Piezoelectric antibacterial supramolecular self-gelling hemostatic powder, method of preparation and use thereof

Abstract

The present application relates to piezoelectric antibacterial supramolecular self-gelling hemostatic powder and its preparation method and application, belong to biomedical material and wound repair technical field. The piezoelectric antibacterial supramolecular self-gelling hemostatic powder is obtained by drying and grinding hydrogel, wherein the hydrogel is uniformly dispersed in the network structure formed by supramolecular interaction of nano clay and piezoelectric nanoparticles in zwitterionic polymer and polyacrylic acid;The zwitterionic polymer is [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide. The hemostatic powder has excellent powder-gel reversibility and controllable ultrasonic responsiveness, which provides a better solution for acute bleeding treatment and infection wound healing.

Description

Technical Field

[0001] This invention relates to piezoelectric antibacterial supramolecular self-gelling hemostatic powder, its preparation method and application, belonging to the field of biomedical materials and wound repair technology. Background Technology

[0002] Uncontrolled bleeding and subsequent infection-induced wound healing caused by severe trauma have become a major challenge in global public health, resulting in more than 5 million deaths worldwide each year. While traditional surgical suturing can effectively stop bleeding, it has inherent drawbacks such as a high risk of secondary trauma, an increased postoperative infection rate (approximately 37%), and scar formation. Furthermore, commonly used hemostatic materials often lack sufficient adhesion to adapt to irregular wound surfaces, leading to a significant decrease in hemostatic efficiency. Achieving a dynamic balance between rapid hemostasis and controlled repair in complex trauma environments has become a pressing scientific challenge in the fields of trauma emergency care and regenerative medicine.

[0003] Adhesive hydrogels, due to their excellent adhesion, mechanical properties, and biocompatibility, have been widely used in hemostatic agents, wound dressings, and wearable devices. Adhesive hydrogels are mainly divided into two categories: pre-formed adhesive hydrogels and in-situ formed adhesive hydrogels. Pre-formed adhesive hydrogels require polymers to diffuse through water at the tissue interface to achieve bonding; however, most of these hydrogels rely on chemical cross-linking to stabilize their structure, resulting in weak adhesion between the tissue and the hydrogel. Self-gelling powders in in-situ formed adhesive hydrogels exhibit significant advantages due to their wet adhesion properties and rapid molding capabilities. A recent report indicates that PEI / PAA / QCS self-gelling powders can not only rapidly stop bleeding but also promote the healing of full-thickness skin wounds. However, existing self-gelling powders still lack applications in treating bacterially infected wounds, which is a common and challenging problem in the treatment of severe trauma.

[0004] Sonodynamic therapy (SPT) is an excellent non-antibiotic therapy that utilizes ultrasound and sonosensitizers to generate sufficient reactive oxygen species (ROS) to eliminate bacteria, and has recently become a promising approach for treating bacterial wound infections. Barium titanate (BaTiO3, BTO), as a sonosensitizer with good piezoelectric effects, has made significant progress in antibacterial treatment. Its principle is that BTO can immediately generate an internal electric field and surface potential under ultrasound, thereby triggering a redox reaction to produce ROS for antibacterial treatment. It is worth noting that although increasing local ROS levels helps to clear bacterial infections, excessive ROS can cause similar oxidative damage to adjacent cells and tissues, leading to local homeostasis imbalance and hindering subsequent repair. Therefore, precise regulation of ROS levels is crucial. Currently, the commonly used method for regulating ROS is the use of antioxidants; however, determining the appropriate antioxidant dosage is complex, and long-term use of antioxidants may interfere with normal cell signaling pathways, potentially causing adverse reactions. Recently, controlling ultrasound to regulate ROS generation has shown particular potential. Ultrasound allows for non-invasive and controllable adjustment of ROS levels through physical stimulation, optimizing cell proliferation and tissue regeneration while reducing adverse reactions. However, no studies have clearly defined the dose-response relationship of ultrasound dosage, frequency, and time. Therefore, there is an urgent need to develop supramolecular self-gelling piezoelectric powders with adjustable ultrasound response for the precise treatment of complex and difficult-to-heal wounds. Summary of the Invention

[0005] To address the problems of slow hemostasis, high infection risk, and long healing time in existing technologies, this invention provides a piezoelectric antibacterial supramolecular self-gel hemostatic powder, its preparation method, and its applications. This invention prepares a piezoelectric antibacterial supramolecular self-gel hemostatic powder by dry annealing and grinding a precursor solution containing polyacrylic acid, zwitterionic polymers, nanoclay, and piezoelectric nanoparticles. This powder exhibits excellent powder-gel reversibility and adjustable ultrasonic response, solving the problems of rapid and effective hemostasis in acute bleeding, especially in irregularly shaped, incompressible, and high-pressure arterial wounds, as well as low healing efficiency in bacterial infected wounds. Furthermore, it improves upon the shortcomings of existing products, such as poor tissue adhesion, poor biocompatibility, or limited functionality, providing a superior solution for the treatment of acute bleeding and the healing of infected wounds.

[0006] The piezoelectric antibacterial supramolecular self-gelling hemostatic powder is obtained by drying and grinding hydrogel.

[0007] The hydrogel consists of nano-clay and piezoelectric nanoparticles uniformly dispersed in a network structure formed by supramolecular interactions between zwitterionic polymers and polyacrylic acid.

[0008] The zwitterionic polymer is [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide (DMAPS).

[0009] Furthermore, the supramolecular interaction is one or both of hydrogen bonding and electrostatic interaction.

[0010] Furthermore, the hemostatic powder obtained after grinding has a particle size of 100 mesh or larger.

[0011] Preferably, the nanoclay is Laponite XLS.

[0012] Preferably, the piezoelectric nanoparticles are barium titanate.

[0013] In the method described in this invention, the hydrogel is prepared by polymerization reaction of nano-clay, zwitterionic polymer, polyacrylic acid, piezoelectric nanoparticles and deionized water.

[0014] Furthermore, the mass ratio of the nanoclay, zwitterionic polymer, polyacrylic acid, and piezoelectric nanoparticles is 1~3 : 25 : 1.5~3 : 0.015~0.025.

[0015] Furthermore, the mass-to-volume ratio of the nano-clay to deionized water is 1~3 g : 10 mL.

[0016] Another object of the present invention is to provide a method for preparing the above-mentioned hemostatic powder, comprising the following steps: under stirring conditions, zwitterionic polymer, polyacrylic acid and piezoelectric nanoparticles are added sequentially to a nano-clay suspension, stirred and mixed, and then subjected to a polymerization reaction, followed by drying and grinding to obtain the hemostatic powder.

