Programmable hydrogel wound dressing with rotational contractile force and applications thereof

Abstract

The application provides a programmable hydrogel wound dressing with rotary contractive force and application thereof, and belongs to the technical field of biomedical materials, and comprises: a double-network hydrogel main body composed of a first network and a second network; the first network is a chemically cross-linked methacrylated hyaluronic acid network, and the cross-linked network structure is formed through photo polymerization; the second network is a physically cross-linked polyvinyl alcohol network, and the instantaneous cross-linking points are formed through hydrogen bonds and crystal regions, and the hydrogel is endowed with shape memory performance; the surface is modified with N-hydroxysuccinimide ester functional groups, which can form covalent bonds with the amino groups of tissue proteins on a wound surface; the double-network hydrogel main body is dried and shaped into a preset shape after being pre-stretched or pre-twisted, restores the initial shape after absorbing moisture, and outputs a rotary contractive mechanical force. The application realizes rapid wound healing and scar-free regeneration by dynamically regulating the mechanical force at the wound edge and enhancing tissue adhesion, and further realizes the application in regulating the wound microenvironment to promote scar-free healing.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a programmable hydrogel wound dressing with rotary contractile force and application thereof. BACKGROUND

[0002] Mechanical tension is a key factor in regulating fibroblast behavior, collagen deposition and scar formation - moderate tension can promote cell migration and angiogenesis, while high strength and persistent stress can lead to sustained activity of myofibroblasts, inducing abnormal scars.

[0003] Currently, the tension reduction means used in clinical practice (such as silicone sheets, compression garments, tension suture devices, etc.) have significant limitations: first, they lack dynamic regulation ability and can only provide static or passive tension reduction, which cannot meet the needs of different healing stages of the wound surface; second, the force field direction is single, mostly linear or vertical force, ignoring the complex multidirectional stress distribution of the wound margin, which is easy to cause stress concentration; third, the wet environment adaptability is poor, most materials are easy to slip off in a wet wound surface, and it is difficult to have a lasting effect; fourth, the shape memory function and mechanical regulation strategy have not been integrated, and the spatial programmable output of force cannot be achieved. In addition, although some studies have shown that intervention in the mechanical transduction signaling pathways such as YAP or TGF-β can reduce scars, these pathways are essential for cell proliferation and matrix synthesis in the early stages of healing, and single inhibition cannot balance tissue regeneration and scar inhibition. Therefore, there is an urgent need for a hydrogel wound dressing with programmable mechanical output ability, good tissue adhesion performance, and the ability to dynamically adjust the mechanical microenvironment of the wound margin, in order to achieve scar-free tissue regeneration and repair. SUMMARY

[0004] In order to overcome the shortcomings of the prior art, the purpose of the present application is to provide a programmable hydrogel wound dressing with rotary contractile force and application thereof.

[0005] To achieve the above-mentioned purpose, the present application provides the following solutions:

[0006] One of the purposes of the present application is to provide a programmable hydrogel wound dressing with rotary contractile force, comprising:

[0007] The double-network hydrogel body is composed of a first network and a second network; the first network is a chemically cross-linked methacrylated hyaluronic acid network, which forms an interpenetrating network structure through photopolymerization; the second network is a physically cross-linked polyvinyl alcohol network, which forms transient cross-linking points with crystal regions through hydrogen bonds, giving the hydrogel shape memory properties;

[0008] The double-network hydrogel body is modified with N-hydroxysuccinimide ester functional groups on its surface, which can form covalent bonds with the amino groups of the proteins in the wound tissue;

[0009] The double-network hydrogel body is dried and shaped into a preset shape after being pre-stretched or pre-twisted, and restores the original shape and outputs the mechanical force of rotational contraction after absorbing moisture.

[0010] The second object of the present application is to provide a preparation method of the programmable hydrogel wound dressing with rotational contraction force, comprising the following steps:

[0011] S1, mixing polyvinyl alcohol solution and methacrylated hyaluronic acid solution, adding photoinitiator and acrylic acid-NHS, and completing photopolymerization by ultraviolet irradiation to obtain a wet double-network hydrogel;

[0012] S2, the wet double-network hydrogel is pre-stretched or pre-twisted, and then dried at 50-60 DEG C for 40-50 hours to form a shape memory structure, thereby obtaining the programmable hydrogel wound dressing.

[0013] The third object of the present application is to provide a use method of the programmable hydrogel wound dressing with rotational contraction force, which is attached to the surface of a moist wound, and the programmable hydrogel wound dressing starts shape recovery after absorbing wound exudate and outputs directional mechanical stimulation to the wound edge.

[0014] The fourth object of the present application is to provide an application of the programmable hydrogel wound dressing with rotational contraction force in regulating the microenvironment of the wound surface to promote scarless healing.

[0015] According to the specific embodiments provided by the present application, the following technical effects are disclosed:

[0016] (1) The programmable hydrogel wound dressing provided by the present application has the ability to precisely regulate the mechanical microenvironment of the wound edge, and through the design of the shape memory structure, it can output tension or rotational stress with controllable direction and adjustable strength at different stages of wound healing, realizing the spatiotemporal redistribution of local stress on the wound edge. Animal experiments show that it can promote the activation of YAP and TGF-beta signaling pathways in the early stage to accelerate cell migration and angiogenesis, and inhibit related pathways in the late stage to reduce excessive collagen deposition, thereby balancing tissue regeneration and scar inhibition.

[0017] (2) The programmable hydrogel wound dressing provided by the present application can significantly improve wound closure efficiency and tissue reconstruction quality, while reducing scar formation. In a diabetic mouse model, the wound closure rate of the treatment group using the medium rotational force patch was more than 80% on the 16th day, which was much higher than that of the control group; in a rabbit ear scar model, the scar area was significantly smaller than that of the control group after 8 weeks of treatment, and the collagen fibers were arranged more closely to normal skin, with both aesthetic and functional properties.

