, and verify the smart response characteristics of the encapsulated superabsorbent core. Step S3: Dissolve chitosan and carboxymethyl chitosan in an alkaline solution and stir continuously until a homogeneous, clear or slightly opalescent viscous solution is formed, thus obtaining an alkaline polysaccharide mixture. Step S4: Obtain the alkaline polysaccharide mixture, add oxidized regenerated cellulose in portions while stirring, monitor the system viscosity in real time, and dynamically adjust the addition rate and stirring rate of oxidized regenerated cellulose based on the system viscosity value to keep the system viscosity within a preset range to ensure uniform dispersion. Step S5: After all the oxidized regenerated cellulose has been added, the storage modulus and loss modulus are detected by rheometer to determine the starting point of gelation, and the gelation state is determined based on the growth rate of the storage modulus to obtain a carrier substrate gel solution with a preliminary three-dimensional network. Step S6: Obtain the carrier substrate gel solution. Based on the gelation state and the verification results of encapsulating the superabsorbent core, adaptively select the active ingredient loading strategy. By monitoring the dispersion uniformity index of the mixed system, determine whether the active factor has been completely encapsulated. After completion, allow the network to stabilize at low temperature to obtain the carrier gel. Step S7: Obtain the carrier gel, add Bletilla striata polysaccharide solution, and fuse at a constant temperature; monitor the change in system viscosity, and when the viscosity reaches its peak and enters the plateau period, it is determined that the fusion of Bletilla striata polysaccharide network is complete, and a composite gel is obtained; Step S8: Obtain the composite gel, add Bletilla striata plant essential oil, and emulsify and disperse it; after determining by microscopic observation that the essential oil has reached the preset micro-dispersion standard, stop emulsification, and let it stand at low temperature to solidify, thereby obtaining the Bletilla striata compound gel.

[0010] Further, step S2 includes: Step S21: Disperse the superabsorbent polymer microspheres in a solvent, remove surface impurities by washing, and activate their surface by plasma treatment to enhance surface energy or introduce active functional groups to obtain activated superabsorbent polymer microspheres. Step S22: Determine the concentration of the smart film-forming polymer with specific responsiveness based on the pH value of the target wound; Step S23: Mix the activated polymer microspheres with the smart film-forming polymer solution, and use layer-by-layer self-assembly, interfacial polymerization, co-precipitation or microfluidic coating technology to form a uniform pre-coating layer on the surface of the microspheres. Step S24: The pre-coating layer is subjected to chemical cross-linking, photocuring or thermal curing to form a structurally stable smart film layer, thereby obtaining an encapsulated superabsorbent core. Step S25: Obtain the encapsulated superabsorbent core, place it in a solution simulating the presence of the target biomarker, and verify the intelligent response characteristics.

[0011] Further, step S25 includes: Step S251: The encapsulated superabsorbent core sample is placed in a first solution simulating a normal healing environment and a second solution simulating the abnormal presence of the target biomarker, respectively. S252: Real-time monitoring and recording of swelling kinetics data for two groups of samples within a preset time period; S253: Based on monitoring data, calculate the half-maximum response time and response intensity ratio of the encapsulated superabsorbent core in the second solution; The half-maximum response time is the time required from contact with the second solution until its swelling degree reaches 50% of the maximum equilibrium swelling degree in the solution; The response intensity ratio R is the ratio of the maximum equilibrium swelling degree in the second solution to the maximum equilibrium swelling degree in the first solution; S254: Compare the calculated half-maximum response time and R value with a preset qualified threshold to determine whether the smart response characteristics of the encapsulated superabsorbent core have been verified.

[0012] Furthermore, in step S254, if the verification of the smart response characteristics of the encapsulated superabsorbent core fails, an adjustment instruction is generated based on the exceeding of the half-maximum response time and response intensity ratio. If the half-maximum response time exceeds the standard while the response intensity ratio meets the standard, it is diagnosed as "slow response dynamics". In this case, the thickness of the smart film layer should be reduced or the porosity of the encapsulated superabsorbent core should be increased. If the response intensity ratio is not up to standard but the half-maximum response time is up to standard, it is diagnosed as "insufficient response thermodynamics", and the proportion of responsive functional groups in the smart film-forming polymer is increased. If both the half-maximum response time and the response intensity ratio fail to meet the standards, it is diagnosed as a "comprehensive failure". In this case, the proportion of responsive functional groups in the smart film-forming polymer is increased and the porosity of the encapsulated superabsorbent core is improved.

[0013] Further, in step S6, based on the gelation state and the verification results of the encapsulated superabsorbent core, an adaptive selection of the active ingredient loading strategy is made, including: The gelation state is determined based on the comparison between the growth rate of the energy storage modulus and the first preset threshold and the second preset threshold. If the growth rate of the energy storage modulus is greater than the second preset threshold and less than or equal to the first preset threshold, it is determined to be in a "equilibrium gel state". If the growth rate of the energy storage modulus is less than or equal to the second preset threshold, it is determined to be a "dense gel state"; For "equilibrium gel state" or "dense gel state", a strategy is adopted to preload human epidermal growth factor onto part of the surface of the encapsulated superabsorbent core and then mix it in as a whole, in order to protect the activity of the factor and achieve targeted release.

[0014] Furthermore, human epidermal growth factor is preloaded onto the surface of a partially encapsulated superabsorbent core, including: Step S61: Human epidermal growth factor is dissolved in a physiologically compatible buffer solution to obtain an active factor loading solution. Step S62: Immerse the encapsulated superabsorbent core in the active factor loading solution and incubate it under the condition of maintaining the biological activity of human epidermal growth factor, so that the human epidermal growth factor is adsorbed onto the surface of the encapsulated superabsorbent core through non-covalent interaction to obtain the mixed system. Step S63: After incubation, the encapsulated superabsorbent core that has completed surface adsorption is separated from the remaining liquid to obtain a functionalized absorbent core with human epidermal growth factor preloaded on the surface.

