Ultrasonic response piezoelectric hydrogel material as well as preparation method and application thereof
By preparing an ultrasonically responsive piezoelectric hydrogel material composed of polyvinyl alcohol, sodium alginate, anhydrous calcium chloride, dopamine-modified barium titanate, and cerium-doped carbon dots, the problems of limited functionality in traditional wound dressings and poor flexibility of piezoelectric materials were solved, achieving efficient wound healing and pain relief effects.
Patent Information
- Application Number
- CN202511317545.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-16
- Publication Date
- 2025-12-19
AI Technical Summary
Existing wound dressings have limited functionality. Traditional piezoelectric materials are complex to prepare, costly, and lack flexibility, making them difficult to fit irregular wounds. Furthermore, their piezoelectric response strength and biocompatibility are insufficient.
An ultrasonically responsive piezoelectric hydrogel material composed of polyvinyl alcohol, sodium alginate, anhydrous calcium chloride, dopamine-modified barium titanate, and cerium-doped carbon dots is formed through freeze-thaw cycles to create a piezoelectric network, generating microcurrents to promote wound healing, while also incorporating the moisturizing properties of the hydrogel.
It generates a stable microcurrent under low-intensity ultrasound stimulation, which enhances fibroblast migration, angiogenesis and epithelial regeneration, reduces pain, and has antioxidant, anti-inflammatory and antibacterial capabilities, enabling rapid hemostasis and exudate management, and promoting wound healing.
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Figure CN121154901A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of wound repair materials, in particular to a high ultrasonic response piezoelectric hydrogel material, a preparation method thereof and application thereof in promoting wound healing. BACKGROUND
[0002] Skin, as the outermost protective barrier of the human body, once damaged, will seriously affect the body's defense function. Traditional wound dressings such as gauze, ordinary hydrogel or film materials have single function and only have basic covering and protection function, and have many shortcomings. For example, gauze has limited liquid absorption capacity, is easy to adhere to the wound surface, and causes secondary damage when dressing is changed; traditional piezoelectric materials are sensitive to environmental conditions, and have complex preparation process, high cost, hard and brittle texture and poor flexibility, which makes it difficult to fit irregular wounds, limiting its application in flexible wound repair.
[0003] In recent years, flexible piezoelectric hydrogel dressings have become a research hotspot because they have piezoelectric response and hydrogel flexibility. The material not only can fit complex wounds, but also can generate micro-current when stimulated by external stimuli (such as ultrasound), promote cell migration and angiogenesis, and accelerate tissue repair. However, the existing materials still need to be improved in terms of piezoelectric response strength, biocompatibility and preparation process. SUMMARY
[0004] The purpose of the present application is to solve the problems in the prior art, and to provide an ultrasonic response piezoelectric hydrogel material, a preparation method thereof and application thereof.
[0005] The present application ingeniously combines the piezoelectric effect and the moisturizing performance of the hydrogel, achieving a synergistic effect of complementing each other. When external pressure is applied to the hydrogel, it can generate a relatively weak electric current, and this piezoelectric effect has a good promoting effect on blood circulation and cell activity at the wound site, thereby accelerating the healing speed of the wound. Moreover, the piezoelectric effect can stimulate the nerve endings around the wound, so that the patient's pain is reduced. At the same time, the water absorption and water retention ability of the hydrogel itself creates a moist healing environment for the wound, promotes epithelial cell regeneration and promotes wound healing.
[0006] In order to achieve the above purpose, the present application is realized by the following technical scheme:
[0007] In a first aspect, the present application provides an ultrasonic response piezoelectric hydrogel material, which is composed of polyvinyl alcohol, sodium alginate, anhydrous calcium chloride, dopamine-modified barium titanate and cerium-doped carbon dots, and forms a piezoelectric network through freeze-thaw cycles to generate a micro-current under ultrasonic stimulation to promote wound healing.
[0008] Preferably, the mass ratio of polyvinyl alcohol, sodium alginate, anhydrous calcium chloride, dopamine modified barium titanate and cerium doped carbon dots is 80:20:20:20:1.
