An oriented hydrogel dressing with piezoelectric effect and its preparation method and application

Abstract

The present invention discloses an oriented hydrogel dressing with piezoelectric effect. To obtain the oriented hydrogel dressing, BT@550nps with a mass percentage of 0.01wt% - 5wt%, PVDF with a mass percentage of 1wt% - 15wt%, and OSA with a mass percentage of 1wt% - 20wt% are added. The present invention also discloses a preparation method of an oriented hydrogel dressing with piezoelectric effect, which includes adding modified BaTiO3 nanoparticles into a solution of DMAc and deionized water, then successively adding OSA, PVDF and a cross-linking agent to mix to obtain a hydrogel, followed by drying and swelling in water to reach equilibrium to obtain the oriented hydrogel dressing. The oriented hydrogel dressing provided by the present invention has piezoelectric effect and oriented structure, and can promote the wound healing characteristics.

Description

Technical Field

[0001] The invention relates to medical supplies materials, in particular to an oriented hydrogel dressing with piezoelectric effect and a preparation method thereof. Background Art

[0002] There is an endogenous potential and transcutaneous current potential of 10-60mV in human skin. Piezoelectric materials with electrical response can be used to simulate and amplify the endogenous "bioelectricity" of sustained piezoelectric current to promote tissue repair and regeneration. Piezoelectric materials belong to a special class of materials with non-centrosymmetric crystal structures that are susceptible to mechanical stress.

[0003] Piezoelectric materials are divided into inorganic piezoelectric materials (such as zinc oxide, potassium sodium niobate, titanium dioxide, barium titanate, etc.) and polymer piezoelectric materials (such as polyvinylidene fluoride, polylactic acid, chitosan, etc.); among them, the piezoelectricity of polyvinylidene fluoride (PVDF) is related to its β phase content, its fiber morphology and crystallinity. The piezoelectric property comes from the oriented molecular dipole, which is formed by the mechanical deformation and polarization of the crystalline phase β. The α-type of PVDF crystal can be converted into the β-type under stretching, high temperature and electric field polarization, thereby obtaining high piezoelectricity. In addition to the β phase content and crystallinity, the uniaxial orientation of the β phase also makes a crucial contribution to the piezoelectricity of PVDF; non-centrosymmetric tetragonal BaTiO3 (BT) nanoparticles are a typical piezoelectric material. As a hydrophilic nanoparticle, tetragonal BaTiO3 can improve the hydrophilicity of PVDF and make the preparation of hydrogels possible.

[0004] Natural polymers have many advantages, such as wide sources, good biocompatibility, and functional modification on demand. Alginate (SA) is a biodegradable, negatively charged, bio-based natural polymer derived from seaweed. As a polyanion, alginate is very easy to cross-link with divalent cations to form a gel, and the hydrogel formed by it has a structure similar to the extracellular matrix (ECM). Therefore, SA is often used as a base framework material for gel materials. High molecular weight alginate has better gelling properties due to its longer chain segments; low molecular weight alginate has better biological activity and is more valuable in the biological field. Summary of the invention

[0005] The present invention designs and develops an oriented hydrogel dressing with piezoelectric effect. The purpose of the present invention is to obtain a hydrogel dressing with piezoelectric effect and oriented structure by using PVDF, OSA and BT@550nps as raw materials.

[0006] The present invention also designs and develops a method for preparing an oriented hydrogel dressing with a piezoelectric effect. The purpose of the present invention is to provide a method for preparing an oriented hydrogel dressing with a piezoelectric effect using PVDF, OSA, and BT@550nps as raw materials.

[0007] The technical solution provided by the present invention is:

[0008] An oriented hydrogel dressing with piezoelectric effect, comprising adding BT@550nps to a solution of DMAc and deionized water, then sequentially adding OSA, PVDF and a crosslinking agent to mix to obtain a hydrogel, and then rapidly drying the mixture and swelling it in water to reach equilibrium to obtain the oriented hydrogel dressing.