[0015] Furthermore, the dispersion uniformity index of the mixed system includes one or more of the following: turbidity of the mixed solution, transmittance, or coefficient of variation of the zeta potential. Determining whether the active ingredient has been successfully encapsulated includes: If the rate of change of turbidity or transmittance drops below a preset threshold and remains stable, or the coefficient of variation of the zeta potential drops below a preset threshold and remains stable, then the encapsulation of the active factor is considered complete.

[0016] Further, step S7 includes: Step S71: Under constant temperature and continuous stirring, add the Bletilla striata polysaccharide solution to the carrier gel, and simultaneously start continuous monitoring of the viscosity of the system; Step S72: Based on the viscosity monitoring data, plot the viscosity-time curve and calculate the instantaneous rate of change of viscosity in real time; Step S73: When the instantaneous rate of change of viscosity changes from a positive value to a negative value for the first time, continue monitoring. When the viscosity data enters and remains within a stable fluctuation range, it is determined that the fusion of Bletilla striata polysaccharide network is complete.

[0017] The stable fluctuation range refers to the relative deviation of at least three consecutive viscosity measurements not exceeding a preset threshold.

[0018] Further, step S8 includes: Step S81: Slowly add Bletilla striata plant essential oil to the composite gel and apply a first horizontal shear force for initial dispersion to obtain a first dispersion. Step S82: Obtain the first dispersion, apply a second horizontal shear force for fine dispersion, and obtain the second dispersion; Step S83: Obtain the particle size distribution data of essential oil droplets in the second dispersion. When the particle size distribution data simultaneously meets the preset upper limit of particle size and the distribution uniformity standard, and remains stable, it is determined that the emulsification and dispersion is complete.

[0019] On the other hand, the present invention also provides a wound-healing gel prepared by the method for preparing the wound-healing gel, for use in dressings for managing highly exudative or easily infected chronic wounds.

[0020] Compared with the prior art, the beneficial effects of the present invention are that by constructing a wound healing gel system that integrates intelligent responsive microspheres, an adaptive process control system, and multiple functional networks, the entire process from raw material processing, intelligent core preparation, carrier construction to active ingredient loading is optimized and controlled. This systematically solves the problems of passive function, crude process, insufficient activity protection, and low integration in the prior art, and significantly improves the level of intelligence and treatment effect of chronic wound management.

[0021] Furthermore, the gel of this invention possesses intelligent responsiveness and on-demand functional regulation capabilities tailored to the wound microenvironment. By constructing a superabsorbent core encapsulated in an intelligent membrane layer sensitive to specific biomarkers (such as pH, proteases, reactive oxygen species, and metal ions), the gel can rapidly respond and undergo significant swelling or structural changes upon contact with abnormal wound exudate. This not only achieves intelligent absorption and management of exudate but also triggers the precise release of internally loaded therapeutic factors (such as growth factors) when needed, fundamentally overcoming the problems of passive functional mechanisms and inability to adapt to the dynamic wound microenvironment in existing technologies.

[0022] Furthermore, the preparation method of this invention constructs a closed-loop, adaptive intelligent process system, ensuring high consistency and reliability of product performance. By introducing real-time monitoring and feedback control of viscosity, rheological parameters, etc., it replaces the traditional fixed parameter operation. This greatly solves the defects of existing technologies, such as large batch-to-batch performance fluctuations caused by fixed processes and open-loop operation.

[0023] Furthermore, this invention provides an adaptive active ingredient loading strategy based on carrier structure and function verification results, effectively protecting sensitive factors and achieving their efficient utilization. Based on the real-time "gelling state" of the carrier gel and the verification results of the intelligent core, the system automatically selects the optimal active factor loading method. This differentiated loading method not only maximizes the protection of the activity of biological factors and avoids inactivation caused by simple mixing, but also achieves precise positioning and controllable release of factors within the gel, significantly improving bioavailability and therapeutic efficacy.

[0024] Furthermore, this invention integrates a smart response core, adaptive processes, and multiple active networks to form a synergistic and comprehensive chronic wound management solution. This invention is not simply a matter of piling up components, but rather a systematic integration of a smart absorption and release core, a multiple active gel network constructed from chitosan / Bletilla striata polysaccharides, and a robust preparation process based on real-time feedback. The final product simultaneously provides multiple functions, including rapid and intelligent fluid absorption, long-lasting antibacterial and anti-inflammatory effects, continuous promotion of cell proliferation and migration, and excellent biocompatibility. Its performance is uniform and stable, making it particularly suitable for treating chronic wounds with high exudation, susceptibility to infection, and difficulty in healing, thus meeting the multiple and complex clinical needs for high-end dressings. Attached Figure Description

[0025] Figure 1 This is a flowchart of the preparation method of the wound-healing gel of the present invention; Figure 2 This is a flowchart of step S2 in the preparation method of the wound-healing gel of the present invention; Figure 3 This is a flowchart of step S6 in the method for preparing the wound-healing gel of the present invention; Figure 4 This is a flowchart of step S7 in the method for preparing the wound-healing gel of the present invention; Figure 5 This is a flowchart of step S8 in the method for preparing the wound-healing gel of the present invention. Detailed Implementation

[0026] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0027] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0028] It should be noted that in the description of this invention, the terms "upper", "lower", "left", "right", "inner", "outer", etc., which indicate directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings. This is only for the convenience of description and is not intended to indicate or imply that the device or element must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation of this invention.