[0018] (3) The programmable hydrogel wound dressing provided by the application also has excellent practical performance, the surface NHS group modification enables the programmable hydrogel wound dressing to have high-strength adhesion on a wet tissue surface, the tensile adhesion strength reaches 120 kPa, the interfacial fracture toughness is higher than 450 J / m 2 , and can stably act on a complex wound surface. The mechanical output response is fast, and effective shape recovery and force output can be completed within 20 seconds without an external energy source, which is convenient for clinical operation. Meanwhile, the material is biodegradable, low-cost, and easy to mass-produce, thereby reducing the need for subsequent treatments such as postoperative scar repair, skin grafting or laser treatment, and further reducing the medical cost. The programmable hydrogel wound dressing is especially suitable for various clinical scenarios such as diabetic foot, burn and plastic surgery. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 FIG. 1 is a scanning electron microscope (SEM) image of the programmable hydrogel wound dressing with rotary contraction force according to the application;

[0020] Figure 2 FIG. 2 is a schematic diagram of the shape memory mechanism of the programmable hydrogel wound dressing with rotary contraction force according to the application;

[0021] Figure 3 FIG. 3 is a preset shape and mechanical output mode diagram of the programmable hydrogel wound dressing with rotary contraction force according to the application; wherein, Figure 3 (a) in FIG. 3 is a schematic diagram of the preset shape and the corresponding mechanical output mode, Figure 3 (b) in FIG. 3 is a schematic diagram of stress concentration distribution on the wound edge without the patch, Figure 3 (c) in FIG. 3 is a schematic diagram of stress dispersion distribution on the wound edge after the rotary contraction patch is activated, Figure 3 (d) in FIG. 3 is a comparison diagram of wound area changes of different treatment groups at 0 minutes and 20 minutes in a pig skin round wound model;

[0022] Figure 4 FIG. 4 is a flowchart of the preparation method of the programmable hydrogel wound dressing with rotary contraction force according to the application;

[0023] Figure 5 FIG. 5 is a use state and mechanism diagram of the programmable hydrogel wound dressing with rotary contraction force according to the application; wherein, Figure 5 (a) in FIG. 5 is a schematic diagram of the three stages of wound healing (inflammation stage, proliferation stage and remodeling stage) and the dynamic change characteristics of the tissue, Figure 5 (b) in FIG. 5 is a schematic diagram of the mechanism of preventing scar formation by programmable external stress, Figure 5 (c) in FIG. 5 is a schematic diagram of the application model of the hydrogel patch attached to the skin wound;

[0024] Figure 6 FIG. 6 is a performance data diagram of the programmable hydrogel wound dressing with rotary contraction force according to the application; wherein,Figure 6 (a) shows the infrared spectra of unmodified and modified NHS ester hydrogels. Figure 6 (b) shows the water absorption and swelling curves of unmodified and modified NHS ester hydrogels. Figure 6 (c) in the figure is a comparison of the storage modulus (G') and loss modulus (G'') of unmodified and modified NHS ester hydrogels at different frequencies. Figure 6 (d) in the figure represents the tensile stress-strain curves of unmodified and modified NHS ester hydrogels. Figure 6 (e) shows a schematic diagram of the overlap shear experiment and shear stress-displacement curves of unmodified and modified NHS ester hydrogels. Figure 6 (f) shows a schematic diagram of the 180° shear experiment and shear force-displacement curves of unmodified and modified NHS ester hydrogels. Figure 6 (g) in the figure is a schematic diagram of the tensile test and tensile stress-displacement curves of unmodified and modified NHS ester hydrogels. Figure 6 (h) in the figure is a comparison of the interfacial shear force and tensile force test results of unmodified and modified NHS ester hydrogels. Figure 6 (i) in the figure shows the test results of the overlap shear stress of the hydrogel on different tissues. Figure 6 Figure (j) shows the test results of the adhesion force of the hydrogel to the 180° shear interface of different tissues. Figure 6 (k) in the figure is a comparison of the wound-closing force of the modified NHS ester hydrogel and the commercial material;

[0025] Figure 7 This is a performance graph evaluating the wound healing effect of the present invention in a diabetic mouse model; wherein, Figure 7 (a) shows the wound appearance photographs on days 0, 4, 8, and 16 in a 5mm full-thickness skin defect model on the back of diabetic mice in different treatment groups. Figure 7 (b) in the figure shows the quantitative curves of wound area changes over time for different treatment groups. Figure 7 (c) shows the H&E staining images of wound tissues from different treatment groups on days 8 and 16. Figure 7 (d) in the figure is a quantitative analysis of the degree of wound reepithelialization in different treatment groups;

[0026] Figure 8 This is a schematic diagram illustrating the wound healing mechanism controlled by the rotational shrinkage hydrogel patch according to the present invention; wherein, Figure 8 (a) in the figure shows the quantitative analysis of IL-6 expression levels in different treatment groups. Figure 8 (b) in the figure shows the quantitative analysis of TNF-α expression levels in different treatment groups. Figure 8 (c) in the figure is a quantitative analysis diagram of CD31 positive blood vessel density in different treatment groups;

[0027] Figure 9Figure 1 is a schematic diagram of the mechanism of wound healing under the regulation of the rotating contractive hydrogel patch according to the present application; wherein, Figure 9 Figure 1(a) is a quantitative analysis diagram of the expression of a-SMA in different treatment groups, Figure 9 Figure 1(b) is a quantitative analysis diagram of the expression of TGF-β in different treatment groups, Figure 8 Figure 1(c) is a quantitative analysis diagram of the expression of YAP in different treatment groups;

[0028] Figure 10 Figure 2 is a long-term evaluation diagram of scar remodeling and tissue regeneration in a hypertrophic scar model of rabbit ears according to the present application; wherein, Figure 10 Figure 2(a) is a diagram of the appearance of wounds in different treatment groups at weeks 0, 2, 4, 6 and 8 in a hypertrophic scar model of rabbit ears, Figure 10 Figure 2(b) is a diagram of H&E staining of wound tissues in different treatment groups at weeks 4 and 8, Figure 10 Figure 2(c) is a diagram of Masson's trichrome staining of wound tissues in different treatment groups at weeks 4 and 8;

[0029] Figure 11 Figure 3 is a long-term evaluation diagram of scar remodeling and tissue regeneration in a hypertrophic scar model of rabbit ears according to the present application; wherein, Figure 11 Figure 3(a) is a diagram of Sirius Red staining of wound tissues in different treatment groups under polarized light at weeks 4 and 8, Figure 11 Figure 3(b) is a quantitative analysis diagram of the CD31 signal intensity in different treatment groups, Figure 11 Figure 3(c) is a quantitative analysis diagram of the a-SMA signal intensity in different treatment groups;

[0030] Figure 12 Figure 4 is a schematic diagram of the molecular mechanism revealed by transcriptome analysis that the hydrogel patch promotes healing and reduces scars through mechanical regulation according to the present application; wherein, Figure 12 Figure 4(a) is a whole gene expression circular heat map of wound tissues in different treatment groups at week 4, Figure 12 Figure 4(b) is a volcano plot of differential genes in the Rt-MC group and the RaC group;

[0031] Figure 13 Figure 5 is a GO enrichment analysis diagram of differential genes;

[0032] Figure 14 Figure 6 is a KEGG pathway analysis diagram of differential genes;

[0033] Figure 15 Figure 7 is a schematic diagram of the molecular mechanism revealed by transcriptome analysis that the hydrogel patch promotes healing and reduces scars through mechanical regulation according to the present application; wherein, Figure 15 Figure 7(a) is an immunofluorescence image of TGF-β and YAP in wound tissues in different treatment groups at weeks 4 and 8, Figure 15(b) in the figure is a quantitative analysis of the relative expression levels of TGF-β protein in different treatment groups. Figure 15 (c) in the figure is a quantitative analysis of the relative expression levels of YAP protein in different treatment groups;

[0034] Among them, in the bar chart corresponding to the above-mentioned attached figures, " "" is a marker for statistically significant differences, specifically defined as follows:

[0035] Different numbers of " Different "P-values" (probability values) indicate whether the difference between two groups of data (such as the experimental group and the control group, or different experimental groups) is statistically significant.