[0009] Preferably, the oriented hydrogel dressing is added with 0.01wt% to 5wt% of BT@550nps, 1wt% to 15wt% of PVDF, and 1wt% to 20wt% of OSA.

[0010] Preferably, the BT@550nps is obtained by adding BaTiO3 nanoparticles to an alkaline KH550 ethanol solution and then drying.

[0011] Preferably, the cross-linking agent is a CaSO4 suspension.

[0012] Preferably, the volume ratio of the DMAc to the deionized water is 1:1.

[0013] A method for preparing an oriented hydrogel dressing with piezoelectric effect comprises the following steps:

[0014] Step 1, dissolving Ba(OH)2·H2O in deionized water to obtain a first solution, dissolving tetrabutyl titanate in ethanol, and adding 35% ammonia solution to obtain a second solution, mixing the first solution and the second solution, adding triethanolamine to the mixture and heating the mixture in a Teflon reactor, washing and drying the obtained powder to obtain a white powder, subjecting the powder to thermal annealing treatment, and grinding the powder into fine powder after cooling to obtain tetragonal BaTiO3 nanoparticles;

[0015] Step 2: Add ethanol to deionized water under mechanical stirring, add KH550 to the solution under stirring, and continue stirring to obtain a third solution, add ammonia water to the deionized water until the pH value of the solution reaches 11, and obtain a fourth solution; mix the third solution and the fourth solution and mechanically stir, add the tetragonal BaTiO3 nanoparticles to the reaction under mechanical stirring, wash with deionized water, and dry in vacuum to obtain BT@550nps;

[0016] Step 3: After preparing a 4 wt% SA solution, adjust the pH of the solution to an acidic condition, add sodium periodate to the solution, react at room temperature in the dark, dialyze with distilled water, and freeze-dry to obtain OSA;

[0017] Step 4: adding the BT@550nps to a mixture of DMAc and deionized water, ultrasonically treating, adding OSA, and then stirring the mixture under heating conditions until it is completely dissolved, adding PVDF and stirring, and then adding a sufficient amount of CaSO4 suspension to obtain a composite gel, and drying after solvent exchange in deionized water to obtain a hydrogel dressing;

[0018] Step 5: After the two ends of the hydrogel dressing are clamped and dried in the air, the gel is expanded in water until equilibrium is reached to obtain the oriented hydrogel dressing.

[0019] Preferably, in the step 4, the mass fraction of the BT@550nps used is 0.01wt% to 5wt%.

[0020] Preferably, in the step 4, the mass fraction of the OSA used is 1 wt% to 20 wt%.

[0021] Preferably, in the step 4, the mass fraction of the PVDF used is 1 wt% to 15 wt%.

[0022] An application of an oriented hydrogel dressing with piezoelectric effect in preparing a medical dressing for wound repair, using the oriented hydrogel dressing with piezoelectric effect as claimed in claim 1.

[0023] The beneficial effects of the present invention are:

[0024] 1. The hydrogel dressing provided by the present invention can obtain an anisotropic hydrogel by limiting the deformation of the hydrogel in the length direction and then drying it in the air. In this process, a sufficiently high tensile stress is established along the length direction to align the polymer chains, and multi-scale fiber structures (from submicron to micro) are spontaneously formed in the bulk material. These structures are well retained in the swollen gel. The uniaxial orientation of the β phase of PVDF can make a crucial contribution to the piezoelectricity of PVDF.

[0025] 2. In the present invention, BaTiO3 nanoparticles play the role of heterogeneous nucleating agents in the crystallization process of PVDFβ phase, and act as a reinforcing agent to maintain the residual orientation of the β phase. 3-Aminopropyltriethoxysilane coupling agent (KH550) is equivalent to a bridge between BaTiO3 nanoparticles and PVDF, increasing the compatibility of BaTiO3 nanoparticles with PVDF and being able to transmit electric field polarization. KH550-modified BaTiO3 nanoparticles (BT@550nps) are grafted onto the OSA chain through Schiff bonds, which not only serve as cross-linking points to enhance the mechanical properties of the gel, but also improve the piezoelectric properties of the hydrogel dressing.