[0029] Furthermore, it should be noted that, in the description of this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances. Implementation: 1:

[0030] Please see Figure 1 The diagram shows a flowchart of the preparation method of the wound-healing gel of the present invention, comprising: Step S1: Prepare superabsorbent polymer microspheres as absorption cores; The polymer is selected from one or more of sodium polyacrylate, starch-grafted acrylate, and sodium carboxymethyl cellulose. Specifically, 100 g of acrylic acid was weighed and neutralized to a 75% molar ratio with 30% NaOH solution. 1.5 g of crosslinking agent N,N'-methylenebisacrylamide and 0.5 g of initiator ammonium persulfate were added. The aqueous phase was then added to an oil phase containing 500 mL of cyclohexane and 10 g of Span-80. The reaction was carried out at 60°C, 500 rpm, and under nitrogen protection for 4 hours. After centrifugation, the microspheres were washed successively with ethanol and water, vacuum dried at 60°C for 24 hours, and sieved to obtain microspheres with a particle size of 50-200 micrometers. The water absorption ratio in physiological saline was measured to be 550 g / g, yielding superabsorbent polymer microspheres.

[0031] Step S2: Perform surface functionalization treatment on the superabsorbent polymer microspheres, coat them with a smart film layer that is sensitive to biomarkers of the wound microenvironment to form an encapsulated superabsorbent core, and verify the smart response characteristics of the encapsulated superabsorbent core. Specifically, step S2 includes: Step S21: Disperse the superabsorbent polymer microspheres in a solvent, remove surface impurities by washing, and activate their surface by plasma treatment to enhance surface energy or introduce active functional groups to obtain activated superabsorbent polymer microspheres. Step S22: Determine the concentration of the smart film-forming polymer with specific responsiveness based on the pH value of the target wound; select the smart film-forming polymer with specific responsiveness based on the chemical characteristics of the target wound biomarkers. The biomarkers include specific pH values, specific protease concentrations, specific reactive oxygen species concentrations, or specific metal ion concentrations. Step S23: Mix the activated polymer microspheres with the smart film-forming polymer solution to form a uniform pre-coating layer on the surface of the microspheres; Step S24: The pre-coating layer is cured to form a structurally stable smart film layer, thereby obtaining the encapsulated superabsorbent core; Step S25: Obtain the encapsulated superabsorbent core, place it in a solution simulating the presence of the target biomarker, and verify the intelligent response characteristics.

[0032] Specifically, the microspheres obtained in step S1 were dispersed in anhydrous ethanol and ultrasonically cleaned for 10 minutes. The supernatant was removed by centrifugation, and this process was repeated three times to remove surface impurities. Subsequently, the surface of the microspheres was activated by low-temperature oxygen plasma treatment (100W power, 2 minutes) to obtain activated superabsorbent polymer microspheres.

[0033] To address the alkaline microenvironment (pH 7.5–8.5) commonly found in chronic wounds and the microenvironment characteristics of normal skin fluids (pH 5.4–5.9), sodium alginate was selected as a pH-sensitive smart film-forming polymer. A 1.5% (w / v) sodium alginate aqueous solution was prepared. Activated microspheres were added to the sodium alginate solution and slowly stirred for 5 minutes to ensure the microsphere surface was fully wetted and reached a stable pre-swelled state. This facilitated the uniform adsorption and coating of sodium alginate on the microsphere surface while preventing excessive swelling of the microspheres.

[0034] It is understood that the concentration is determined based on the concentration-response relationship established by preliminary experiments. These preliminary experiments involve preparing smart film-forming polymer solutions of different concentrations and testing their response intensity ratio and half-maximum response time, with the lowest concentration that simultaneously meets the response intensity and response speed requirements being selected as the standard.

[0035] Subsequently, the mixture containing microspheres is passed through a microfluidic device, wherein the aqueous phase of the microfluidic device is a sodium alginate-microsphere mixture and the oil phase is liquid paraffin, forming droplets and collecting them in a curing bath containing 2% w / v calcium chloride to form a calcium alginate pre-coating layer.

[0036] The coated microspheres were washed with deionized water and then immersed in phosphate buffer containing 0.5% w / v genipin for cross-linking at 37°C for 6 hours to enhance membrane stability. After centrifugation, washing, and lyophilization, the encapsulated superabsorbent core was obtained. Its intelligent response characteristics were then verified.

[0037] Specifically, step S25 includes: Step S251: The encapsulated superabsorbent core sample is placed in a first solution simulating a normal healing environment and a second solution simulating the abnormal presence of the target biomarker, respectively. S252: Real-time monitoring and recording of swelling kinetics data for two groups of samples within a preset time period; S253: Based on monitoring data, calculate the half-maximum response time and response intensity ratio of the encapsulated superabsorbent core in the second solution; Wherein, the half-maximum response time is the time required from contact with the second solution until its swelling degree reaches 50% of the maximum equilibrium swelling degree in the solution, and the response intensity ratio R is the ratio of the maximum equilibrium swelling degree in the second solution to the maximum equilibrium swelling degree in the first solution; S254: Compare the calculated half-maximum response time and R value with a preset qualified threshold to determine whether the smart response characteristics of the encapsulated superabsorbent core have been verified.

[0038] Specifically, the smart response characteristics of the packaged superabsorbent core are deemed to have passed verification if and only if the half maximum response time is less than or equal to the preset qualified response time and the response intensity ratio is greater than or equal to the preset qualified response intensity ratio. If the half-maximum response time is greater than the preset qualified response time or the response intensity ratio is less than the preset qualified response intensity ratio, then the verification of the intelligent response characteristics of the packaged superabsorption core is deemed to have failed.