[0009] In a second aspect, the present application provides a preparation method of the ultrasonic response piezoelectric hydrogel material, which comprises the following steps:
[0010] Step 1, polyvinyl alcohol and deionized water are placed in a beaker and heated and stirred, and then dopamine modified barium titanate and cerium doped carbon dots are sequentially added and fully stirred and mixed uniformly;
[0011] Step 2, after cooling, anhydrous calcium chloride is added to the beaker, and after fully stirring and mixing uniformly, sodium alginate is slowly added and stirred, and then the solution is ultrasonically treated after the sodium alginate is completely dissolved in the solution;
[0012] Step 3, the mixed solution obtained in step 2 is poured into a culture dish, and freeze-thaw cycle is performed, thereby obtaining the piezoelectric hydrogel material.
[0013] Preferably, in step 1, the mass ratio of polyvinyl alcohol, dopamine modified barium titanate and Ce carbon dots is 80:20:1; the heating and stirring condition is 90℃ oil bath, and the stirring time is 3h.
[0014] Preferably, in step 1, the preparation method of dopamine modified barium titanate is as follows:
[0015] BTO powder, Tris Base powder and deionized water are uniformly mixed under ultrasonic to obtain a suspension; then dopamine hydrochloride is added to the suspension and stirred to obtain a dopamine modified barium titanate aqueous solution; subsequently, the solution is centrifuged by a high-speed centrifuge, and the centrifuged liquid is dried to obtain dopamine modified barium titanate, wherein the mass ratio of BTO powder, Tris Base powder and dopamine hydrochloride is 2:0.49:3.6.
[0016] Preferably, in step 1, the preparation method of cerium doped carbon dots is as follows:
[0017] Anhydrous citric acid and deionized water are mixed and stirred uniformly; then cerium nitrate hexahydrate and p-phenylenediamine are added respectively, and after stirring uniformly, heating reaction is performed; the obtained solution is subjected to suction filtration, dialysis and freeze-drying to obtain cerium doped carbon dots, wherein the mass ratio of cerium nitrate hexahydrate, anhydrous citric acid and p-phenylenediamine is 2.4:3.186:2.994.
[0018] Preferably, the heating reaction condition is 180℃ for 6h.
[0019] Preferably, in step S2, the mass ratio of polyvinyl alcohol, anhydrous calcium chloride and sodium alginate is 4:1:1, and the temperature after cooling is 60℃.
[0020] Preferably, in step 3, the freezing and thawing condition is that the sample is put into a freezing environment at-18 DEG C for 8 hours and then thawed at room temperature for 2 hours.
[0021] In a third aspect, the application provides the use of the material in a medical dressing for promoting wound healing.
[0022] The application has the following beneficial effects: the application successfully achieves the synergistic effect of the piezoelectric effect and the moisturizing property of the hydrogel by introducing the dopamine-modified barium titanate and the Ce-containing carbon dots to construct a high interface polarization structure, so that stable micro-current can be generated under low-intensity ultrasonic stimulation, and the regulation and control capability on fibroblast migration, angiogenesis and epithelial regeneration is significantly enhanced; in addition, the piezoelectric effect also has the effect of stimulating nerve endings around the wound, which helps to reduce the pain felt by the patient. The ultrasonic response performance is better than that of the traditional PVA-based piezoelectric hydrogel, the electric signal intensity is increased by 2-3 times, and non-invasive and remotely controllable bioelectric stimulation treatment is realized.
[0023] The piezoelectric hydrogel material prepared by the application has multiple biological activity synergies, and the material has antioxidant, anti-inflammatory and antibacterial properties; the cell adhesion and tissue integration capability is enhanced; at the same time, the ion cross-linking network formed by sodium alginate and calcium ions has the capability of rapid hemostasis and exudate management.