[0026] 3. In the present invention, the addition of SA reduces the hydrophobicity of PVDF and further reduces the possibility of phase separation of PVDF in the hydrogel. The oxidation of SA to oxidized sodium alginate (OSA) can reduce the molecular weight of sodium alginate and improve water solubility. OSA is also a natural cross-linking agent, which can avoid the addition of small molecule cross-linking agents. At the same time, the addition of OSA can greatly improve the solubility of PVDF in the mixed solution.

[0027] 4. In the present invention, DMAc is used as a solvent, which has low toxicity, good solubility in materials, and is easy to remove in the post-processing of the experiment. The obtained hydrogel is clamped and then dried and stretched to obtain an oriented structure. Then, through simple operations such as swelling in water, an oriented hydrogel dressing with piezoelectric effect can be obtained. The processing is simple, the preparation conditions are highly operational, and it is convenient for mass production in the future. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a SEM image of the BaTiO3 nanoparticles in Example 3 described in the present invention.

[0029] Figure 2 This is the SEM image of BT@550nps in Example 3 described in the present invention.

[0030] Figure 3 This is the infrared spectrum of BaTiO3 nanoparticles and BT@550nps in Example 3 described in the present invention.

[0031] Figure 4 This is a thermogravimetric curve of BT@550nps in Example 3 described in the present invention.

[0032] Figure 5 It is the infrared spectrum of SA and OSA in Example 3 described in the present invention.

[0033] Figure 6 2 are the NMR spectra of SA (upper) and OSA (lower) in Example 3 described in the present invention.

[0034] Figure 7 This is a schematic diagram of the oriented structure in Example 3 described in the present invention (the dotted line represents the PVDF molecular chain, and the solid line represents the oxidized sodium alginate molecular chain).

[0035] Figure 8 This is a SEM image of the oriented SPB hydrogel in Example 3 described in the present invention.

[0036] Fig. 9 Schematic diagram of the output voltage of the oriented SPB hydrogel in Example 3 described in the present invention. DETAILED DESCRIPTION

[0037] The present invention is further described in detail below in conjunction with the accompanying drawings so that those skilled in the art can implement the invention with reference to the description.

[0038] The present invention provides an oriented hydrogel dressing with piezoelectric effect, which comprises 0.01wt% to 5wt% of modified barium titanate nanoparticles (BT@550nps), 1wt% to 15wt% of polyvinylidene fluoride (PVDF), 1wt% to 20wt% of oxidized sodium alginate (OSA), and the remainder is a cross-linking agent; as a preferred embodiment, the cross-linking agent is a calcium sulfate suspension (CaSO4 suspension).

[0039] The present invention also provides a method for preparing an oriented hydrogel dressing with a piezoelectric effect, which comprises adding modified barium titanate nanoparticles (BT@550nps) to a solution of N,N-dimethylacetamide (DMAc) and deionized water, and then sequentially adding oxidized sodium alginate (OSA), polyvinylidene fluoride (PVDF) and a cross-linking agent to obtain a hydrogel, clamping and drying, and then expanding in water to reach equilibrium to obtain an oriented hydrogel dressing, which specifically comprises the following steps:

[0040] Step 1, preparing tetragonal BaTiO3 nanoparticles: dissolving Ba(OH)2·H2O in deionized water to obtain a first solution, dissolving tetrabutyl titanate in ethanol, and adding 35% ammonia solution to obtain a second solution, mixing the first solution and the second solution, mixing triethanolamine and adding the mixture to a Teflon reactor for heating and reaction, washing and drying the obtained powder to obtain a white powder, performing thermal annealing treatment, and grinding the powder into fine powder after cooling to obtain tetragonal BaTiO3 nanoparticles (BaTiO3 nanoparticles);