[0017] In the above technical solution, the polymerization reaction conditions are: reaction at 60°C for 45 min.

[0018] In the above technical solution, the stirring rate is 500 rpm and the stirring time is 10 min.

[0019] In the above technical solution, the drying conditions are drying in an oven at 60°C for 24 hours.

[0020] In the above technical solution, a ball mill is used for grinding, with a ball-to-material ratio of 10:1, and grinding is carried out at 300 rpm for 2 hours.

[0021] Furthermore, the nano-clay suspension is prepared by adding nano-clay to deionized water and ultrasonically dispersing it for 10 min.

[0022] A preferred embodiment of the present invention includes the following steps:

[0023] Step 1: Add nano-clay to deionized water and disperse it by ultrasonication to ensure that the nano-clay particles are evenly distributed in the deionized water, thus avoiding agglomeration and finally preparing a nano-clay aqueous suspension with uniform texture.

[0024] Step 2: After the aqueous suspension in Step 1 has stabilized, start the stirring equipment. Under continuous stirring, add the zwitterionic polymer, polyacrylic acid and piezoelectric nanoparticles to the aqueous suspension in sequence. Keep stirring for a period of time to ensure that the materials can fully contact and mix to form a homogeneous mixed solution.

[0025] Step 3: Carefully pour the mixed solution obtained in Step 2 into the selected mold, ensuring that the solution can fill the mold cavity evenly. Then place it in a temperature-controlled device, set specific temperature parameters, and allow the mixed solution to undergo a polymerization reaction. After the reaction is complete, a supramolecular hydrogel with a stable structure is obtained.

[0026] Step 4: Remove the hydrogel obtained in Step 3 from the mold and place it in a drying device with a set temperature for drying to remove the moisture from the hydrogel; after drying, use a grinding device to grind the dried hydrogel into powder with a particle size of 100 mesh or more, which is the piezoelectric antibacterial supramolecular self-gel hemostatic (DPNB) powder.

[0027] Another object of the present invention is to provide the application of the above-described hemostatic powder or the hemostatic powder prepared by the above method in the preparation of materials for treating acute bleeding.

[0028] Another object of the present invention is to provide the application of the above-mentioned hemostatic powder or the hemostatic powder prepared by the above method in the preparation of wound healing materials.

[0029] Furthermore, the wound is a bacterial infection wound.

[0030] The non-covalent interactions in the crosslinking of the supramolecular hydrogel described in this invention can be flexibly broken and recombine, achieving excellent powder-gel reversibility. This allows the supramolecular hydrogel to rapidly recover and reform a stable network structure under environmental conditions (water / blood) after its structure is disrupted (such as during dry annealing and grinding), making it easier to store and transport. It also provides a flexible and efficient solution for acute bleeding and irregular wound healing scenarios, significantly enhancing its practical value and adaptability.

[0031] The supramolecular self-gelling hemostatic powder of this invention has adjustable ultrasonic responsiveness. When used in combination with sonodynamic therapy, it utilizes the synergistic effect of ultrasound waves of different intensities to efficiently clear wound bacteria in the early stage and promote cell proliferation, migration, and tissue regeneration in the later stage, achieving highly effective antibacterial treatment and accelerated healing of wounds prone to infection after hemostasis. The specific combined use includes the following steps:

[0032] Step 1: Pre-treat the infected wound. After removing foreign objects from the surface, apply supramolecular self-gelling hemostatic powder evenly to the wound surface, allowing it to fully contact the wound and form a hydrogel in situ, creating a physical barrier and adsorbing bacteria.

[0033] Step 2: Implement the first stage of ultrasound therapy (antibacterial stage): Use high-intensity ultrasound to irradiate the wound area. Utilize the ultrasound to trigger the piezoelectric catalytic effect of DPNB powder to generate reactive oxygen species (ROS) to kill bacteria at the wound site. Perform the treatment once a day until the bacteria are eliminated.

[0034] Step 3: After completing the first stage of treatment, switch to the second stage of ultrasound treatment (healing promotion stage): Low-intensity ultrasound is used to irradiate the wound. Through the synergistic effect of mechanical stimulation and piezoelectric effect, it promotes the proliferation, migration and angiogenesis of fibroblasts, accelerates the formation of granulation tissue and epithelialization, and is performed once a day until the wound heals.

[0035] Preferably, in step 1, the amount of DPNB powder used is 20-30 mg per square centimeter of wound surface, and the hydrogel formation time is controlled within 3 seconds, so as to quickly seal the wound and establish an antibacterial-repair microenvironment.

[0036] Preferably, in step 2, the parameters for the first stage of ultrasound treatment are: power 0.9 W / cm². 2 The irradiation frequency was 3 MHz, the duty cycle was 50%, and the daily irradiation time was 10 minutes for 3 consecutive days. This stage can achieve a bactericidal rate of over 93% for both Escherichia coli and Staphylococcus aureus without affecting cell proliferation and migration.

[0037] Preferably, in step 3, the parameters for the second stage of ultrasound treatment are: power 0.3 W / cm². 2 The irradiation frequency was 3 MHz, the duty cycle was 50%, and the daily irradiation time was 10 min, from day 3 to day 14. During this phase, the number of fibroblasts proliferated was approximately 2 times higher than that of the control group, the cell migration rate was approximately 3 times higher, and the number of angiogenesis was 5.7 times higher than that of the control group.

[0038] Furthermore, the above-mentioned technical solution allows for regular observation of wound healing, including the amount of exudate, wound closure rate, and inflammatory response. Ultrasonic treatment parameters can be adjusted according to the healing progress to ensure a balance between antibacterial effect and tissue repair.

[0039] Preferably, the wound observation cycle is once a day, and the closure rate is recorded by wound photos. On the 3rd, 7th and 14th days, the number of bacteria (CFU count), collagen deposition rate and epidermal thickness are detected. On the 14th day, the wound closure rate of the DPNB segmented ultrasound group can reach 96.3%, the epidermal thickness is close to that of normal skin (99.7 μm), and the collagen deposition rate reaches 67.2%.