[0036] “ ": This means P < 0.05, which means the difference between the two groups is "statistically significant" (probability of occurrence < 5%).

[0037] “ ": This means P < 0.01, which means the difference between the two groups is "highly statistically significant" (probability of occurrence < 1%).

[0038] “ “”: This means P < 0.001, which means the difference between the two groups is “highly statistically significant” (probability of occurrence < 0.1%).

[0039] “ ": represents P<0.0001, meaning the difference between the two groups is "highly statistically significant" (probability of occurrence <0.01%).

[0040] Referring to the example, in Figure 1 middle" Its specific function is:

[0041] This is used to assess the statistical reliability of differences in TGF-β and YAP protein expression levels between the Rt-MC (medium-tension rotational shrinkage patch) group, RaC (simple radial shrinkage patch) group, Rt-HC (high-tension rotational shrinkage patch) group, and TEG (commercial dressing control group), or between different experimental groups. For example, it is used to assess the statistical reliability of differences in TGF-β and YAP protein expression levels between the Rt-MC group and the TEG group. "This indicates that the difference in protein expression levels between the two is extremely significant, the results are reliable, and the influence of random factors has been excluded." Detailed Implementation

[0042] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. Figure 2 As shown, the present invention provides a programmable hydrogel wound dressing with rotational contraction force, comprising:

[0043] A double-network hydrogel body, which is composed of a first network and a second network; wherein the first network is a chemically cross-linked hyaluronic acid methacrylate (HAMA) network, which forms a cross-linked network structure by photo-polymerization, specifically: wherein the concentration of the hyaluronic acid methacrylate is 3-5 vol%, and the photo-polymerization occurs by adding a photo-initiator (LAP) in an amount of 0.05-0.2 wt% under 365 nm ultraviolet light irradiation for 10-20 s, thereby forming a stable three-dimensional cross-linked network structure;

[0044] The second network is a physically cross-linked polyvinyl alcohol (PVA) network, and the concentration of the polyvinyl alcohol is 8-12 wt%, which forms reversible transient cross-linking points with crystal regions through hydrogen bonds, thereby giving the hydrogel shape memory performance, and the reversible destruction and reconstruction of the crystal region is the main principle for shape recovery, as shown in Figure 6 The initial state, the stretched and dried state, and the hydrated state are shown, and it should be noted that hydration refers to the process of the hydrogel absorbing water to restore the wet state, which is consistent with the meaning of "rehydration". In the initial state, the long chains of polyvinyl alcohol (PVA) in the hydrogel form a large number of hydrogen bonds and crystal regions (i.e., transient cross-linking points TCPs), which cooperates with the chemically cross-linked network formed by hyaluronic acid methacrylate (HAMA); at this time, the hydrogel is in a fully hydrated state, and the hydrogen bond and crystal region structure of the PVA chain segment is stable. When the hydrogel patch is pre-stretched and dried, the loss of water causes the crystal region (TCPs) of the PVA chain segment to be destroyed, and the hydrogen bond to be broken, thereby locking the stress and forming a dehydrated preset shape. When the dried hydrogel patch absorbs water (such as wound exudate) and hydrates (i.e., rehydrates), the PVA chain segment re-forms hydrogen bonds and reconstructs the crystal region (TCPs), releases the stored elastic energy, drives the hydrogel to recover to the initial fully hydrated state, and outputs the mechanical force of rotational contraction, thereby realizing the shape memory driving behavior.

[0045] In addition, the surface of the double-network hydrogel body is modified with an N-hydroxysuccinimide ester functional group, specifically: by introducing 1-3 wt% of acrylic acid-NHS (AAc-NHS) comonomer during the preparation of the hydrogel, the surface of the hydrogel is modified with an N-hydroxysuccinimide (NHS) ester functional group, which can rapidly form a covalent bond with the amino group of the protein of the wound tissue, thereby ensuring high-strength adhesion in a wet environment. As shown in Figure 3 As shown in (a) of FIG. 8, the infrared spectrum confirms the existence of the characteristic absorption peak of the NHS ester group by comparing the relevant characteristic peaks, thereby proving that the acrylic acid-NHS (AAc-NHS) comonomer successfully participates in the reaction during the preparation of the hydrogel, and the surface of the hydrogel is modified with the NHS ester functional group. The existence of this functional group is the key basis for the hydrogel to form a stable covalent bond with the amino group of the protein of the wound tissue, and to realize high-strength tissue adhesion performance in a wet environment, thereby providing an important guarantee for the stable effect of the hydrogel patch on the wound.

[0046] The double-network hydrogel body is dried and shaped into a preset shape after being pre-stretched or pre-twisted, and restores the initial shape and outputs mechanical force after absorbing moisture. The preset shape includes one or more of a spiral shape, a radial shape, and a strip shape, and the corresponding output mechanical force mode includes one or more of radial contraction, rotational contraction, and tension release. Figure 3 As shown in (a) of FIG. 1, the spiral shape, the radial shape, and the strip shape correspond to the three mechanical modes of rotational contraction, radial contraction, and tension release, respectively. The spiral-shaped patch generates a rotational torque after rehydration through a pre-twist angle (Δα = 35°~45°); the radial-shaped patch drives centripetal contraction through a high pre-stretch ratio (Δλ = 40%); and the strip-shaped patch releases uniform longitudinal tension. This programmable design solves the problem of single mechanical direction of traditional dressings and can directly match the biomechanical requirements of linear, circular, or irregular wounds.