[0024] The piezoelectric hydrogel prepared by the application has the capability of maintaining a moist state for a long time, which can effectively avoid the problems of cracking and infection caused by dry wound, and through animal model experiments, it can be seen that the piezoelectric hydrogel prepared by the application exhibits more excellent wound healing capability, and has good application prospect. BRIEF DESCRIPTION OF DRAWINGS
[0025] Figure 1 SEM picture of the ultrasonic response piezoelectric hydrogel material (10 mu m);
[0026] Figure 2 SEM picture of the ultrasonic response piezoelectric hydrogel material (5 mu m);
[0027] Figure 3 TEM diagram of Ce-CDs;
[0028] Figure 4 XPS diagram of Ce-CDs;
[0029] Figure 5 TEM diagram of dopamine-modified barium titanate (PBT);
[0030] Figure 6 Piezoelectric performance comparison diagram of the ultrasonic response piezoelectric hydrogel material (PVA / SA / Ce-CDs / PBT) and comparative examples 1-3;
[0031] Figure 7 Swelling ratio of the ultrasound-responsive piezoelectric hydrogel material (PVA / SA / Ce-CDs / PBT) and hydrogels in Comparative Examples 1-3 in PBS (pH 7.4) (n = 4) (*p < 0.05, **p < 0.01, ***p < 0.001);
[0032] Figure 8 Hemolysis comparison graph of the ultrasound-responsive piezoelectric hydrogel material (PVA / SA / Ce-CDs / PBT) and Comparative Examples 1-3 (A) and hemolysis rate comparison graph (B) (*p < 0.05, **p < 0.01, ***p < 0.001); Figure 8 Figure 8 Hemostatic performance of the ultrasound-responsive piezoelectric hydrogel material (PVA / SA / Ce-CDs / PBT) and control samples in a liver injury model;
[0033] Figure 9 Hemostatic time comparison of the hydrogel groups in the animal model (*p < 0.05, **p < 0.01, ***p < 0.001);
[0034] Figure 10 Blood loss amount comparison of the hydrogel groups in the animal model (*p < 0.05, **p < 0.01, ***p < 0.001);
[0035] Figure 11 Images of the scratch wound migration test of the hydrogel (scale bar = 200 μm).DETAILED DESCRIPTION
[0036] Figure 12 The present application is further illustrated by the following examples, which are not intended to limit the present application. Experimental materials
[0037]
[0038] Preparation of CeCDs:
[0039] Weigh 2.4 g of cerium nitrate hexahydrate (Ce(NO3)3·6H2O), 3.186 g of anhydrous citric acid (CA), and 2.994 g of p-phenylenediamine. Add the anhydrous citric acid to a beaker containing 60 ml of deionized water, stir until uniform, then add the previously weighed cerium nitrate hexahydrate and p-phenylenediamine, stir again until uniform, and then pour into a hydrothermal reaction kettle. Set the temperature to 180°C at the same time, react for 6 h, and then take out after cooling.
[0040] Example 1
[0041] Preparation of CeCDs:
[0042] Weigh 2.4 g of cerium nitrate hexahydrate (Ce(NO3)3·6H2O), 3.186 g of anhydrous citric acid (CA), and 2.994 g of p-phenylenediamine. Add the anhydrous citric acid to a beaker containing 60 ml of deionized water, stir until uniform, then add the previously weighed cerium nitrate hexahydrate and p-phenylenediamine, stir again until uniform, and then pour into a hydrothermal reaction kettle. Set the temperature to 180°C at the same time, react for 6 h, and then take out after cooling.
[0043] The obtained solution was poured into a filter flask for filtration. After the filtration was completed, it was loaded into a dialysis bag and dialyzed for 6 h. Finally, it was placed in a freeze dryer with a vacuum degree less than 20 Pa and a temperature of about -50°C for freeze-drying to obtain Ce-containing carbon dot powder. The TEM image and XPS image of the Ce-CDs are shown in Figure 3 and 4 .
[0044] Preparation of dopamine-modified barium titanate:
[0045] 2 g of BTO powder and 0.49 g of Tris Base powder were placed in 400 ml of deionized water and ultrasonically treated in an ultrasonic machine with a power of 40 kHz for 30 min to ensure uniform dispersion of BTO in the suspension. Then 3.6 g of dopamine hydrochloride was added to the above suspension, which was stirred at room temperature for 24 h to obtain a dopamine-modified barium titanate aqueous solution. Subsequently, it was centrifuged at 6000 r / min for ten minutes by a high-speed centrifuge, the supernatant was discarded, and the centrifuged liquid was placed in a vacuum oven at 60°C for drying overnight. The obtained solid was ground to obtain dopamine-modified barium titanate powder. The TEM image of the dopamine-modified barium titanate (PBT) is shown in Figure 5 .