[0040] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0041] The supramolecular self-gelling hemostatic powder of this invention utilizes the synergistic effect of nano-clay, zwitterionic polymer, polyacrylic acid (PAA), and piezoelectric nanoparticles to rapidly form a hydrogel in situ upon contact with blood through supramolecular interactions. This not only quickly seals bleeding points but also significantly enhances adhesion to tissues by forming hydrogen bonds and electrostatic attraction with tissue surfaces through free -COOH groups, positively charged quaternary ammonium salt groups, and negatively charged sulfonic acid groups. Simultaneously, it forms a stable physical barrier to resist blood pressure, effectively addressing various complex bleeding scenarios. It has significant advantages in rapid hemostasis and adaptation to complex wounds, solving the problems of slow hemostasis and poor treatment effect on irregularly shaped or high-pressure arterial bleeding wounds that are common in existing hemostatic materials.

[0042] The DPNB powder described in this invention has piezoelectric properties, and its combination with spatiotemporal acoustic dynamic modulation therapy can achieve highly efficient synergy between antibacterial and healing effects. Specifically, in the early stage, high-intensity ultrasound is used to trigger the piezoelectric nanoparticles in the DPNB powder to generate a piezoelectric effect, producing reactive oxygen species (ROS) to efficiently kill bacteria in the wound. In the later stage, low-intensity ultrasound is switched to utilize its mechanical stimulation and piezoelectric effect to synergistically promote fibroblast proliferation, migration, and angiogenesis, accelerating tissue regeneration and overcoming the limitations of insufficient antibacterial effect or long healing cycle in existing technologies. Attached Figure Description

[0043] Figure 1 The diagram shows the structural test results of the supramolecular hydrogel and hemostatic powder obtained in Example 1. In the diagram, a is a schematic diagram of the rapid self-gelation of the hemostatic powder to form various shapes, b is a diagram of the microscopic self-gelation process of the hemostatic powder, c is a diagram of the scanning rheological test results of the hemostatic powder, d is a diagram of the frequency scanning rheological test results of the hemostatic powder, and e is a diagram of the FTIR test results of the supramolecular hydrogel.

[0044] Figure 2 The figures show the adhesion test results of supramolecular self-gel powder, where a is the adhesion test result of supramolecular hydrogels with different PAA contents on pig skin, and b is the adhesion test result of the supramolecular hydrogel obtained in Example 1 on different tissues.

[0045] Figure 3 The figures show the burst pressure test results of supramolecular self-gel powder, where a is a schematic diagram of the burst pressure test and b is a burst pressure test result of DPNB powder with different PAA contents.

[0046] Figure 4 The images show the results of a coagulation experiment using supramolecular self-gelling powder. In the image, a is a photograph of the coagulation experiment using DPNB powder, and b is a graph showing the coagulation time results of DPNB powder.

[0047] Figure 5 SEM image of supramolecular self-gel powder adhesion and aggregation.

[0048] Figure 6 The graph shows the red blood cell adhesion rate of the supramolecular self-gelling powder.

[0049] Figure 7 The images show the results of using supramolecular self-gelling powder for hemostasis in rat liver. In the images, a is a schematic diagram and photograph of DPNB powder for hemostasis in rat liver, b is a result of the amount of bleeding in rat liver treated with DPNB powder, and c is a result of the hemostasis time in rat liver treated with DPNB powder.

[0050] Figure 8 The images show the results of using supramolecular self-gelling powder for hemostasis of the femoral artery in rats. In the images, a is a schematic diagram and photograph of DPNB powder for hemostasis of the femoral artery in rats, b is a result of the amount of bleeding in the femoral artery in rats treated with DPNB powder, and c is a result of the hemostasis time in the femoral artery in rats treated with DPNB powder.

[0051] Figure 9 The images show the results of using supramolecular self-gelling powder for hemostasis in rat tails. In the images, a is a schematic diagram and photograph of DPNB powder for hemostasis in rat tails, b is a result of the amount of bleeding in rat tails treated with DPNB powder, and c is a result of the hemostasis time in rat tails treated with DPNB powder.

[0052] Figure 10 The graph shows the ESR test results of supramolecular self-gelling powder, where a represents the •OH formation results and b represents... 1 O2 generation result image.

[0053] Figure 11 The graph shows the ROS content test results for supramolecular self-gel powder. In graph a, TA measurement shows the •OH generation content; in graph b, SOSG measurement shows the ROS content. 1 O2 production content graph.

[0054] Figure 12 The graphs show the ROS formation results of supramolecular self-gel powder under different ultrasonic powers. In graph a, •OH formation results are shown under different ultrasonic powers; in graph b, •OH formation results are shown under different ultrasonic powers. 1O2 generation result image.

[0055] Figure 13 Antibacterial properties of supramolecular self-gelling powders with different components.

[0056] Figure 14 The graph shows the antibacterial rate of supramolecular self-gel powders with different components. In the graph, a represents the bactericidal rate of different treatment groups against Escherichia coli, and b represents the bactericidal rate of different treatment groups against Staphylococcus aureus.

[0057] Figure 15 The image shows the antibacterial activity of supramolecular self-gelling powder under different ultrasonic powers.

[0058] Figure 16 The graphs show the antibacterial rates of supramolecular self-gelling powder under different ultrasonic powers. In graph a, DPNB powder has a bactericidal rate against Escherichia coli under different ultrasonic powers, and in graph b, DPNB powder has a bactericidal rate against Staphylococcus aureus under different ultrasonic powers.

[0059] Figure 17 The image shows the cell proliferation results of supramolecular self-gel powders with different components.

[0060] Figure 18 The graph shows the relative cell proliferation results for supramolecular self-gel powders with different components.

[0061] Figure 19 The image shows the cell proliferation results of supramolecular self-gel powder under different ultrasonic powers.

[0062] Figure 20 The graph shows the relative cell proliferation results of supramolecular self-gel powder under different ultrasonic powers.

[0063] Figure 21 This image shows the cell migration results of supramolecular self-gelling powders with different components.

[0064] Figure 22 The graph shows the cell migration gap area ratio of supramolecular self-gel powders with different components.

[0065] Figure 23 The image shows the cell migration results of supramolecular self-gel powder under different ultrasonic powers.

[0066] Figure 24 The figure shows the cell migration gap area ratio of supramolecular self-gel powder under different ultrasonic powers.

[0067] Figure 25 This image shows the results of using supramolecular self-gel powder for wound healing in vivo.

[0068] Figure 26 This is a graph showing the changes in in vivo wound area under treatment with supramolecular self-gel powder.

[0069] Figure 27 The graph shows the in vivo wound closure rate results under supramolecular self-gel powder treatment.

[0070] Figure 28 The image shows the H&E staining results of wound tissue after treatment with supramolecular self-gelling powder.