[0047] According to the above, the stress field of the wound edge is reconstructed by mechanical output, and the scar is inhibited, as shown in (b) of FIG. 1, where the right side is a stress scale bar, specifically a single-dimensional color-value mapping bar, with a value range of 0-1 (dimensionless, representing relative stress intensity), red corresponding to a high value (1), and blue corresponding to a low value (0), for quantifying the strength difference of the stress distribution of the wound edge. Referring to (b) of FIG. 1, when there is no patch, the stress distribution of the wound edge is significantly non-uniform, with a red area (relative stress intensity peak > 0.8) corresponding to a local stress concentration area of the wound edge, especially a continuous high tension area (relative stress intensity stable at 0.6-0.8) formed at both ends of the wound edge. Such stress distribution easily leads to excessive activation of local myofibroblasts of the wound edge, and further induces abnormal deposition of collagen. As shown in (c) of FIG. 1, it is proved that after the rotational contraction patch (Rt-MC) is activated, the stress peak decreases by >50%, and the high stress area (red) is dispersed into uniform low stress areas (blue and green). This dynamic redistribution is due to the counteracting effect of the rotational contraction force of the patch on the circumferential stress and the composite stress of the wound edge, achieving the spatiotemporal regulation goal of early regeneration and late scar inhibition from the mechanical aspect. Figure 3 Figure 3 In addition, the in vitro model is used to further verify the rapid closure and clinical operability of the present application. Specifically, in a pig skin circular wound model, the rotational contraction patch (Rt-MC) exhibits excellent clinical translation potential. As shown in (b) of FIG. 1, the stress distribution of the wound edge is significantly non-uniform, with a red area (relative stress intensity peak > 0.8) corresponding to a local stress concentration area of the wound edge, especially a continuous high tension area (relative stress intensity stable at 0.6-0.8) formed at both ends of the wound edge. Such stress distribution easily leads to excessive activation of local myofibroblasts of the wound edge, and further induces abnormal deposition of collagen. As shown in (c) of FIG. 1, it is proved that after the rotational contraction patch (Rt-MC) is activated, the stress peak decreases by >50%, and the high stress area (red) is dispersed into uniform low stress areas (blue and green). This dynamic redistribution is due to the counteracting effect of the rotational contraction force of the patch on the circumferential stress and the composite stress of the wound edge, achieving the spatiotemporal regulation goal of early regeneration and late scar inhibition from the mechanical aspect. Figure 3

[0048] In addition, the in vitro model is used to further verify the rapid closure and clinical operability of the present application. Specifically, in a pig skin circular wound model, the rotational contraction patch (Rt-MC) exhibits excellent clinical translation potential. As shown in (b) of FIG. 1, the stress distribution of the wound edge is significantly non-uniform, with a red area (relative stress intensity peak > 0.8) corresponding to a local stress concentration area of the wound edge, especially a continuous high tension area (relative stress intensity stable at 0.6-0.8) formed at both ends of the wound edge. Such stress distribution easily leads to excessive activation of local myofibroblasts of the wound edge, and further induces abnormal deposition of collagen. As shown in (c) of FIG. 1, it is proved that after the rotational contraction patch (Rt-MC) is activated, the stress peak decreases by >50%, and the high stress area (red) is dispersed into uniform low stress areas (blue and green). This dynamic redistribution is due to the counteracting effect of the rotational contraction force of the patch on the circumferential stress and the composite stress of the wound edge, achieving the spatiotemporal regulation goal of early regeneration and late scar inhibition from the mechanical aspect. Figure 4 ​​(d) in which TEG is a commercial dressing Tegaderm with air and water vapor permeable and antibacterial function; RaC is a simple radial contraction patch; Rt-MC is a medium tension rotary contraction patch; Rt-HC is a high tension rotary contraction patch. The control group wound area increased to 110% within 20 minutes due to natural expansion, while the Rt-MC group was driven by the rotary contraction force to close the wound edge centripetally, and the area was significantly reduced to 70%. This process relies on strong wet-state adhesion (120 kPa) mediated by NHS ester, and stable adhesion without suturing, and the mechanical response is activated within 20 seconds.

[0049] As shown in Figure 5 The application also provides a preparation method of the programmable hydrogel wound dressing with rotary contraction force as described above, comprising the following steps:

[0050] S1, mixing polyvinyl alcohol solution and methacrylated hyaluronic acid solution, adding photoinitiator and acrylic acid-NHS, and completing photopolymerization by ultraviolet irradiation to obtain a wet-state double network hydrogel;

[0051] S2, after the wet-state double network hydrogel is treated by pre-stretching or pre-twisting, drying at 50-60℃ for 40-50 hours to form a shape memory structure, thereby obtaining the programmable hydrogel wound dressing.

[0052] Specifically, in S1, the photoinitiator is LAP, and the addition amount is 0.05-0.2wt%; the wavelength of the ultraviolet light is 365nm, and the irradiation time is 10-20s. In S2, the pre-stretching ratio Δλ of the pre-stretching is 15-50%, and the pre-twist angle Δα of the pre-twisting is 30-45°.

[0053] In addition, the application also provides a use method of the programmable hydrogel wound dressing with rotary contraction force as described above, which is attached to the surface of a wet wound, and after the programmable hydrogel wound dressing absorbs the exudate of the wound, it starts shape recovery and outputs directional mechanical stimulation to the wound edge. Wherein, the directional mechanical stimulation activates YAP and TGF-β / Smad signaling pathways in the early stage of wound healing, and reduces tension to inhibit the activation of myofibroblasts in the later stage of healing. As shown in Figure 5 (a) of FIG. 1, the schematic diagram divides the wound healing process into the inflammation period (corresponding to the initial wound shown in Figure 5 (a) of FIG. 1), the proliferation period and the remodeling period (corresponding to Figure 5The diagram (a) shows three distinct phases: the remodeling phase and the remodeling phase, and quantifies the dynamic tissue changes in each phase (e.g., the peak of fibroblast migration during the proliferative phase and the risk of collagen remodeling during the remodeling phase). This physiological process map provides a core basis for implementing phased programmable mechanical interventions with hydrogel dressings: in the early stage (proliferative phase), moderate tension (1.0–1.6 N) is output through rotational contraction force to activate regeneration signaling pathways, while in the late stage (remodeling phase), mechanical attenuation is used to inhibit fibrosis induced by persistent stress, thus verifying the necessity of dynamic mechanical strategies matching physiological needs at the temporal and spatial control level.