[0046] Preparation of piezoelectric hydrogel material:
[0047] First, 3.2 g of polyvinyl alcohol (PVA) was added to a beaker containing 40 ml of deionized water, and then the beaker was placed in an oil bath environment at 90°C, and stirring was continuously performed for 3 h. After the stirring was completed, 0.8 g of dopamine-modified barium titanate and 0.04 g of Ce-containing carbon dots were sequentially added to the beaker, and then fully stirred to uniformly mix them.
[0048] After that, the temperature of the oil bath was reduced to 60°C, and 0.8 g of anhydrous calcium chloride was added to the beaker. After fully stirring, 0.8 g of sodium alginate (SA) was slowly added, and then stirring was continuously performed for 20 min until the sodium alginate was completely dissolved in the solution. Then, the solution was ultrasonically treated in an ultrasonic machine with a power of 40 kHz for 30 min to ensure that the bubbles in the solution completely disappeared.
[0049] Subsequently, the obtained mixed solution was poured into a culture dish, and after it was cooled to room temperature, the culture dish was placed in a freezing environment at -18°C, taken out after 8 h, and placed in a room temperature environment for thawing for 2 h. The freezing and thawing operation was repeated for 3 times according to the above operation to complete the freeze-thaw cycle. The piezoelectric hydrogel material was stored in a refrigerator at 4°C, so that a piezoelectric response hydrogel wound dressing was obtained, which can be directly applied to wound healing. The SEM photos of the ultrasonic response piezoelectric hydrogel material are shown in Figure 1 and 2 .
[0050] Comparative Example 1
[0051] The difference compared to Example 1 is that:
[0052] First, 3.2 g of polyvinyl alcohol (PVA) was added to a beaker containing 40 ml of deionized water, and then the beaker was placed in an oil bath at 90 °C, and stirring was continuously performed for 3 h. After the 3 h stirring was completed, the temperature of the oil bath was lowered to 60 °C, and then 0.8 g of anhydrous calcium chloride was added to the beaker, and after being stirred well, 0.8 g of sodium alginate (SA) was slowly added, and stirring was continued for 20 min until the sodium alginate was completely dissolved in the solution. Thereafter, the solution was ultrasonically treated in an ultrasonic machine at a power of 40 kHz for 30 min to completely remove the gas bubbles present in the solution.
[0053] Next, the resulting mixed solution was gently poured into a culture dish, and after being cooled to room temperature, the culture dish was placed in a freezing environment at -18 °C for 8 h, and then taken out and thawed at room temperature for 2 h. The freezing and thawing process was repeated 3 times to complete the freeze-thaw cycle. Finally, the hydrogel obtained after the series of processes was stored in a refrigerator at 4 °C, and thus the hydrogel control sample 1 was obtained.
[0054] Comparative Example 2
[0055] The difference compared to Example 1 is that:
[0056] First, 3.2 g of polyvinyl alcohol (PVA) was added to a beaker containing 40 ml of deionized water, and then the beaker was placed in an oil bath at 90 °C, and stirring was continuously performed for 3 h. After the 3 h stirring was completed, the temperature of the oil bath was lowered to 60 °C, and then 0.8 g of anhydrous calcium chloride was added to the beaker, and after being stirred well, 0.8 g of sodium alginate (SA) was slowly added, and stirring was continued for 20 min until the sodium alginate was completely dissolved in the solution. Thereafter, the solution was ultrasonically treated in an ultrasonic machine at a power of 40 kHz for 30 min to completely remove the gas bubbles present in the solution.
[0057] Comparative Example 3
[0058] The difference compared to Example 1 is that:
[0059] First, 3.2 g of polyvinyl alcohol (PVA) was weighed into a beaker containing 40 ml of deionized water and placed in a 90 °C oil bath with continuous stirring for 3 h. Next, 0.8 g of dopamine-modified barium titanate was added and stirred until uniform, and the oil bath was then cooled to 60 °C. 0.8 g of anhydrous calcium chloride was added and stirred thoroughly, and then 0.8 g of sodium alginate (SA) was slowly added and stirred for 20 min until it was fully incorporated. The solution was then treated with ultrasound in a 40 kHz ultrasonic machine for 30 min to remove bubbles. Next, the mixed solution was poured into a culture dish, cooled to room temperature, and placed in a -18 °C environment for 7-8 h. It was then removed and thawed at room temperature for 2 h, and the freeze-thaw cycle was repeated three times. Finally, the hydrogel was stored in a 4 °C refrigerator to obtain the hydrogel control sample 3.