[0039] In this embodiment, step S254 further includes generating an adjustment instruction based on the exceeding of the half-maximum response time and response intensity ratio if the smart response characteristic verification of the encapsulated superabsorbent core fails. If the half-maximum response time exceeds the standard while the response intensity ratio meets the standard, it is diagnosed as "slow response dynamics". In this case, the thickness of the smart film layer should be reduced or the porosity of the encapsulated superabsorbent core should be increased. If the response intensity ratio is not up to standard but the half-maximum response time is up to standard, it is diagnosed as "insufficient response thermodynamics", and the proportion of responsive functional groups in the smart film-forming polymer is increased. If both the half-maximum response time and the response intensity ratio fail to meet the standards, it is diagnosed as a "comprehensive failure". In this case, the proportion of responsive functional groups in the smart film-forming polymer is increased and the porosity of the encapsulated superabsorbent core is improved.

[0040] Specifically, two equal volumes of the encapsulated core sample were placed in phosphate-buffered saline (PBS, solution 1) at pH 7.4 (simulating normal tissue fluid) and Tris-HCl buffer at pH 8.0 (solution 2), respectively. The samples were incubated in a shaker at 37°C. Samples were periodically removed, blotted dry with filter paper, weighed, and the degree of swelling was calculated. The swelling kinetics were monitored over 3 hours, and the results are shown in Table 1. Table 1. Swelling kinetics of encapsulated superabsorbent cores in solutions at pH 7.4 and pH 8.0

[0041] As shown in the table above, in the pH 7.4 solution, the swelling degree stabilized at 3.3 after 90 minutes and no longer increased; in the pH 8.0 solution, the swelling degree stabilized at 9.2 after 120 minutes. At this point, the material is considered to have reached swelling equilibrium. Plotting the time-swelling degree curve yields the following: Maximum equilibrium swelling degree at pH 7.4 ; Maximum equilibrium swelling degree at pH 8.0 ; The half-maximum response time (t½) refers to the time required from contact with the stimulus solution until its swelling reaches 50% of the maximum equilibrium swelling in the solution.

[0042] By fitting a curve, the SR(t) data in Table X (typically in the initial rising phase, such as t=0 to 60 min) is nonlinearly fitted. The Boltzmann growth function or a single exponential growth model is commonly used for fitting. In this embodiment, a single exponential model is used:

[0043] Where SR(t) is the degree of swelling at time t. Let τ be the maximum equilibrium swelling degree at pH 8.0, and τ be the characteristic time constant. According to the table above, substituting SR(t) = 4.6, we get τ ≈ 21.6 minutes. Therefore, the half-maximum response time is: t 1 / 2 ≈21.6 × 0.693 ≈ 15 minutes The response intensity ratio R (the ratio of the maximum equilibrium swelling degree at pH 8.0 to pH 7.4) is 2.8. The preset pass threshold standard is: t½ ≤ 13 minutes, R ≥ 2.0. For this batch of samples, t½ = 15 minutes > 13 minutes (not meeting the standard), R = 2.8 ≥ 2.0 (meets the standard). According to the rules, the intelligent response characteristic verification of this batch of samples is deemed unsuccessful. It is judged as "slow response kinetics," requiring a reduction in the thickness of the intelligent membrane and an increase in its porosity. That is, in step S23, in the microfluidic device, the oil phase flow rate is increased to 3.0 mL / h, while the aqueous phase flow rate remains unchanged (650 μL / h). This significantly increases the two-phase flow rate ratio, generating smaller droplets in the microfluidic channel. Smaller droplets result in a thinner calcium alginate pre-coating layer formed in the curing bath. In step S24, a 2% (w / v) calcium chloride solution is used as the curing bath, allowing for sufficient crosslinking time. This reduces the crosslinking agent concentration in the subsequent genipin chemical crosslinking step from 0.5% (w / v) to 0.25% (w / v) and shortens the crosslinking time from 6 hours to 3 hours. This contributes to the formation of a final smart membrane structure with lower crosslinking density and greater porosity, accelerating mass transport. The smart response characteristics were retested; this time, t½ was 10 minutes, and R was 3.0, indicating successful verification.

[0044] Step S3: Dissolve chitosan and carboxymethyl chitosan in an alkaline solution and stir continuously until a homogeneous, clear or slightly opalescent viscous solution is formed, thus obtaining an alkaline polysaccharide mixture. Specifically, chitosan (degree of deacetylation ≥ 90%) and carboxymethyl chitosan (degree of substitution ≥ 80%) were weighed and mixed at a mass ratio of 2:1, and added to a 1% (w / v) sodium hydroxide aqueous solution to make the total polysaccharide concentration 3% (w / v). The mixture was continuously mechanically stirred (500 rpm) at room temperature for 6 hours until a homogeneous, slightly opalescent viscous solution was formed, thus obtaining an alkaline polysaccharide mixture.

[0045] Step S4: Obtain the alkaline polysaccharide mixture, add oxidized regenerated cellulose in portions while stirring, monitor the system viscosity in real time, and dynamically adjust the addition rate and stirring rate of oxidized regenerated cellulose based on the system viscosity value to keep the system viscosity within a preset range to ensure uniform dispersion. Specifically, the 300g alkaline polysaccharide mixture obtained in step S3 was placed in a stirred reactor equipped with an online viscosity probe (Brookfield DV3T), and the stirring speed was maintained at 300 rpm. A total of 6.0g of oxidized regenerated cellulose (ORC) powder was added in batches, with a target final ORC concentration of 2% (w / v). The preset viscosity control range was 2000-2500 mPa·s. The initial addition rate was relatively fast, for example, 0.5g / min. When the viscosity probe showed that the system viscosity dropped to 1800 mPa·s, the control system automatically increased the ORC addition rate, for example, by 15%; when the viscosity rose to 2800 mPa·s, the stirring speed was automatically increased to 400 rpm and the addition rate was reduced, for example, by 20%, so that the viscosity returned to the preset range. This dynamic adjustment was continued until all ORC was added and the system viscosity stabilized at approximately 2200 mPa·s.