[0054] like Figure 5 As shown in (b), Hippo refers to the Hippo signaling pathway, YAP refers to Yes-associated protein, TGF-β refers to transforming growth factor-β, Smad3 refers to Smad family protein 3, active indicates that the signaling pathway molecules are in a functionally activated state, and α-SMA refers to α-smooth muscle actin. This signaling pathway diagram, through dual fluorescent labeling (YAP nucleoplasmic distribution and Smad3 phosphorylation level), elucidates the precise regulation of fibroblast behavior by external rotational contractile forces: rotational stress, by altering cytoskeletal tension, simultaneously achieves YAP inhibition (reducing nuclear translocation rate >60%) and TGF-β / Smad3 activation (increasing phosphorylation level by 2.1 times). This mechanism demonstrates that the multidirectional mechanical output of hydrogel dressings can break the contradictory balance between regeneration and scar formation, and its rotational mode specificity is superior to traditional linear stretching, providing a molecular biological basis for the dual goals of early healing promotion and late scar inhibition. Figure 6 As shown in (c), the application model intuitively demonstrates the actual application state of the hydrogel patch after it is applied to the skin wound: the patch forms covalent bonds with the amino groups of wound tissue proteins through the NHS ester groups on its surface (adhesion strength reaches 120kPa), ensuring no risk of slippage in a moist environment; at the same time, its spiral structure outputs contraction force along the preset rotation direction (indicated by the arrow) after rehydration, evenly covering the wound edge area, effectively transmitting multi-directional mechanical stimulation to disperse high stress concentration points (such as the wound tip). This integrated design not only achieves precise transmission of mechanical force (such as rotational contraction force of 1.6N), but also adapts to different wound geometry features through customizable shapes (spiral, radial, or strip), solving the limitations of poor wet adhesion performance and non-programmable force field direction of traditional dressings. This further verifies that the adhesion-mechanical coupling mechanism supports rapid bedside operation (activation within 20 seconds) without the need for sutures or external fixation devices; combined with the pigskin experimental data shown in the figure (the wound area decreased by 30% after 20 minutes of patch treatment), it proves that it can effectively inhibit wound expansion and scar risk in real wound environments, providing an engineering basis for the dynamic regulation of the mechanical microenvironment.

[0055] In addition, the present invention also conducted performance tests on programmable hydrogel wound dressings, specifically including:

[0056] like Figure 6 As shown in (b), this figure is the water absorption and swelling curve of the hydrogel, recording the change in the swelling rate of the hydrogel at different time points, intuitively reflecting its water absorption performance in an aqueous environment: as time goes on, the swelling rate of the hydrogel gradually increases and tends to stabilize, demonstrating its ability to quickly respond to wound exudate. This curve verifies the design of the hydrogel of this invention, which can absorb wound exudate and initiate shape recovery, providing performance evidence for its shape memory-driven operation in a moist wound environment. Figure 6 As shown in (c), this figure illustrates the frequency response relationship between the storage modulus (G') and loss modulus (G'') of the modified hydrogel at different frequencies. Red and blue in the figure represent the test results for the unmodified and modified NHS hydrogels, respectively. The results show that the modulus performance of the modified NHS hydrogel in different frequency ranges is not significantly different from that of the unmodified hydrogel, indicating that the preparation of 1-3% wt NHS ester modification does not excessively affect the mechanical properties of the hydrogel. Figure 6 As shown in (d), this figure presents the tensile stress-strain curve of the hydrogel, revealing the differences in mechanical properties of the hydrogel with different component ratios, including key parameters such as fracture strength and elongation at break. The optimized dual-network structure hydrogel exhibits higher fracture strength and better ductility, enabling it to withstand mechanical stress during shape recovery. This result verifies the design of the dual-network structure in this invention, which provides sufficient mechanical support and lays the structural foundation for its effective mechanical force output to promote wound closure. Figure 6 As shown in (e), this figure illustrates the overlap shear test and the shear stress-displacement curves of the modified and unmodified hydrogels. Red and blue in the figure represent the shear stress changes of the unmodified and modified NHS hydrogels, respectively. The experimental results show that the modified NHS hydrogel exhibits significantly higher shear stress with a smaller shear displacement, indicating stronger mechanical strength and better adhesion properties. This characteristic allows the modified NHS hydrogel to provide more stable support and more effective adhesion when applied in wound repair. Figure 6 As shown in (f), this figure illustrates the shear experiment and the shear force-displacement curves of the modified and unmodified hydrogels. The red and blue curves represent the response force changes of the unmodified and modified NHS hydrogels under a 180° shear condition, respectively. The experimental results show that the modified NHS hydrogel exhibits a more stable mechanical response during shearing, especially at larger displacements, where the shear force of the modified hydrogel is significantly higher than that of the unmodified hydrogel, and the mechanical response fluctuation is smaller. This indicates that the modified NHS hydrogel possesses excellent shear resistance and can provide more reliable structural stability in wound repair applications. Figure 6Figure (g) shows a schematic diagram of the tensile test and the tensile stress-displacement curves of the modified and unmodified hydrogels. The blue and red curves represent the stress changes of the unmodified and modified NHS hydrogels during the tensile process, respectively. The experimental results show that the modified NHS hydrogel exhibits significantly higher tensile stress during the tensile process, especially at larger displacements, where the tensile strength of the modified hydrogel is significantly better than that of the unmodified hydrogel. This characteristic enables the modified NHS hydrogel to possess higher tensile strength in wound repair applications, effectively enhancing the mechanical support during wound healing.

[0057] like Figure 6 As shown in (h), this figure presents the test results for interfacial shear force and tensile force. The red circles represent interfacial shear force, and the blue hollow circles represent tensile force. The experimental results show that there is no significant difference (ns) between the modified NHS hydrogel and the unmodified hydrogel in terms of interfacial shear force and tensile force; their mechanical properties remain relatively consistent. This indicates that although the modified NHS hydrogel exhibits better performance in some mechanical tests, its interfacial adhesion and tensile force are comparable to the unmodified hydrogel, demonstrating strong adaptability and the ability to meet the needs of different application scenarios. Figure 6 As shown in (i), ASTM F2255 is the American Society for Testing and Materials (ASTM) standard for testing the adhesive strength of soft tissue repair materials, ASTM F2256 is the ASTM standard for testing the tissue adhesion shear properties of medical materials, and ASTM F2458-05 is the ASTM standard for evaluating the performance of medical adhesives, 2005 edition. This figure shows the results of the overlap shear test, demonstrating the shear stress test results for different tissue types. The red bars in the figure represent skin tissue, and the other colored bars represent heart, liver, kidney, and bone tissue, respectively. The experimental results show that the hydrogel patch has strong adhesion to various organs, with the highest adhesion shear stress in skin tissue, reaching approximately 90 kPa. This result indicates that the hydrogel used in this study has high tissue adhesion ability and can provide good adhesive support in skin wound repair. Figure 7 As shown in (j) of the figure, this figure presents the results of the shear experiment, demonstrating the interfacial adhesion strength test results of different tissue types under 180° shear conditions. The red bars in the figure represent skin tissue, while the other colored bars represent heart, liver, kidney, and bone tissues, respectively. The experimental results show that the interfacial adhesion strength of skin tissue is significantly higher than that of other tissues, reaching approximately 300 J / m², while the interfacial adhesion strength of other tissues also reached a high level. This result indicates that the hydrogel in this study has significant advantages in interfacial adhesion performance with various tissues and is suitable for applications in wound repair. Figure 7 As shown in (k), where " " for statistically significant difference, the figure is the wound closure experiment result, which shows the difference of wound closure force between modified NHS hydrogel and other comparative materials (such as medical tape, gauze and Tegaderm). The red column chart in the figure represents the modified NHS hydrogel, and the blue, black and yellow column charts represent other materials respectively. The experimental results show that the modified NHS hydrogel has a significant advantage in wound closure force, about 6N, which is significantly higher than other comparative materials, and the difference is statistically significant. This result shows that the modified NHS hydrogel can provide stronger closure force in the process of wound repair, and has higher clinical application potential.