[0060] Experimental tests:
[0061] The control sample and the experimental sample were connected to an electrochemical workstation, respectively, to detect their piezoelectric properties, as shown in Figure 6 . Specifically, the ultrasonic machine was operated at a power of 40 kHz for ten seconds and then paused for ten seconds for one minute, and the effect of ultrasound on the piezoelectric properties of each sample was investigated through such a cycle. The experimental results showed that the PVA / SA composite material could produce a relatively weak electric signal under the stimulation of ultrasound. However, when Ce-CDs and PBT were introduced into the system to form a PVA / SA / Ce-CDs / PBT composite system, the intensity of the electric signal produced was significantly improved. This is because Ce-CDs have a large interfacial area, which can cause high interfacial polarization and multiple scattering of ultrasound within the material, thereby more effectively improving the intensity of the ultrasonic response signal of PBT.
[0062] An appropriate water vapor transmission rate can create a moist environment for the wound, prevent the accumulation of exudates, and promote gas exchange between the wound surface and the outside world, thereby creating good conditions for the growth of fibroblasts and epithelial cells. As shown in Figure 7 , the water vapor transmission rate of each group of hydrogels remained in the range of 4000 g / m 2 / day to 6000 g / m 2 / day, while the water vapor transmission rate of the blank group was 7400 g / m 2 / day. Previous studies have shown that the water vapor transmission rate of healthy and undamaged skin is generally in the range of 4800-7000 g / m 2The water vapor transmission rate of the PVA / SA / CeCDs / PBT hydrogel is 0.5 g / m2 / day, but for the injured skin, the water vapor transmission rate can increase by 125 times or even more depending on the thickness of the wound. Therefore, the PVA / SA / CeCDs / PBT hydrogel has good air permeability and moisturizing capacity, can create a moist environment for the wound, and is conducive to the exchange of oxygen between the wound and the outside world, which is beneficial to promote wound healing.
[0063] To evaluate the hemocompatibility of the hydrogel, we performed a hemolysis experiment. According to the ISO / TR 7406.53 standard issued by the International Organization for Standardization, the safety threshold for hemolysis induced by biomaterials is 5%. From the results shown in FIG. 9, it can be seen that the hemolysis rate of all hydrogels is less than 2%, which indicates that they have good red blood cell compatibility. Figure 8 A and Figure 8 B can be seen that the hemolysis rate of all hydrogels is less than 2%, which indicates that they have good red blood cell compatibility.
[0064] Figure 9 、 10 and 11 presents the in vivo hemostatic effect of the hydrogel in a rat liver hemorrhage model. Compared with the blank group, the amount of bleeding at the site of liver injury of the rats was significantly reduced from 750 mg to 175 mg after the addition of the PVA / SA / CeCDs / PBT hydrogel. At the same time, compared with the blank group, the hemostatic time of the PVA / SA / CeCDs / PBT hydrogel used in the liver injury site of the rats was shortened from 320 seconds to 100 seconds. This shows that the PVA / SA / CeCDs / PBT hydrogel can enrich platelets, blood cells and coagulation-related proteins by absorbing blood from the wound, thereby achieving rapid hemostasis and accelerating the formation of blood clots on the wound surface. At the same time, the absorption of blood by the PVA / SA / CeCDs / PBT hydrogel in the bleeding area will increase its own weight, thereby exerting pressure on the damaged blood vessels to reduce the amount of bleeding and further promote the hemostatic process.
[0065] The improvement of the migration ability of fibroblasts is beneficial to skin tissue regeneration. Therefore, we used L929 fibroblasts to perform an in vitro scratch test to characterize the cell recruitment ability of the hydrogel. After using different hydrogel extracts to culture the cells for one day, the cells in the scratch area showed different degrees of migration. After ultrasonic stimulation, the migration area of the cells treated with the PVA / SA / CeCDs / PBT hydrogel was larger than that of the control group (see Figure 12 ), showing a stronger migration ability.