[0071] Figure 29 This image shows the result of wound epidermal thickness after treatment with supramolecular self-gelling powder.

[0072] Figure 30 This is a Masson staining result of wound tissue after treatment with supramolecular self-gelling powder.

[0073] Figure 31 The images show the results of wound thickness and collagen deposition rate after treatment with supramolecular self-gel powder. In the image, a is the result of wound thickness analysis by Masson staining, and b is the result of collagen deposition rate analysis by Masson staining.

[0074] Figure 32 Immunohistochemical staining results of Col I and Col III in wound tissue after treatment with supramolecular self-gelling powder.

[0075] Figure 33 The images show the content and ratio of Col I and Col III collagen in the wound tissue after treatment with supramolecular self-gel powder. In the images, a represents the content of type I collagen (Col I), b represents the content of type III collagen (Col III), and c represents the ratio of type I collagen content to type III collagen content.

[0076] Figure 34 The images show the expression results of inflammatory iNOS protein and anti-Arg protein in wound tissue after treatment with supramolecular self-gel powder. In the images, a is the immunofluorescence staining image of inflammatory iNOS protein and Arg1 protein, b is the Arg1 content image, and c is the iNOS content image.

[0077] Figure 35 The images show the expression results of inflammatory cytokines IL6 and IL10 in wound tissue after treatment with supramolecular self-gel powder. In the images, a represents the IL-6 content and b represents the IL-10 content.

[0078] Figure 36 This image shows the immunofluorescence staining results of wound tissue after treatment with supramolecular self-gel powder.

[0079] Figure 37 This is a graph showing the relative number of blood vessels in the wound tissue after treatment with supramolecular self-gel powder. Detailed Implementation

[0080] The following non-limiting embodiments are intended to enable those skilled in the art to more fully understand the invention, but do not limit the invention in any way.

[0081] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; the reagents and materials described are commercially available unless otherwise specified.

[0082] Example 1

[0083] A method for preparing a piezoelectric antibacterial supramolecular self-gelling hemostatic powder (DP3NB) includes the following steps:

[0084] (1) Preparation of nano-clay suspension: 0.2 g Laponite XLS was added to 1 mL of deionized water and ultrasonically dispersed for 10 min to obtain a uniform aqueous suspension;

[0085] (2) Preparation of mixed solution: Under stirring at 500 rpm, 2.5 g DMAPS, 0.25 g PAA and 2 mg BTO were added to the above suspension in sequence, and stirred for 10 min until the components were fully mixed to obtain a mixed solution;

[0086] (3) Polymerization and drying: The mixed solution was poured into a silicone mold and polymerized at 60℃ for 45 min to form a supramolecular hydrogel (DPNB hydrogel). After drying in an oven at 60℃ for 24 h, it was ground by ball mill (ball-to-material ratio 10:1, speed 300 rpm, grinding for 2 h) to obtain powder, which was named DP3NB.

[0087] Example 2

[0088] The difference between this embodiment and embodiment 1 is that in step (2), DMAPS is 2.5 g, PAA is 0.15 g, BTO is 2 mg, and the final powder is named DP1NB.

[0089] Example 3

[0090] The difference between this embodiment and embodiment 1 is that in step (2), DMAPS is 2.5 g, PAA is 0.2 g, BTO is 2 mg, and the final powder is named DP2NB.

[0091] Example 4

[0092] The difference between this embodiment and embodiment 1 is that in step (2), DMAPS is 2.5 g, PAA is 0.3 g, BTO is 2 mg, and the final powder is named DP4NB.

[0093] The structure of the supramolecular hydrogel and hemostatic powder DP3NB obtained in Example 1 was tested, and the results are shown in the figure. Figure 1 :

[0094] from Figure 1 As can be seen from a, when phosphate buffer (PBS) is added to DPNB powder of different shapes, the powder will rapidly expand on its own to form a physically cross-linked, shape-adaptive supramolecular hydrogel without any additional complex preparation steps.

[0095] To further investigate the self-gelling effect of DPNB powder, the process of the powder contacting PBS solution and transforming into a supramolecular hydrogel was observed under a microscope. The results are shown in [Figure number missing]. Figure 1 b. It can be seen that the DPNB powder quickly absorbs water, expands and connects with each other, forming a blocky hydrogel within about 3 seconds.

[0096] The gelation time of DPNB powder was determined by time-scan rheological testing, and the results are shown in the figure. Figure 1 c. It can be seen that the storage modulus (G') curve intersects with the loss modulus (G'') curve at approximately 3 seconds, indicating that the powder can complete the transformation into a hydrogel within 3 seconds, demonstrating its potential for rapid sealing of bleeding points. Furthermore, frequency-scanning rheological tests show that the storage modulus (G') is significantly greater than the loss modulus (G''), and the storage modulus does not change with frequency. Figure 1 (d) This indicates that the DPNB hydrogel has typical elastic behavior and solid-state properties, further confirming that the stable hydrogel network is formed only through physical interactions.

[0097] Fourier transform infrared (FTIR) spectroscopy further revealed the crosslinking mechanism of the DPNB hydrogel, and the results are shown in [Figure number missing]. Figure 1 e, it can be seen that: 1635 cm in PAA -1 The carboxyl (-COOH) peak at 3480 cm⁻¹ and DMAPS -1 The amino (-NH2 or -NH) peaks at the 100°C and 100°C peaks at the DPNB were shifted to 1710 cm⁻¹, respectively. -1 and 3450 cm -1 The shifts in these absorption peaks reflect changes in intermolecular interactions, confirming the existence of hydrogen bonds and electrostatic interactions. However, the absence of new characteristic peaks further confirms that the DPNB hydrogel is cross-linked through supramolecular interactions rather than covalent bonds.

[0098] The adhesion properties of the supramolecular hydrogels obtained in Examples 1-4 were tested, and the results are shown in the figure. Figure 2 and Figure 3 :

[0099] The shear strength of the hydrogel and pig skin was determined by shear test, and the maximum pressure at which the powder seal on a 2 mm hole in the pig skin failed was determined by burst pressure test.