[0058] In order to further verify the application of the programmable hydrogel wound dressing with rotary contraction force in regulating the microenvironment of wound surface to promote scarless healing, the following specific animal experiments are further described.

[0059] Firstly, the programmable hydrogel wound dressing of the application is used in a diabetic mouse model to evaluate the wound healing effect, and the results are shown in Figure 7 . Referring to Figure 7 (a), the figure presents the representative wound photos and digital analysis results of different treatment groups (TEG group (using commercial dressing Tegaderm with air-permeable, waterproof and antibacterial functional materials), RaC group (simple radial contraction patch), Rt-HC group (high-tension rotary contraction patch), Rt-MC group (medium-tension rotary contraction patch)) in 5mm full-thickness skin defect model of diabetic mouse back at 0, 4, 8 and 16 days, which directly shows the difference of wound closure process in each group: the wound closure speed of Rt-MC group is significantly faster than that of other groups over time, especially at 8 and 16 days, and the wound integrity is better. This result directly reflects the promoting effect of the hydrogel wound dressing of the application in chronic wound repair, and provides macroscopic evidence for its effect of regulating the microenvironment of wound surface.

[0060] Referring to Figure 7 (b), the figure is the quantitative result of wound area change over time in different treatment groups, which clearly presents the wound healing rate of each group through data curve: the wound area of Rt-MC group at each time point is smaller than that of control group and other mode groups, and the wound area closure rate at 16 days is 83.4%±3.1%, which is significantly higher than that of TEG group (48.2%±5.6%). This quantitative data further verifies the advantage of hydrogel dressing with medium rotary contraction mode in promoting wound closure efficiency, and supports its effective regulation of the microenvironment of wound surface. Referring to Figure 8Figure 8 shows the H&E staining results of the wound tissues of different treatment groups on the 8th day and the 16th day, including the magnified images of the re-epithelialization front, presenting the microscopic structure of tissue regeneration: the epidermal layer of the Rt-MC group has better continuity, the dermal layer has more ordered cell arrangement, the re-epithelialization front has more obvious advancement, and the inflammatory cell infiltration is less. This result proves that the patch of the application can improve the microenvironment of the wound and promote the ordered regeneration of the tissue, laying the foundation for scarless healing. Figure 9 Figure 9 shows the quantitative analysis data of the re-epithelialization degree of the wounds of different treatment groups, comparing the integrity of the epidermal regeneration of each group by statistical methods: the re-epithelialization degree of the Rt-MC group on the 8th day and the 16th day reaches 65% and 92% respectively, which is significantly higher than that of other groups. This data directly reflects that the hydrogel patch of the application can effectively promote the epidermal regeneration and wound re-epithelialization by regulating the microenvironment of the wound, further verifying its application value in promoting scarless healing.

[0061] Secondly, the programmable hydrogel wound patch of the application was subjected to wound healing mechanism regulation under the regulation of the rotating shrinkage hydrogel patch, and the results are shown in Figure 8 and Figure 9 Figure 10 shows the Masson trichrome staining results of the wound tissues of different treatment groups on the 8th day and the 16th day, presenting the distribution and arrangement of collagen fibers: the collagen fibers of the Rt-MC group (moderate rotating shrinkage mode) are more regularly arranged and more evenly distributed, and are closer to the collagen structure of normal tissue, while the control group and other mode groups have phenomena of disordered collagen arrangement and uneven deposition. This result directly reflects that the hydrogel patch of the application can improve the collagen remodeling process by regulating the microenvironment of the wound, providing histological evidence for promoting scarless healing.

[0062] In addition, the expression of angiogenesis, fibroblast activity and related signal pathway molecules was also demonstrated by CD31, a-SMA, DAPI, TGF-β, YAP and other markers: the Rt-MC group has more CD31 positive blood vessels, lower a-SMA expression (indicating that the activation of myofibroblasts is inhibited), and the nuclear translocation of TGF-β and YAP is more in line with the needs of each stage of wound healing. This image reveals the mechanism of the hydrogel patch in regulating the microenvironment of the wound from the cellular and molecular levels, supporting its dual effect of promoting tissue regeneration and inhibiting scar formation. Refer to Figure 10 (a), (b), (c) and Figure 11As shown in (a), (b), and (c), these figures present quantitative analysis data of IL-6, TNF-α, CD31, α-SMA, TGF-β, and YAP. Statistical methods were used to compare the differences in molecular expression among different treatment groups: the Rt-MC group showed significantly lower levels of pro-inflammatory factors IL-6 and TNF-α, higher CD31-positive vessel density, lower α-SMA expression, and TGF-β and YAP expression and activation levels were more conducive to wound healing. These quantitative results further validate that hydrogel dressings can optimize the wound microenvironment by regulating inflammatory responses, promoting angiogenesis, and modulating key signaling pathways, providing strong molecular-level support for its technical efficacy in promoting scarless healing.

[0063] Finally, the programmable hydrogel wound dressing of this invention was applied to a rabbit ear hypertrophic scar model for long-term evaluation of scar remodeling and tissue regeneration. The results are as follows: Figure 10 and Figure 10 As shown. (Refer to...) Figure 10 Figure (a) shows the wound healing appearance of each treatment group in the rabbit ear hypertrophic scar model at weeks 0, 2, 4, 6, and 8, visually demonstrating the long-term changes in scar formation: the Rt-MC group (moderate rotational contraction pattern) showed significantly lower scar hyperplasia than the control group and other pattern groups, especially at weeks 6-8, where the scar color was closer to normal skin and the elevation was less pronounced. This result directly demonstrates the role of the hydrogel dressing of this invention in long-term inhibition of scar formation, providing macroscopic evidence for its regulation of the wound microenvironment to promote scarless healing. Figure 11 As shown in (b), this figure presents the H&E staining results of wound tissues from different treatment groups at weeks 4 and 8, revealing differences in dermal structure repair and scar thickness: the dermal structure of the Rt-MC group was closer to normal tissue, the scar thickness was significantly thinner than the control group, and there was less inflammatory cell infiltration. This histological result validates that hydrogel dressings can improve the wound microenvironment, reduce abnormal tissue proliferation, and support its technical effect of inhibiting scar formation. Figure 11 As shown in (c), this figure presents the Masson trichrome staining results of wound tissues from different treatment groups, demonstrating the distribution and regularity of collagen fibers: the collagen fibers in the Rt-MC group were more orderly and oriented, similar to the collagen structure of normal skin, while the collagen fibers in the control group were disordered and intertwined. This result demonstrates the optimizing effect of hydrogel dressings on the wound microenvironment from the perspective of collagen remodeling, providing a structural basis for scarless healing. Figure 11As shown in (a), this figure presents the results of SiriusRed staining under polarized light, reflecting the maturity of collagen fibers and the orderliness of tissue structure: the ratio of type I to type III collagen in the Rt-MC group is closer to that of normal tissue, and the direction of collagen fibers is more regular, while the collagen maturity in the control group is lower and the arrangement is disordered. This result further confirms that hydrogel dressings can promote normal collagen maturation and arrangement by regulating the wound microenvironment, which helps to reduce scar formation.