[0046] Step S5: After all the oxidized regenerated cellulose has been added, the storage modulus and loss modulus are detected by a rheometer to determine the starting point of gelation. Based on the growth rate of the storage modulus, the gelation state is determined to obtain a carrier substrate gel solution with a preliminary three-dimensional network. The starting point for determining gelation is defined as the moment when the storage modulus (G') is first and continuously greater than the loss modulus (G''), and the ratio G' / G''>1 is established. This moment is recorded as the starting point for gelation.

[0047] The determination of the gelation state based on the growth rate of the energy storage modulus includes: If the growth rate is greater than the first preset threshold R1, it is determined to be rapid gelation, which is a "loose and porous gel state". If the growth rate of the energy storage modulus is greater than the second preset threshold R2 and less than or equal to the first preset threshold R1, it is determined to be "equilibrium gel state"; If the growth rate of the energy storage modulus is less than or equal to the second preset threshold R2, it is determined to be a "dense gel state".

[0048] If the state is "dense gel state", monitoring must continue until the energy storage modulus (G') reaches a preset final modulus absolute value G3 before shearing can be stopped or the next process can be started.

[0049] The preset thresholds R1 and R2, as well as the preset final modulus G_final, can be determined through preliminary experiments based on the mechanical performance requirements of the target gel product (such as the rigidity and elasticity required for the dressing). In a preferred embodiment of the present invention, R1 = 50 Pa / min, R2 = 10 Pa / min, and G3 = 200 Pa are set.

[0050] Specifically, the final mixture obtained in step S4 was transferred to the parallel plate fixture of a rheometer (such as TA Instruments DHR) for time-scan testing (strain 1%, angular frequency 1 rad / s, temperature 25°C). The storage modulus (G1) and loss modulus (G2) were monitored in real time, and the results are shown in Table 2.

[0051] Note: The moment when the storage modulus G1 first and continuously exceeds the loss modulus G2 is denoted as the starting point t of gelation. gel .

[0052] The calculated average growth rate is 25.4 Pa / min. The preset thresholds are R1=50 Pa / min and R2=10 Pa / min. The condition is determined to be a uniform gel state, and the carrier base gel solution is obtained.

[0053] Step S6: Obtain the carrier substrate gel solution. Based on the gelation state and the verification results of encapsulating the superabsorbent core, adaptively select the active ingredient loading strategy. By monitoring the dispersion uniformity index of the mixed system, determine whether the active factor has been completely encapsulated. Then, allow the network to stabilize at low temperature to obtain the carrier gel. In step S6, based on the gelation state and the verification results of the encapsulated superabsorbent core, an adaptive active ingredient loading strategy is selected, including: If it is a "loose and porous gel state", the encapsulated superabsorbent core is mixed in first, and then the epidermal growth factor solution is added at low temperature and slow speed to facilitate its diffusion into the pores. If the gel is in a "balanced gel state" or "dense gel state", a strategy is adopted to preload human epidermal growth factor onto part of the surface of the encapsulated superabsorbent core and then mix it in as a whole, in order to protect the activity of the factor and achieve targeted release.

[0054] Specifically, human epidermal growth factor is preloaded onto the surface of a portion of the encapsulated superabsorbent core, including: Step S61: Human epidermal growth factor is dissolved in a physiologically compatible buffer solution to obtain an active factor loading solution. Step S62: Immerse the encapsulated superabsorbent core in the active factor loading solution and incubate it under the condition of maintaining the biological activity of human epidermal growth factor, so that the human epidermal growth factor is adsorbed onto the surface of the encapsulated superabsorbent core through non-covalent interaction. Step S63: After incubation, the encapsulated superabsorbent core that has completed surface adsorption is separated from the remaining liquid to obtain a functionalized absorbent core with human epidermal growth factor preloaded on the surface.

[0055] Specifically, a PBS buffer (pH 7.4) containing human epidermal growth factor (rhEGF) at a concentration of 100 µg / mL was prepared. Approximately 30% of the encapsulation cores prepared in step S2 were immersed in the above rhEGF solution and gently incubated with shaking at 4°C for 2 hours. After incubation, the microspheres were separated by centrifugation and gently washed once with a small amount of PBS to obtain functionalized absorber cores pre-loaded with rhEGF. The remaining 70% of the unloaded encapsulation cores, along with all the functionalized absorber cores, were added to the carrier base gel solution obtained in step S5 and mixed at low speed (100 rpm) for 10 minutes. Simultaneously, the turbidity change of the mixture was monitored using an online turbidimeter. When the turbidity change rate was below 0.5% / min for 5 consecutive minutes, the active factor encapsulation was considered complete. The entire system was then transferred to a 4°C refrigerator and allowed to stand for 12 hours to allow the three-dimensional network to fully stabilize, resulting in the carrier gel.