[0100] Results analysis: Figure 2 The hydrogel obtained in Example 1 exhibited good adhesion, with a shear adhesion strength of 112 kPa. Its adhesion increased with increasing PAA content. Therefore, Example 1 was significantly higher than Example 2 (60 kPa) and Example 3 (70 kPa), but lower than Example 4 (140 kPa), because PAA can form strong hydrogen bonds with the amine groups on the tissue surface through carboxyl groups. Figure 3 The hydrogel obtained in Example 1 exhibits a burst pressure of 285 mmHg, significantly higher than that of Examples 2 (90 mmHg), 3 (120 mmHg), and 4 (160 mmHg). Excessive PAA leads to a decrease in burst pressure performance and weakens sealing ability. In summary, the hydrogel obtained in Example 1 (DP3NB) exhibits the best adhesion performance.

[0101] Example 5

[0102] The difference between this embodiment and embodiment 1 is that in step (1), 0.1 g of Laponite XLS is added to 1 mL of deionized water, and the resulting powder is named DPN1B.

[0103] Example 6

[0104] The difference between this embodiment and embodiment 1 is that in step (1), 0.3 g of Laponite XLS is added to 1 mL of deionized water, and the resulting powder is named DPN3B.

[0105] The hemostatic powders obtained in Examples 1, 5, and 6 were subjected to coagulation performance tests, and the results are shown in the figure. Figures 4-6 :

[0106] The powder was mixed with whole blood, and the time to form a stable clot was recorded. Red blood cell (RBC) aggregation on the powder surface was observed using SEM, and the RBC adhesion rate was calculated. The test without any powder was used as a control group, with whole blood directly placed in the same environment for testing. This was used to obtain baseline clotting time and RBC natural state data, serving as a baseline for performance comparison. The powder obtained without PAA was named DP0NB powder (all other operations were the same as in Example 1); the powder obtained without nano-clay was named DPN0B powder (all other operations were the same as in Example 1).

[0107] Results Analysis: The in vitro coagulation ability of DPNB powder was assessed by measuring the clotting time after mixing with whole blood. Results are shown below. Figure 4It can be seen that the clotting time of the blank group was approximately 7 minutes. Both DP0NB and DPN0B groups exhibited certain procoagulant abilities, forming stable clots within 60 s and 300 s, respectively. The results indicate that both the adhesiveness of PAA and the coagulability of XLS can accelerate clot formation, with XLS showing a more significant effect. Therefore, the coagulant ability of DPNB powder with different concentrations of XLS was investigated. With increasing XLS content, the clotting time of DPNB powder significantly decreased to approximately 20 s. The clotting time of the DPN3B group increased again, possibly because excessive cross-linking of the nanoclay affected the polymerization of the DPNB powder, weakening its coagulant properties. Red blood cell (RBC) adhesion and aggregation play a crucial role in blood coagulation and hemostasis. The morphology of adhered RBCs was characterized by obtaining scanning electron microscopy images, and the results are shown in [Figure 1]. Figure 5 and Figure 6 It can be seen that a large number of RBCs are attached to the DPNB powder, and DP3NB exhibits larger and denser RBC aggregation. Figure 5 Meanwhile, the erythrocyte adhesion assay further showed that the DP3NB group had the highest erythrocyte adhesion rate, reaching 90.4%. Figure 6 Therefore, DP3NB powder exhibits the best in vitro hemostatic properties.

[0108] The hemostatic powder DP3NB obtained in Example 1 was subjected to an in vivo hemostatic test, and the results are shown in the figure. Figures 7-9 :

[0109] Rat models of partial hepatectomy (removal of liver lobe), femoral artery puncture (femoral artery puncture), and tail vein transection (tail vein transection) were established. Powder was uniformly applied to the wound surface of each model, and hemostasis time and blood loss were recorded. The test without any powder was used as a control group to obtain data on hemostasis time and blood loss, serving as a baseline for performance comparison. Commercially available chitosan powder was used as a control group.

[0110] Results Analysis: The in vivo hemostatic properties of DPNB powder were verified in a rat model of incompressible liver hemorrhage. Results are shown below. Figure 7 As can be seen, in the rat partial hepatectomy model with incision, the untreated control group experienced severe bleeding, with a maximum blood loss of 902 mg and a hemostasis time of up to 317 s. After applying traditional hemostatic materials chitosan and DPNB powder to the wound site, the blood loss (412 mg and 224 mg, respectively) and hemostasis time (197 s and 40 s, respectively) in both groups were reduced. Large vessel injury is often accompanied by rapid pressurized blood flow and fatal bleeding. The hemostatic ability of DPNB powder was further verified using a rat femoral artery hemorrhage model, and the results are shown in […]. Figure 8It can be seen that after femoral artery puncture, traditional chitosan failed to stop arterial bleeding, while DPNB powder rapidly absorbed blood and formed a strong sealing layer, achieving hemostasis within 20 seconds, and no secondary bleeding occurred during the observation period; compared with the control group, the blood loss in the DPNB group was reduced by 70%. The same trend was observed in a mouse tail amputation model, as shown in the results below. Figure 9 The results show that chitosan failed to stop tail bleeding, while DPNB powder rapidly stopped bleeding within 45 seconds, with a significantly smaller hemostatic volume compared to the control group. These results indicate that DPNB hydrogel can withstand the pressure of arterial rupture and has the ability to stop bleeding in high-pressure arteries. In conclusion, DP3NB powder exhibits the best in vivo hemostatic performance.

[0111] The piezoelectric catalytic performance of the hemostatic powder DP3NB obtained in Example 1 was tested, and the results are shown in [the table below]. Figures 10-12 :

[0112] The powder was dispersed in PBS at a concentration of 0.3–1.2 W / cm². 2 Irradiated under ultrasound for 10 min, and then a TA probe (reacting with •OH to generate fluorescent HTA) and a SOSG probe (reacting with •OH to generate fluorescent HTA) were used. 1 O2 reaction generates fluorescent products), and the •OH and •OH are measured by a fluorescence spectrophotometer. 1 The amount of O2 generated. The test without adding any powder was used as a blank group (Control) as the baseline for comparing piezoelectric catalytic performance; the powder obtained without adding BTO was named DPN powder.