[0041] Step 2, preparing modified BaTiO3 nanoparticles: adding ethanol to deionized water under mechanical stirring, and continuing stirring for 10 minutes, adding 3-aminopropyltriethoxysilane coupling agent (KH550) to the solution under stirring, and continuing stirring to obtain a third solution, adding ammonia water to 500mL deionized water until the pH value of the solution reaches 11, to obtain a fourth solution; mixing the third solution and the fourth solution and mechanically stirring, adding tetragonal BaTiO3 nanoparticles to the final solution under mechanical stirring, washing with deionized water after reaction, and vacuum drying to obtain modified BaTiO3 nanoparticles (BT@550nps);

[0042] Step 3, preparing oxidized sodium alginate: after preparing a 4 wt % sodium alginate (SA) solution, adjusting the pH of the solution to 4, adding sodium periodate to the solution, reacting at room temperature in the dark, dialyzing with distilled water, and freeze-drying to obtain oxidized sodium alginate (OSA);

[0043] Step 4, preparing SPB hydrogel: adding BT@550nps to a mixture of DMAc and deionized water, after ultrasonic treatment, adding OSA, and then stirring the mixture under heating conditions until it is completely dissolved, adding PVDF and stirring, and then adding a sufficient amount of CaSO4 suspension to obtain a composite gel, and drying after solvent exchange in deionized water to obtain a hydrogel dressing (SPB hydrogel);

[0044] Step 5: Cut the SPB hydrogel dressing into rectangles and clamp both ends. After drying the gel in air, swell the gel in water until equilibrium is reached to obtain an oriented hydrogel dressing (oriented SPB hydrogel).

[0045] In another embodiment, in step one, the reaction is carried out in a Teflon reactor at 200° C. for 48 hours, and the thermal annealing treatment includes heating the powder in a tube furnace at 800° C. for 10 hours.

[0046] In another embodiment, in step 2, the vacuum drying condition is drying at 80° C. for 6 hours.

[0047] In another embodiment, in step 3, the molecular weight cut-off of the dialysis bag used for dialysis is M W =8000.

[0048] In another embodiment, in step four, the mass fraction of BT@550nps is 0.01wt% to 5wt%, the mass fraction of OSA is 1wt% to 20wt%, the mass fraction of PVDF is 1wt% to 15wt%, and the volume ratio of DMAc and deionized water is 1:1; wherein wt% is the ratio of the mass (g) of the added solute to the volume (mL) of the solvent.

[0049] In another embodiment, in step five, the SPB hydrogel is cut into a rectangle with a size of 1 cm×6 cm, and its two long ends are clamped using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm, and the gel is dried in the air (temperature and humidity conditions: temperature is 25°C, humidity is 40-60%).

[0050] Example 1

[0051] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0052] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0053] (2) Surface modification of BaTiO3

[0054] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0055] (3) Oxidation of sodium alginate

[0056] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0057] (4) Preparation of SPB hydrogel

[0058] ① Add 0.01wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 10wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 10wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain a white translucent SPB hydrogel.

[0059] (5) Preparation of oriented SPB gel

[0060] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0061] Example 2

[0062] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0063] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0064] (2) Surface modification of BaTiO3

[0065] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0066] (3) Oxidation of sodium alginate

[0067] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0068] (4) Preparation of SPB hydrogel

[0069] ① Add 0.1wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 10wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 10wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0070] (5) Preparation of oriented SPB gel

[0071] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0072] Example 3

[0073] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0074] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0075] (2) Surface modification of BaTiO3

[0076] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0077] (3) Oxidation of sodium alginate

[0078] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0079] (4) Preparation of SPB hydrogel

[0080] ① Add 1.0wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 10wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 10wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0081] (5) Preparation of oriented SPB gel

[0082] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0083] Example 4

[0084] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0085] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0086] (2) Surface modification of BaTiO3

[0087] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0088] (3) Oxidation of sodium alginate

[0089] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0090] (4) Preparation of SPB hydrogel

[0091] ① Add 1.0wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 1wt% OSA, and then heat and stir the mixture at 60°C until it is completely dissolved; ③ Add 10wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70°C, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0092] (5) Preparation of oriented SPB gel

[0093] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0094] Example 5

[0095] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0096] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0097] (2) Surface modification of BaTiO3

[0098] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0099] (3) Oxidation of sodium alginate