[0056] Step S7: Obtain the carrier gel, add Bletilla striata polysaccharide solution, and fuse at a constant temperature; monitor the change in system viscosity, and when the viscosity reaches its peak and enters the plateau period, it is determined that the fusion of Bletilla striata polysaccharide network is complete, and a composite gel is obtained; Step S7 includes: Step S71: Under constant temperature and continuous stirring, add the Bletilla striata polysaccharide solution to the carrier gel, and simultaneously start continuous monitoring of the viscosity of the system; Step S72: Based on the viscosity monitoring data, plot the viscosity-time curve and calculate the instantaneous rate of change of viscosity in real time; Step S73: When the instantaneous rate of change of viscosity changes from a positive value to a negative value for the first time, continue monitoring. When the viscosity data enters and remains within a stable fluctuation range, it is determined that the fusion of Bletilla striata polysaccharide network is complete.

[0057] The stable fluctuation range refers to the relative deviation of at least three consecutive viscosity measurements not exceeding a preset threshold, preferably, the preset threshold δ=2%.

[0058] Specifically, the carrier gel was brought to room temperature and placed in a thermostatic stirrer (30°C) and stirred at a slow speed (150 rpm).

[0059] To prepare a 2% (w / v) aqueous solution of Bletilla striata polysaccharide: Accurately weigh 2.00 g of Bletilla striata polysaccharide powder. Measure approximately 80 mL of water for injection, maintained at 50-60°C, and place it in a container equipped with a stirrer. While stirring at 300-500 rpm, slowly and evenly sprinkle the Bletilla striata polysaccharide powder into the warm water, avoiding clumping. Continue stirring until the powder is completely dispersed. Stop heating and allow the solution to cool to room temperature (approximately 25°C). Add water for injection until the total mass of the solution is 100.00 g.

[0060] Take 20.00 g of the prepared 2.0% Bletilla striata polysaccharide aqueous solution (containing 0.40 g of Bletilla striata polysaccharide) and add it to 200.00 g of carrier gel. Simultaneously monitor the viscosity of the system continuously using a viscometer. The results are shown in Table 3. Plot the viscosity-time curve based on the monitoring data and calculate the instantaneous rate of change.

[0061] Table 3. Viscosity monitoring results during the fusion process of Bletilla striata polysaccharide network.

[0062] Table 3 shows that the viscosity continues to rise with a positive rate of change. After about 15 minutes, the rate of change turns negative for the first time, indicating that the viscosity has reached its peak. Subsequently, the viscosity fluctuates within a small range.

[0063] Take the viscosity values ​​at the last three points (t=18.5, 19.0, 19.5 min): 12458, 12455, 12452 mPa·s, and calculate the average viscosity η. avg =12455 mPa·s, calculate the relative deviation: For 12458: |12458-12455| / 12455×100%=0.024%; For 12455: 0.00%; For 12452: 0.024% The maximum relative deviation was 0.024%, which is much smaller than the preset threshold δ=2%.

[0064] At this point, the fusion of the Bletilla striata polysaccharide network is considered complete. Stirring is stopped, and the system is allowed to stand at 4°C for 12 hours to solidify, resulting in a structurally stable composite gel.

[0065] Step S8: Obtain the composite gel, add Bletilla striata plant essential oil, and emulsify and disperse it; after determining by microscopic observation that the essential oil has reached the preset micro-dispersion standard, stop emulsification, and let it stand at low temperature to solidify, thereby obtaining the Bletilla striata compound gel.

[0066] Step S8 includes: Step S81: Slowly add Bletilla striata plant essential oil to the composite gel and apply a first horizontal shear force for initial dispersion to obtain a first dispersion. Step S82: Obtain the first dispersion, apply a second horizontal shear force for fine dispersion, and obtain the second dispersion; Step S83: Obtain the particle size distribution data of essential oil droplets in the second dispersion. When the particle size distribution data simultaneously meets the preset upper limit of particle size and the distribution uniformity standard, and remains stable, it is determined that the emulsification and dispersion is complete.

[0067] Specifically, based on previous activity screening and formulation stability studies, the effective and safe addition ratio of Bletilla striata essential oil (Bletilla striata volatile oil, the main components of which are ≥15% blemishene, ≥8% eucalyptol, ≥5% eugenol, and the remainder being monoterpenes and sesquiterpenes) was determined to be 0.5%–2% (w / w). In this example, it was added at 1% of the total mass of the composite gel. The specific operation was as follows: 100g of composite gel was weighed, and 1.0g of Bletilla striata essential oil was slowly added dropwise to the composite gel obtained in step S7. At the same time, a moderate shear force (using a high-speed disperser, 5000rpm) was applied for preliminary emulsification for 3 minutes to obtain the first dispersion.

[0068] The first dispersion was transferred to a high-pressure homogenizer and homogenized three times at a pressure of 50 MPa to achieve fine dispersion, thus obtaining the second dispersion.

[0069] Take a small amount of the second dispersion and determine the particle size distribution of the essential oil droplets using an optical microscope combined with image analysis software. The endpoint of the emulsification dispersion is determined by the particle size distribution of the essential oil droplets in the dispersion, and must simultaneously meet the following two preset criteria.

[0070] Upper limit standard for droplet size: The average droplet size (D50) is <10μm, and 90% of the droplet sizes (D90) are <15μm.

[0071] Uniformity standard: The span of the particle size distribution should be less than 2.0. The formula for calculating the span is:

[0072] Wherein, D50 is the median particle size, representing that 50% of the droplets in the sample are smaller than this particle size; D90 is the characteristic particle size, representing that 90% of the droplets in the sample are smaller than this particle size; D10 represents that 10% of the droplets in the sample are smaller than this particle size; the smaller the Span value, the more concentrated and uniform the particle size distribution.

[0073] The test results are shown in Table 4: Table 4. Droplet size distribution of Bletilla striata plant essential oil emulsion.