[0113] Results Analysis: The generation of ROS was confirmed by electron spin resonance (ESR) measurements, as shown in the table below. Figure 10 5,5-Dimethyl-1-pyrrolidone-N-oxide (DMPO) and 2,2,6,6-tetramethyl-4-piperidinone (TEMP) were used as •OH and 1 The spin-trapping mixture of O2 showed that DMPO-OH exhibited a typical 1:2:2:1 quartet signal and TEMPONE a 1:1:1 triplet signal. The piezoelectric catalytic ability of DPNB powder to generate ROS under ultrasonic stimulation is shown in the results. Figure 11The production of hydroxyl radicals (•OH) was measured using phthalic acid (TA). TA, acting as a probe molecule, reacts with •OH to generate fluorescent 2-hydroxyterephthalic acid (HTA). It was observed that as the irradiation time of DPNB powder under ultrasonic stimulation increased from 0 min to 10 min, the fluorescence intensity of HTA at 426 nm gradually increased; particularly at 10 min of ultrasonic stimulation, the fluorescence intensity was 3.5 times that at 1 min, indicating that the generation of •OH is time-dependent. Furthermore, under the same ultrasonic stimulation conditions, DPNB produced more •OH than DPN, confirming the importance of BTO in the piezoelectric catalytic effect of self-gelling powder formation. In addition, the commercial ROS fluorescent probe singlet oxygen sensor green (SOSG) was used to measure singlet oxygen (…). 1 The generation of O2. Under ultrasonic stimulation, DPNB powder exhibits better performance than DPN. 1 The O2 generation capacity was observed, and the fluorescence intensity of SOSG at 540 nm gradually increased with increasing ultrasound duration. Ultrasound intensity significantly affected ROS generation; results are shown in [Figure number missing]. Figure 12 It can be seen that when the ultrasonic power increases from 0.3 W / cm 2 Increased to 1.2 W / cm 2 At that time, the •OH ( ) measured by the above method Figure 12 a) and 1 O2 ( Figure 12 (b) Both increased significantly, indicating that the ROS content can be controlled by the ultrasonic intensity. In summary, this confirms that DPNB powder has excellent piezoelectric catalytic ability to generate ROS under ultrasonic conditions.

[0114] The antibacterial properties of the hemostatic powder DP3NB obtained in Example 1 were tested, and the results are shown in the figure. Figures 13-16 :

[0115] After co-culturing Escherichia coli and Staphylococcus aureus suspensions with powder for 1 h, respectively, the cultures were subjected to a microenvironmental stimulation (MES) of 0.3–1.2 W / cm². 2 The sterilization rate was calculated by agar plate colony counting method after 10 min of ultrasonic (US) irradiation or without ultrasonication. The test without any powder was used as the blank group (Control) as the baseline for antibacterial performance comparison; the test without any powder and the test with only ultrasonication (Control+US) was used as the baseline for ultrasonic antibacterial performance comparison; the powder obtained without BTO was named DPN powder.

[0116] Results analysis: From Figure 13 and Figure 14It can be seen that compared with the unirradiated group, the survival rate of Escherichia coli and Staphylococcus aureus in the US-irradiated group decreased; the Control+US group and DPN+US group showed weaker bactericidal ability, the potential mechanism of which may be the mechanical damage and cavitation effect of US; the DPNB+US group showed a strong bactericidal effect, with the number of bacterial colonies on agar plates decreasing to about 5% after 10 min of US stimulation. The antibacterial effect of DPNB powder was also specifically verified by colony forming unit (CFU) counting method. For Escherichia coli, the bactericidal rates of the Control group, DPN group, DPNB group, Control+US group, DPN+US group, and DPNB+US group were approximately 5.8%, 19.1%, 40.3%, 43.2%, and 94.1%, respectively. For Staphylococcus aureus, the bactericidal rates of the Control group, DPN group, DPNB group, Control+US group, DPN+US group, and DPNB+US group were approximately 2.7%, 7.9%, 48.3%, 55.4%, and 94.9%, respectively. The results showed that the ROS generated by DPNB powder under the action of US significantly improved the antibacterial effect. Figure 15 and Figure 16 It can be seen that as the ultrasound power increases, under the same irradiation time (10 min), the bacterial colony gradually decreases, exhibiting an ultrasound intensity-dependent bactericidal effect. When the power increases from 0.3 W / cm², the bacterial colony gradually decreases. 2 Increased to 1.2 W / cm 2 At this time, the bactericidal efficiency against Escherichia coli increased from 40.7% to 91.9%, and the bactericidal efficiency against Staphylococcus aureus increased from 51.9% to 93.3%. This is because increasing the ultrasonic power stimulates DPNB to generate more ROS. ROS destroys the permeability of the bacterial membrane through the peroxidation of polyunsaturated phospholipids in the lipid membrane, leading to bacterial death. This verifies the excellent effect of DPNB powder in improving antibacterial performance by generating ROS after increasing the ultrasonic strength. When the ultrasonic power reaches 0.9 W / cm², the bactericidal efficiency against Escherichia coli increased from 40.7% to 91.9%, and the bactericidal efficiency against Staphylococcus aureus increased from 51.9% to 93.3%. 2 Satisfactory antibacterial effects were achieved, with bactericidal rates of 83.8% and 85.1% against Escherichia coli and Staphylococcus aureus, respectively. In summary, the DPNB+US group showed ideal bactericidal rates, confirming the excellent in vivo antibacterial effect of DPNB powder under high-power ultrasound.

[0117] Cell proliferation and migration tests were performed on the hemostatic powder DP3NB obtained in Example 1. The results are shown in [Figure 1]. Figures 17-24 :

[0118] (1) Cell proliferation test: L929 cells were co-cultured with powder extract, and the OD of cells at 1 day, 3 days and 5 days was detected by CCK-8 assay. 450 Value (reflecting cell number); after co-culture, 0.3 W / cm² was used.2 Compare the differences in proliferation between ultrasound irradiation for 10 minutes / day and no ultrasound.

[0119] (2) Cell migration test: A scratch assay was used to create scratches in a cell monolayer, and powder extract was added; 0.3~1.2 W / cm² was used. 2 Scratch closure rates were recorded at 0 h, 12 h, and 24 h after 10 min of ultrasonic irradiation or without ultrasonic treatment.

[0120] The test of culturing L929 cells with cell culture medium without adding any powder was used as the blank group; the test of culturing L929 cells with cell culture medium without adding any powder and combining it with ultrasound was named Control+US; the powder obtained without adding BTO was named DPN powder.