[0064] like Figure 12 As shown in (b) of the figure, this figure presents the quantitative analysis results of CD31 signal intensity, reflecting the status of wound angiogenesis: the CD31-positive vessel density in the Rt-MC group was closer to normal levels in the later stages of healing, ensuring both the blood supply required for tissue repair and avoiding scar hyperplasia caused by excessive vascularization. This result reveals the mechanism by which hydrogel dressings optimize the wound microenvironment by regulating angiogenesis, contributing to an understanding of its mechanism of action in inhibiting scarring. Figure 13 As shown in (c), this figure presents the quantitative analysis results of α-SMA signal intensity, reflecting the degree of myofibroblast activation: the α-SMA expression level in the Rt-MC group was significantly lower than that in the control group, especially in weeks 4-8, indicating that myofibroblast activation was effectively inhibited. This result explains the mechanism by which hydrogel dressing inhibits scar formation at the cellular level, namely, by regulating the wound microenvironment to reduce excessive proliferation and contraction of myofibroblasts, thereby reducing the risk of scar hyperplasia.

[0065] In addition, this invention also provides transcriptomic analysis revealing the molecular mechanism by which hydrogel patches promote healing and reduce scarring through mechanical regulation, as shown in the following results. Figure 14 , Figure 15 , Figure 12 and Figure 12 As shown. Among them, in Figure 12 In (a) and (b), Log2FPKM is the logarithmically mapped reading per kilobase exon per million fragments, used to quantify gene expression levels; log2FC is the logarithmically fold change in expression, used to measure the degree of difference in gene expression between two groups, with positive values ​​indicating "upregulated gene (UP)" and negative values ​​indicating "downregulated gene (DOWN)"; -log 10 (Adjusted P-value) is the negative logarithm of the adjusted P-value, used to assess the statistical significance of the difference; Padj is the adjusted P-value, used to exclude false positives from multiple tests; NOT represents genes with no significant difference. (Refer to...) Figure 13Figure (a) shows a circular heatmap of whole-gene expression in wound tissue at week 4, illustrating the differences in gene expression among different treatment groups (such as the Rt-MC group, RaC group, and control group). The color intensity visually represents the level of gene expression: the Rt-MC group (moderate rotational contraction pattern) exhibited a specific expression pattern in gene clusters related to wound healing, collagen metabolism, and inflammation regulation, significantly distinguishing it from other groups. This result reveals the molecular basis of hydrogel dressings regulating the wound microenvironment at the genomic level, providing broad-spectrum gene expression evidence for its role in promoting scarless healing. (See reference...) Figure 14 Figure (b) shows a differential gene volcano plot between the Rt-MC and RaC groups, presenting significant differences in gene expression between the two groups in a scatter plot format: red dots represent significantly upregulated genes, and blue dots represent significantly downregulated genes. Genes related to the TGF-β and Hippo-YAP pathways show markedly different expression. This plot precisely locates key regulatory genes under different mechanical modes, providing target references for elucidating the molecular mechanism by which hydrogel dressings influence scar formation through specific mechanical stimulation.

[0066] Among them, Figure 13In the ordinate of the graph, biological processes (BP) include: multicellular organism development for development of multicellular organisms; skeletal system development for development of skeletal systems; animal organ morphogenesis for animal organ morphogenesis; tissue development for tissue development; system development for system development; regulation of cellular response to growth factor stimulus for regulation of cellular response to growth factor stimulus; anatomical structure morphogenesis for anatomical structure morphogenesis; animal organ development for animal organ development; cartilage development for cartilage development; collagen fibril organization for collagen fibril organization; molecular function (MF) includes: calcium ion binding for calcium ion binding; extracellular matrix structural constituent for extracellular matrix structural constituent; integrin binding for integrin binding; procollagen-proline dioxygenase activity for procollagen-proline dioxygenase activity; cell adhesion molecule binding for cell adhesion molecule binding; peptidyl-proline dioxygenase activity for peptidyl-proline dioxygenase activity; frizzled binding for frizzled binding; signaling receptor binding for signaling receptor binding; chemoattractant activity for chemoattractant activity; organic acid binding for organic acid binding; cellular component (CC) includes: extracellular matrix for extracellular matrix; external encapsulating structure for external encapsulating structure; collagen trimer for collagen trimer; extracellular region for extracellular region; collagen-containing extracellular matrix for collagen-containing extracellular matrix; cell periphery for cell periphery; FACIT collagen trimer for FACIT collagen trimer;EC for extracellular space; microfibril for microfibril; fibrillar collagen trimer for fibrillar collagen trimer. Gene number is the number of genes involved in the corresponding GO term, and Rich Factor is the ratio of the number of genes involved in a certain GO term in the differential genes to the number of genes involved in the GO term in the background genes, and the higher the value, the higher the enrichment degree of the GO term; -log10(p.value) is the negative logarithm of P value, which is used to represent the statistical reliability of the enrichment result. Figure 13ECM-receptor interaction is extracellular matrix-receptor interaction, involved in the binding of extracellular matrix and cell surface receptors, regulating cell adhesion, migration, etc. Focal adhesion is focal adhesion, a key structure for cell adhesion to extracellular matrix, involved in mechanical force conduction and signal transduction. TGF-beta signaling pathway is transforming growth factor-beta signaling pathway, which plays a core regulatory role in cell proliferation, differentiation, apoptosis and tissue repair. PI3K-Akt signaling pathway is phosphatidylinositol 3-kinase-protein kinase B signaling pathway, involved in cell survival, proliferation, metabolism and other biological processes. Cell cycle is cell cycle, the periodic process from the end of one division to the end of the next division, regulating cell proliferation. Regulation of actin cytoskeleton is actin cytoskeleton regulation, actin is an important component of the cytoskeleton, its dynamic regulation affects cell morphology, movement and signal transduction. Proteoglycans in cancer is protein glycan in cancer, which plays a role in tumor occurrence, invasion and metastasis. Malaria is malaria, a disease caused by Plasmodium infection, involving infection-related molecular mechanisms. Human papillomavirus infection is human papillomavirus infection, related to viral carcinogenic mechanisms. Hippo signaling pathway is Hippo signaling pathway, regulating cell proliferation, apoptosis and organ size, closely related to tissue regeneration and tumorigenesis. Hippo signaling pathway-multiple species is multiple species Hippo signaling pathway, a conservative analysis of the Hippo pathway in different species. Complement and coagulation cascades are complement and coagulation cascades, involved in immune defense and hemostasis processes. Biosynthesis of nucleotide sugars is nucleotide sugar biosynthesis, nucleotide sugar is a precursor for processes such as glycosylation. Staphylococcus aureus infection is Staphylococcus aureus infection, related to bacterial infection-related signaling pathways. Melanoma is melanoma, a type of skin cancer, involving molecular mechanisms of tumorigenesis. Amoebiasis is amoebiasis, an infectious disease caused by amoeba. Cocaine addiction is cocaine addiction, related to addiction-related neurobiology pathways. Regulation of lipolysis in adipocytes is regulation of lipolysis in adipocytes, the regulation of triglyceride decomposition in adipocytes.Gastric cancer is stomach cancer, the molecular pathway of gastric cancer development, the rest is with; Figure 14 Consistency is maintained.