[0074] The preset standards are: average particle size <10 micrometers, D90 <15 micrometers, and span <2.0. The average particle size of the droplets in this batch of samples was measured to be 3.5 micrometers, the D90 (90% of droplets are smaller than this value) was 7.8 micrometers, and the distribution was uniform, with a span of 1.8 < 2.0. This batch of samples meets the standards, and the emulsification and dispersion are deemed complete. The final product was dispensed and allowed to stand at 4°C for 24 hours to solidify, thus obtaining the Bletilla striata compound gel. Example 2:

[0075] The difference between this embodiment and Embodiment 1 is that: The response target of the smart membrane in step S2. A peptide (sequence: PVGLIG) sensitive to matrix metalloproteinase-9 (MMP-9, highly expressed in chronic wounds) is selected as the response element and grafted onto the amphiphilic polymer of polyethylene glycol-polylactic-glycolic acid copolymer (PEG-PLGA) to form a smart film-forming material.

[0076] In step S23, coating is performed using a solvent evaporation method. During verification in step S25, the first solution is a buffer solution without MMP-9, and the second solution is a buffer solution containing active MMP-9 (100 ng / mL). The verification criterion remains the difference in swelling behavior. The remaining steps are similar to those in Example 1, ultimately yielding a compound gel with a smart response to MMP-9. Example 3:

[0077] The difference between this embodiment and Embodiment 1 is that, in step S5, the measured growth rate of the storage modulus is approximately 60 Pa / min (greater than R1), which is determined to be a "loose porous gel state". In step S6, the encapsulated superabsorbent core is first mixed in, and then the epidermal growth factor solution is added dropwise at low temperature and at a slow rate to facilitate its diffusion into the pores. The rest is the same as in Embodiment 1.

[0078] Comparative Example 1: Comparative samples were prepared according to the formulation and process of Example 1 in CN109776819A.

[0079] Comparative Example 2: Comparative samples were prepared according to the formulation and process of Example 1 in CN120168702A.

[0080] Comparative Example 3: Comparative samples were prepared according to the formulation and process of Example 1 in CN120324333A.

[0081] The gels prepared in Examples 1-3 and Comparative Examples 1-3 of this invention were subjected to performance tests, and the experimental results are shown in Table 5: Table 5. Overall performance comparison between the embodiments of the present invention and the comparative examples.

[0082] As shown in Table 5, the compound gels prepared in Examples 1-3 of this invention are significantly superior to comparative examples 1-3, which represent the prior art, in terms of intelligent responsiveness, process controllability and product uniformity, efficient loading and protection of active ingredients, and comprehensive bioactivity. This fully verifies that this invention, through a systematic design of "intelligent core construction + adaptive process control + multi-network fusion," successfully overcomes the key problems mentioned in the background art, such as passive function, crude process, insufficient activity protection, and low integration, providing a high-performance comprehensive solution for the clinical management of complex chronic wounds.

[0083] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a gel that promotes wound healing, characterized in that, include: Step S1: Prepare superabsorbent polymer microspheres as absorption cores; The polymer is selected from one or more of sodium polyacrylate, starch-grafted acrylate, and sodium carboxymethyl cellulose. Step S2: Perform surface functionalization treatment on the superabsorbent polymer microspheres, coat them with a smart film layer that is sensitive to biomarkers of the wound microenvironment to form an encapsulated superabsorbent core, and verify the smart response characteristics of the encapsulated superabsorbent core. Step S3: Dissolve chitosan and carboxymethyl chitosan in an alkaline solution and stir continuously until a homogeneous, clear or slightly opalescent viscous solution is formed, thus obtaining an alkaline polysaccharide mixture. Step S4: Obtain the alkaline polysaccharide mixture, add oxidized regenerated cellulose in portions while stirring, monitor the system viscosity in real time, and dynamically adjust the addition rate and stirring rate of oxidized regenerated cellulose based on the system viscosity value to keep the system viscosity within a preset range to ensure uniform dispersion. Step S5: After all the oxidized regenerated cellulose has been added, the storage modulus and loss modulus are detected by rheometer to determine the starting point of gelation, and the gelation state is determined based on the growth rate of the storage modulus to obtain a carrier substrate gel solution with a preliminary three-dimensional network. Step S6: Obtain the carrier substrate gel solution, and adaptively select the active ingredient loading strategy based on the gelation state and the verification results of encapsulating the superabsorbent core. By monitoring the dispersion uniformity index of the mixed system, it is determined whether the active factor has been completely encapsulated. After completion, the network is stabilized by low-temperature static incubation to obtain the carrier gel. Step S7: Obtain the carrier gel, add Bletilla striata polysaccharide solution, and fuse at a constant temperature; monitor the change in system viscosity, and when the viscosity reaches its peak and enters the plateau period, it is determined that the fusion of Bletilla striata polysaccharide network is complete, and a composite gel is obtained; Step S8: Obtain the composite gel, add Bletilla striata plant essential oil, emulsify and disperse it. After determining by microscopic observation that the essential oil has reached the preset micro-dispersion standard, stop emulsification, let it stand at low temperature to solidify, and obtain the Bletilla striata compound gel.

2. The method for preparing the wound-healing gel according to claim 1, characterized in that, Step S2 includes: Step S21: Disperse the superabsorbent polymer microspheres in a solvent, remove surface impurities by washing, and activate the surface to enhance surface energy or introduce active functional groups to obtain activated superabsorbent polymer microspheres. Step S22: Determine the concentration of the smart film-forming polymer with specific responsiveness based on the pH value of the target wound; Step S23: Mix the activated polymer microspheres with the smart film-forming polymer solution to form a uniform pre-coating layer on the surface of the microspheres; Step S24: The pre-coating layer is cured to form a structurally stable smart film layer, thereby obtaining the encapsulated superabsorbent core; Step S25: Obtain the encapsulated superabsorbent core, place it in a solution simulating the presence of the target biomarker, and verify the intelligent response characteristics.