[0121] Results Analysis: The effect of the piezoelectric effect of DPNB powder under US irradiation on fibroblast proliferation was studied. The results are shown in […]. Figure 17 and Figure 18 It can be seen that: fibroblasts were cultured together with DPN and DPNB powder for 24 hours, and then treated with 0.3 W / cm 2 Ultrasonic irradiation was used as a control group to compare cell growth effects with the untreated group. The results showed that the cell proliferation effect in the US irradiation group was significantly more pronounced. Specifically, after 5 days of culture, the relative cell numbers in the Control, DPN, DPNB, Control+US, DPN+US, and DPNB+US groups were 569, 673, 736, 913, 930, and 1138, respectively. It can be seen that the cell number in the DPNB+US group was much higher than that in the DPNB group, indicating that DPNB powder can promote cell proliferation under the piezoelectric effect generated by ultrasound. The cell proliferation effect was also related to the ultrasound power, as shown in the results below. Figure 19 and Figure 20 It can be seen that when the ultrasonic power is 0.3 W / cm 2 The cell proliferation effect was best at this stage, reaching 894 cells on day 5; as the ultrasound power continued to increase, the cell proliferation rate began to slow down, with a peak at 0.6 W / cm². 2 and 0.9 W / cm 2 On day 5, the proliferation rates reached 820 and 722 respectively, still better than the control group; when the ultrasound power increased to 1.2 W / cm²... 2 In contrast, the cell proliferation rate was lower in the control group. This indicates that high-intensity ultrasound may cause cell damage and death due to excessive ROS and strong mechanical vibration effects. In summary, this confirms that DPNB powder promotes cell proliferation under low-intensity ultrasound.

[0122] The migration of fibroblasts cultured in DPNB powder was assessed using a scratch assay. Results are shown in [Figure number missing]. Figure 21 and Figure 22 As can be seen, the DPNB+US group exhibited the fastest scratch closure speed and the smallest cell gap area (7.5%) after 24 hours of culture. In contrast, the cell gap areas of the Control group, DPN group, DPNB group, Control+US group, and DPN+US group were 25.8%, 17.4%, 16.9%, 12.4%, and 10.1%, respectively. This may be because DPNB generates appropriate concentrations of ROS and piezoelectric effects under ultrasound, which can adjust the local cytoskeleton at the molecular level and promote fibroblast migration by activating redox signaling cascades. Therefore, this also provides a strong contractile force for wound healing in the epidermis and subcutaneous tissues. The effect of different ultrasound powers on fibroblast migration was observed, and the results are shown in [Figure 1]. Figure 23 and Figure 24 It can be seen that at 0.3 W / cm 2 At the highest power, cell migration was most significant, with a cell gap area of ​​6.8% after 24 hours; at 0.6 W / cm², cell migration was most pronounced. 2 and 0.9 W / cm 2 Significant cell migration was also observed, but the migration rate was significantly reduced, at 10.9% and 21.6%, respectively; at 1.2 W / cm²... 2 Cell migration efficiency (24.7%) initially decreased to less than 0 W / cm². 2 (22.6%), which may be due to cell damage caused by excessive ultrasound intensity, thus interfering with cell migration. In summary, this study reveals the potential application value of DPNB powder under ultrasound to accelerate cell migration and promote wound healing.

[0123] Example 7

[0124] The supramolecular self-gel powder DP3NB obtained in Example 1 was used in combination with spatiotemporal acoustic dynamics to achieve antibacterial healing. The results are shown in […]. Figures 25-27 :

[0125] Establish a rat dorsal full-thickness infected wound model (1 cm in diameter, inoculated with 1×10⁻⁶ cells / year). 5 CFU (Staphylococcus aureus); apply powder to the wound surface, do not use ultrasound, or use spatiotemporal sonodynamic modulation treatment: 0-3 days with 0.9 W / cm 2 Ultrasonic irradiation for 10 minutes / day (antibacterial phase), 0.3 W / cm² for 4-14 days. 2Ultrasonic irradiation was performed for 10 minutes per day (healing promotion phase); the wound closure rate was recorded after 14 days of observation. The control group (without any powder) served as the baseline for comparing wound healing performance; the control+US group (without any powder, only ultrasound) served as the baseline for comparing ultrasonic wound healing performance; the powder obtained without BTO was named DPN powder.

[0126] Results analysis: From Figures 25-27 It can be seen that in the first half of the treatment, from day 0 to day 3, high-intensity US (0.9 W / cm²) was used. 2 Antibacterial treatment was administered. The DPNB+US group showed less exudate around the wound and the best tendency to close, while the Control and Control+US groups had poorer wound environments, with noticeable deepening and extensive scab formation. The DPN and DPN+US groups showed weaker healing effects, possibly related to providing a moist environment conducive to wound healing. The DPNB+US group also achieved the best wound area closure rate of 45.5% on day 3, confirming the effectiveness of high-intensity US (0.9 W / cm²). 2 While sterilizing, it also promotes wound healing. The wound area closure rates on day 3 for the Control group, DPN group, DPNB group, Control+US group, and DPN+US group were 4.8%, 17.0%, 31.1%, 14.2%, and 33.6%, respectively. This indicates that both DPN powder and ultrasound therapy have a certain healing effect on infected wounds, with the DPNB+US group, which has a piezoelectric effect, showing the best healing effect. Simultaneously, in the latter half of the treatment, from day 3 to 14, low-intensity ultrasound (0.3 W / cm²) was used. 2 Accelerating wound healing. On day 14, the wound area closure rates of the Control group, DPN group, DPNB group, Control+US group, DPN+US group, and DPNB+US group were 47.7%, 68.9%, 91.8%, 57.5%, 72.5%, and 96.3%, respectively. It can be seen that the DPNB+US group had the fastest wound healing speed, with the wound almost completely disappearing on day 14, confirming that the piezoelectric effect generated by DPNB powder under low-intensity ultrasound is beneficial to rapid cell proliferation and migration. In summary, this segmented sonodynamic therapy, which utilizes high-intensity ultrasound to eliminate bacteria and low-intensity ultrasound to accelerate healing, can reduce tissue damage, balance antibacterial activity and cell vitality, and optimize the healing effect of infected wounds.

[0127] Wound tissue from Example 7 was collected and subjected to histological testing. The results are shown in [the table below]. Figures 28-37 :

[0128] H&E staining: to observe epidermal thickness, continuity, and inflammatory cell infiltration; Masson staining: to analyze collagen deposition and orientation; immunohistochemical staining: to detect the content and ratio of type I collagen (Col I) and type III collagen (Col III); immunofluorescence staining: to label vascular smooth muscle actin (α-SMA) and quantify the number of new blood vessels.

[0129] Results analysis:

[0130] H&E staining results are shown in […]. Figure 28 and Figure 29 As can be seen, the wounds in the DPNB+US group had a thicker average epidermal thickness (99.7 μm), with a more continuous and layered epidermal layer, resembling normal skin. Neutrophils and lymphocytes were less common in the subcutaneous tissue, while the control group still showed more inflammatory infiltration and tissue debris. This indicates that DPNB powder, with its ideal bactericidal ability, can improve the wound healing microenvironment. Furthermore, the tissue regeneration in the ultrasound or DPN powder treatment groups was superior to that in the control group, demonstrating that the hydrogel's inherent healing properties and the mechanical stimulation of ultrasound can accelerate skin regeneration and wound recovery.