[0066] The above shows and describes the basic principles, main features and advantages of the present application. However, the above is only a specific embodiment of the present application, and the technical features of the present application are not limited thereto. Any other embodiments obtained by those skilled in the art without departing from the technical solutions of the present application should be covered in the patent scope of the present application.
Claims
1. An ultrasonic responsive piezoelectric hydrogel material, characterized in that, Consists of polyvinyl alcohol, sodium alginate, anhydrous calcium chloride, dopamine modified barium titanate and cerium doped carbon dots, and forms a piezoelectric network through freeze-thaw cycles to generate a micro-current under ultrasonic stimulation to promote wound healing.
2. The ultrasound-responsive piezoelectric hydrogel material of claim 1, wherein, The mass ratio of polyvinyl alcohol, sodium alginate, anhydrous calcium chloride, dopamine modified barium titanate and cerium doped carbon dots is 80:20:20:20:
1.
3. The method of producing an ultrasonic response piezoelectric hydrogel material according to claim 1 or 2, characterized by, The method comprises the following steps: Step 1, polyvinyl alcohol, deionized water is placed in a beaker and heated and stirred, then dopamine modified barium titanate and cerium doped carbon dots are sequentially added, fully stirred and uniformly mixed; Step 2, after cooling, anhydrous calcium chloride is added to the beaker, fully stirred and uniformly mixed, then sodium alginate is slowly added and stirred, the solution is ultrasonically treated after the sodium alginate is completely dissolved in the solution; Step 3, the mixed solution obtained in step 2 is poured into a culture dish and subjected to freeze-thaw cycles to obtain a piezoelectric hydrogel material.
4. The method of claim 3, wherein the ultrasound-responsive piezoelectric hydrogel material is prepared by the steps of: In step 1, the mass ratio of polyvinyl alcohol, dopamine modified barium titanate and Ce carbon dots is 80:20:1; the heating and stirring condition is 90℃ oil bath and stirring for 3h.
5. The method of claim 3, wherein the ultrasound-responsive piezoelectric hydrogel material is prepared by the steps of: In step 1, the preparation method of dopamine modified barium titanate is as follows: BTO powder, Tris Base powder and deionized water are uniformly mixed under ultrasonic to obtain a suspension; then dopamine hydrochloride is added to the suspension and stirred to obtain a dopamine modified barium titanate aqueous solution; subsequently, the liquid centrifuged out is dried by a high-speed centrifuge to obtain dopamine modified barium titanate, wherein the mass ratio of BTO powder, Tris Base powder and dopamine hydrochloride is 2:0.49:3.
6.
6. The method of claim 3, wherein the ultrasound-responsive piezoelectric hydrogel material is prepared by the steps of: In step 1, the preparation method of cerium doped carbon dots is as follows: Anhydrous citric acid and deionized water are mixed and stirred uniformly; then cerium nitrate hexahydrate and p-phenylenediamine are added respectively, stirred uniformly and heated to react; the obtained solution is subjected to suction filtration, dialysis and freeze-drying to obtain cerium doped carbon dots, wherein the mass ratio of cerium nitrate hexahydrate, anhydrous citric acid and p-phenylenediamine is 2.4:3.186:2.
994.
7. The method of claim 7, wherein the ultrasound-responsive piezoelectric hydrogel material is prepared by the steps of: The heating reaction condition is 180℃ for 6h.
8. The method of claim 3, wherein the ultrasound-responsive piezoelectric hydrogel material is prepared by the steps of: In step S2, the mass ratio of polyvinyl alcohol, anhydrous calcium chloride and sodium alginate is 4:1:1, and the temperature after cooling is 60℃.
9. The method of claim 3, wherein the ultrasound-responsive piezoelectric hydrogel material is prepared by the steps of: In step 3, the freeze-thaw condition is to be placed in a-18℃ freezing environment for 8h and then thawed at room temperature for 2h.
10. Use of the material of claim 1 or 2 in a medical dressing for promoting wound healing.