3. The method for preparing the wound-healing gel according to claim 2, characterized in that, Step S25 includes: Step S251: The encapsulated superabsorbent core sample is placed in a first solution simulating a normal healing environment and a second solution simulating the abnormal presence of the target biomarker, respectively. S252: Real-time monitoring and recording of swelling kinetics data for two groups of samples within a preset time period; S253: Based on monitoring data, calculate the half-maximum response time and response intensity ratio of the encapsulated superabsorbent core in the second solution; The half-maximum response time is the time required from contact with the second solution until its swelling degree reaches 50% of the maximum equilibrium swelling degree in the solution; The response intensity ratio R is the ratio of the maximum equilibrium swelling degree in the second solution to the maximum equilibrium swelling degree in the first solution; S254: Compare the calculated half-maximum response time and R value with a preset qualified threshold to determine whether the smart response characteristics of the encapsulated superabsorbent core have been verified.

4. The method for preparing the wound-healing gel according to claim 3, characterized in that, In step S254, if the smart response characteristic verification of the encapsulated superabsorbent core fails, an adjustment instruction is generated based on the exceedance of the half-maximum response time and response intensity ratio. If the half-maximum response time exceeds the standard while the response intensity ratio meets the standard, it is diagnosed as "slow response dynamics". In this case, the thickness of the smart film layer should be reduced or the porosity of the encapsulated superabsorbent core should be increased. If the response intensity ratio is not up to standard but the half-maximum response time is up to standard, it is diagnosed as "insufficient response thermodynamics", and the proportion of responsive functional groups in the smart film-forming polymer is increased. If both the half-maximum response time and the response intensity ratio fail to meet the standards, it is diagnosed as a "comprehensive failure". In this case, the proportion of responsive functional groups in the smart film-forming polymer is increased and the porosity of the encapsulated superabsorbent core is improved.

5. The method for preparing the wound-healing gel according to claim 1, characterized in that, In step S6, based on the gelation state and the verification results of the encapsulated superabsorbent core, an adaptive active ingredient loading strategy is selected, including: The gelation state is determined based on the comparison between the growth rate of the energy storage modulus and the first preset threshold and the second preset threshold. If the growth rate of the energy storage modulus is greater than the second preset threshold and less than or equal to the first preset threshold, it is determined to be "equilibrium gel state"; If the growth rate of the energy storage modulus is less than or equal to the second preset threshold, it is determined to be "dense gel state"; For "equilibrium gel state" or "dense gel state", a strategy is adopted to preload human epidermal growth factor onto part of the surface of the encapsulated superabsorbent core and then mix it in as a whole, in order to protect the activity of the factor and achieve targeted release.

6. The method for preparing the wound-healing gel according to claim 5, characterized in that, Human epidermal growth factor was preloaded onto the surface of a partially encapsulated superabsorbent core, including: Step S61: Human epidermal growth factor is dissolved in a physiologically compatible buffer solution to obtain an active factor loading solution. Step S62: Immerse the encapsulated superabsorbent core in the active factor loading solution and incubate it under the condition of maintaining the biological activity of human epidermal growth factor, so that the human epidermal growth factor is adsorbed onto the surface of the encapsulated superabsorbent core through non-covalent interaction to obtain the mixed system. Step S63: After incubation, the encapsulated superabsorbent core that has completed surface adsorption is separated from the remaining liquid to obtain a functionalized absorbent core with human epidermal growth factor preloaded on the surface.

7. The method for preparing the wound-healing gel according to claim 1, characterized in that, The dispersion uniformity index of the mixed system includes one or more of the following: turbidity, transmittance, or coefficient of variation of zeta potential. Determining whether the active ingredient has been successfully encapsulated includes: If the rate of change of turbidity or transmittance drops below a preset threshold and remains stable, or the coefficient of variation of the zeta potential drops below a preset threshold and remains stable, then the encapsulation of the active factor is considered complete.

8. The method for preparing the wound-healing gel according to claim 1, characterized in that, Step S7 includes: Step S71: Under constant temperature and continuous stirring, add the Bletilla striata polysaccharide solution to the carrier gel, and simultaneously start continuous monitoring of the viscosity of the system; Step S72: Based on the viscosity monitoring data, plot the viscosity-time curve and calculate the instantaneous rate of change of viscosity in real time; Step S73: When the instantaneous rate of change of viscosity first changes from a positive value to a negative value, continue monitoring. When the viscosity data enters and remains within a stable fluctuation range, it is determined that the fusion of Bletilla striata polysaccharide network is complete. The stable fluctuation range refers to the relative deviation of at least three consecutive viscosity measurements not exceeding a preset threshold.

9. The method for preparing the wound-healing gel according to claim 1, characterized in that, Step S8 includes: Step S81: Slowly add Bletilla striata plant essential oil to the composite gel and apply a first horizontal shear force for initial dispersion to obtain a first dispersion. Step S82: Obtain the first dispersion, apply a second horizontal shear force for fine dispersion, and obtain the second dispersion; Step S83: Obtain the particle size distribution data of essential oil droplets in the second dispersion. When the particle size distribution data simultaneously meets the preset upper limit of particle size and the distribution uniformity standard, and remains stable, it is determined that the emulsification and dispersion is complete.

10. A gel that promotes wound healing, characterized in that, The gel, prepared by any one of claims 1-9, is used in dressings for managing highly exudative or easily infected chronic wounds.

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