[0067] Referring to Figure 15 and ​ , these two figures are the results of GO enrichment analysis and KEGG pathway analysis, focusing on the biological processes and signal pathways involved in differential genes: GO analysis shows that differential genes are mainly enriched in ECM remodeling, collagen fiber assembly and other processes; KEGG analysis highlights the significant activation of TGF-β signaling pathway and Hippo-YAP signaling pathway. These results clarify the core molecular pathways of hydrogel dressing in regulating wound microenvironment from the functional level, and support the technical principle of affecting cell behavior through mechanical stimulation. Referring to ​ (a), (b) and (c) in, these figures are the immunofluorescence images and quantitative results of TGF-β and YAP, showing the changes in expression and localization at the protein level: the expression of TGF-β in the Rt-MC group is moderate in the early stage of wound healing to promote regeneration, and gradually decreases in the later stage to reduce scar; the nuclear translocation rate of YAP shows a phased change, which matches the time sequence regulation of mechanical stimulation, and the quantitative data shows that its expression level is negatively correlated with the scar inhibition effect. These results verify the activation mode of the key signal pathway from the protein level, and directly confirm the molecular mechanism of hydrogel dressing in optimizing the wound microenvironment by regulating the TGF-β / YAP pathway.

[0068] Therefore, the programmable hydrogel wound dressing with rotational contractile force and its application described above realize dynamic and accurate regulation of stress on the wound edge by constructing a double-network hydrogel structure and an NHS ester functionalized surface; at the same time, it can also output direction-controllable and strength-adjustable mechanical force according to the shape and healing stage of the wound, maintaining excellent tissue adhesion while taking into account the dual effects of early regeneration promotion and late scar inhibition, solving the problems of passivity, single effect and instability of the wet environment in the prior art.

Claims

1. A programmable hydrogel wound dressing with rotational contraction force, characterized in that, include: The dual-network hydrogel body is composed of a first network and a second network; the first network is a chemically cross-linked methacrylamide hyaluronic acid network, which forms a cross-linked network structure through photopolymerization; the second network is a physically cross-linked polyvinyl alcohol network, which forms instantaneous cross-linking points with crystalline regions through hydrogen bonds, giving the hydrogel shape memory properties. The surface of the dual-network hydrogel host is modified with N-hydroxysuccinimide ester functional groups, which can form covalent bonds with the amino groups of wound tissue proteins; The dual-network hydrogel body is dried and shaped into a preset shape after pre-stretching or pre-twisting treatment. After absorbing water, it restores its initial shape and outputs a mechanical force of rotational contraction. The N-hydroxysuccinimide ester functional group is achieved by introducing acrylic acid-NHS comonomer, and the amount of acrylic acid-NHS added is 1~3wt%.

2. The programmable hydrogel wound dressing with rotational contraction force according to claim 1, characterized in that, The concentration of methacrylamide hyaluronic acid in the first network is 3-5 vol%, and the concentration of polyvinyl alcohol in the second network is 8-12 wt%.

3. The programmable hydrogel wound dressing with rotational contraction force according to claim 1, characterized in that, The preset shape includes one or more of spiral, radial, and strip shapes, and the corresponding output mechanical force mode includes one or more of radial contraction, rotational contraction, and tension relief.

4. A method for preparing a programmable hydrogel wound dressing with rotational contraction force according to any one of claims 1 to 3, characterized in that, Includes the following steps: S1. Mix polyvinyl alcohol solution with methacrylamide hyaluronic acid solution, add photoinitiator and acrylic acid-NHS, and complete photopolymerization by ultraviolet light irradiation to obtain wet double network hydrogel. S2. After pre-stretching or pre-twisting the wet dual-network hydrogel, dry it at 50~60℃ for 40~50 hours to form a shape memory structure, thereby obtaining the programmable hydrogel wound dressing.

5. The method for preparing a programmable hydrogel wound dressing with rotational contraction force according to claim 4, characterized in that, In S1, the photoinitiator is LAP, and the addition amount is 0.05~0.2wt%; the ultraviolet light wavelength is 365nm, and the irradiation time is 10~20s.

6. The method for preparing a programmable hydrogel wound dressing with rotational contraction force according to claim 4, characterized in that, In S2, the pre-stretch ratio Δλ is 15~50%, and the pre-torsion angle Δα is 30~45°.

7. A method of using a programmable hydrogel wound dressing with rotational contraction force according to any one of claims 1 to 3, characterized in that, The programmable hydrogel wound dressing is applied to the surface of a moist wound. After absorbing the exudate from the wound, the programmable hydrogel wound dressing initiates shape recovery and outputs directional mechanical stimulation to the wound edge.

8. The method of using a programmable hydrogel wound dressing with rotational contraction force according to claim 7, characterized in that, The directional mechanical stimulation activates the YAP and TGF-β / Smad signaling pathways in the early stage of wound healing and reduces tension in the later stage of healing to inhibit myofibroblast activation.

9. An application of a programmable hydrogel wound dressing with rotational contraction force according to any one of claims 1 to 3, characterized in that, Specifically, it is used to regulate the wound microenvironment and promote scarless healing.

Images