[0131] During wound healing, relatively high-density collagen helps increase the elasticity of regenerated tissue, thereby maintaining the physical continuity between existing and newly formed skin tissue. Masson staining was used to assess collagen distribution at the wound site; the results are shown below. Figure 30 and Figure 31 As a component of the skin, collagen synthesis, deposition, and orientation play a crucial role in wound repair, and the presence of collagen deposition is beneficial to the healing process. Clearly, the DPNB+US group had more deposited and highly oriented collagen structures (67.2%), exhibiting better extracellular matrix remodeling and epithelial tissue reconstruction.

[0132] Col I and Col III are important collagen types in connective tissue and play a key role in different stages of wound healing. Immunohistochemical staining was used to further explore the mechanism by which DPNB powder promotes wound healing. Results are shown below. Figure 32 and Figure 33 The results show that the Col I and Col III collagen levels in the DPNB+US group were 1.7 times and 2.3 times higher than those in the Control group, respectively. Notably, the ratio of type I to type III collagen was lower in the ultrasound treatment groups, while the DPNB+US group had the lowest ratio. This indicates that DPNB powder not only promotes collagen deposition and accelerates healing but also amplifies ultrasound treatment to reduce scar tissue formation, thus facilitating collagen network remodeling.

[0133] To evaluate the inflammatory regulatory effect of the powder on wound tissue, immunofluorescence staining was used to detect the macrophage phenotype in each group. M1 and M2 macrophages were labeled with inducible nitric oxide synthase (INOS) and arginase 1 (ARG1), respectively. Results are shown below. Figure 34 and Figure 35 It can be seen that, compared with the Control group, the DPNB+US group significantly reduced the expression of inflammatory iNOS protein and increased the secretion of anti-inflammatory Arg1 protein. ELISA detection also demonstrated that the DPNB+US group had the lowest inflammatory cytokine IL6 and the highest IL10 in skin tissue, both indicating that DPNB powder combined with ultrasound can effectively reduce local inflammation, regulate the transformation of macrophages to the anti-inflammatory M2 phenotype, and promote wound repair. Furthermore, angiogenesis is a key step in wound healing because it helps provide oxygen and nutrients, remove metabolic waste, support cell migration and proliferation, and promote granulation tissue formation. Therefore, immunofluorescence staining was performed on angiogenesis markers (α-SMA), and the results are shown below. Figure 36 and Figure 37 It can be seen that the relative number of blood vessels in the US group was greater than that in the group without US, indicating that ultrasound promotes angiogenesis. The DPNB+US group had the highest relative number of blood vessels, which was 5.7 times that of the Control group, indicating that DPNB powder combined with ultrasound can greatly accelerate the growth of new capillaries entering the wound.

[0134] In summary, this invention develops a piezoelectric antibacterial supramolecular self-gelling hemostatic powder. This powder can rapidly stop bleeding in irregularly shaped wounds and can serve as an effective wound dressing, exerting a comprehensive therapeutic effect when combined with sonodynamic optimization technology. Upon contact with blood, the DPNB powder rapidly forms a highly adhesive hydrogel through physical cross-linking. Furthermore, in various rat bleeding wound models, the DPNB powder can promote hematopoietic cell aggregation and achieve effective hemostasis. Notably, by using spatiotemporal sonodynamically regulated antibacterial healing technology to control the reactive oxygen species (ROS) generated by the piezoelectric catalysis of the DPNB powder, the healing protocol for infected wounds is further optimized. Specifically, during the first 0-3 days of treatment, high-intensity ultrasound is used to clear wound bacteria; from day 3 to day 14, low-intensity ultrasound is used to further promote cell proliferation and migration, effectively clearing wound bacteria, accelerating the inflammatory process, stimulating collagen deposition, enhancing epidermal regeneration and angiogenesis, thereby reducing scar formation, achieving excellent wound repair effects, and ultimately improving healing efficiency. The novel self-gelling supramolecular hemostatic powder combined with ROS regulation technology provided by this invention offers a new approach to healing refractory wounds, and has significant scientific value and broad clinical application prospects.

Claims

1. Piezoelectric antibacterial supramolecular self-gelling hemostatic powder, characterized in that: The self-gelling hemostatic powder is obtained by drying and grinding a hydrogel, wherein, The hydrogel is formed by uniformly dispersing nano-clay and piezoelectric nanoparticles in a network structure of zwitterionic polymer and polyacrylic acid through supramolecular interactions. The zwitterionic polymer is [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide.

2. The hemostatic powder according to claim 1, characterized in that: The nano-clay is Laponite XLS; the piezoelectric nanoparticles are barium titanate.

3. The hemostatic powder of claim 1, wherein: The supramolecular interactions are one or both of hydrogen bond or electrostatic interaction.

4. The hemostatic powder of claim 1, wherein: The hydrogel is prepared by a polymerization reaction of nano-clay, zwitterionic polymer, polyacrylic acid, piezoelectric nanoparticles and deionized water, wherein the mass ratio of the nano-clay, zwitterionic polymer, polyacrylic acid and piezoelectric nanoparticles is 1-3 : 25 : 1.5-3 : 0.015-0.025, and the mass-volume ratio of the nano-clay and deionized water is 1-3 g : 10 mL.

5. Process for the preparation of the haemostatic powder according to any one of claims 1 to 4, characterized in that: The zwitterionic polymer, polyacrylic acid and piezoelectric nanoparticles are sequentially added to the nano-clay suspension under stirring, and then the polymerization reaction is carried out after stirring and mixing, followed by drying and grinding to obtain the hemostatic powder.

6. The method of claim 5, wherein: The polymerization reaction condition is 60℃ for 45 min.

7. The method of claim 5, wherein: The stirring rate is 500 rpm, and the stirring and mixing time is 10 min.

8. The method of claim 5, wherein: The drying condition is 60℃ for 24 h in an oven.

9. The method of claim 5, wherein: The grinding is carried out by a ball mill with a ball-to-material ratio of 10:1 at a speed of 300 rpm for 2 h.

10. Use of the hemostatic powder of any one of claims 1-4 or prepared by the method of any one of claims 5-9 in the preparation of a material for treating acute bleeding and / or wound healing.

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