[0100] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0101] (4) Preparation of SPB hydrogel

[0102] ① Add 1.0wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 15wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 10wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0103] (5) Preparation of oriented SPB gel

[0104] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0105] Example 6

[0106] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0107] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0108] (2) Surface modification of BaTiO3

[0109] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0110] (3) Oxidation of sodium alginate

[0111] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0112] (4) Preparation of SPB hydrogel

[0113] ① Add 5wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 15wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 10wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0114] (5) Preparation of oriented SPB gel

[0115] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0116] Example 7

[0117] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0118] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0119] (2) Surface modification of BaTiO3

[0120] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0121] (3) Oxidation of sodium alginate

[0122] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0123] (4) Preparation of SPB hydrogel

[0124] ① Add 1.0wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 10wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 1wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0125] (5) Preparation of oriented SPB gel

[0126] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0127] Example 8

[0128] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0129] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0130] (2) Surface modification of BaTiO3

[0131] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0132] (3) Oxidation of sodium alginate

[0133] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0134] (4) Preparation of SPB hydrogel

[0135] ① Add 1.0wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 10wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 15wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0136] (5) Preparation of oriented SPB gel

[0137] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0138] Example 9

[0139] (1) Preparation of tetragonal BaTiO3 nanoparticles

[0140] ① Weigh 12.85g of Ba(OH)2·H2O and dissolve it in 25mL of deionized water to obtain solution A; ② Weigh 17.02g of tetrabutyl titanate and dissolve it in 20mL of ethanol, and add 7mL of 35% ammonia solution to obtain solution B; ③ After mixing solutions A and B, 5mL of triethanolamine was mixed and added to a 100mL Teflon reactor. After reacting at 200℃ for 48h, the obtained powder was washed and dried to obtain a white powder; ④ The BT nanoparticles were transformed from a cubic phase to a tetragonal phase with piezoelectric catalysis by thermal annealing. During the heat treatment process, the obtained BT powder was heated in a tube furnace at 800℃ for 10h, and then ground into a fine powder after natural cooling.

[0141] (2) Surface modification of BaTiO3

[0142] ① Add 50 mL of ethanol to 450 mL of deionized water under mechanical stirring and continue stirring for 10 minutes. ② Add 4 g of KH550 to the solution under stirring and continue stirring for 20 minutes. ③ Add ammonia water to 500 mL of deionized water until the pH value of the solution reaches 11. Mix the two solutions and stir mechanically for 1 hour. ④ Add 50 g of BT particles to the final solution under mechanical stirring and react for 6 hours to allow KH550 to react with the surface of BT particles. Then wash the reacted BT particles with deionized water and dry them in a vacuum oven at 80 ° C for 6 hours to obtain BT@550nps.

[0143] (3) Oxidation of sodium alginate

[0144] ① Prepare 100 mL of 4 wt% SA solution; then adjust the pH of the solution to 4. ② Add 0.8 g of sodium periodate to the solution and react at room temperature in the dark for 6 h; ③ Dialyze with distilled water (Mw=8000) for 5 d and freeze-dry to obtain OSA.

[0145] (4) Preparation of SPB hydrogel

[0146] ① Add 0.1wt% BT@550 nanoparticles to a mixture of DMAc and deionized water (v / v=5:5) and ultrasonically treat for 0.5h; ② Add 20wt% OSA, and then heat and stir the mixture at 60℃ until completely dissolved; ③ Add 15wt% PVDF and stir for 2h; ④ Add sufficient CaSO4 suspension to obtain OSA / PVDF composite gel modified with BT@550 nanoparticles; ⑤ Solvent exchange in deionized water for 1h, dry at 70℃, and repeat 3 times to remove the organic solvent DMAc to obtain SPB hydrogel.

[0147] (5) Preparation of oriented SPB gel

[0148] ① Cut the SPB gel (5 mm thick) into a rectangle of 1 cm × 6 cm and clamp its two long ends using a homemade bracket. After clamping, the effective length of the sample (the part exposed to the air) is 4 cm. ② Dry the gel in air (temperature: 25 ° C, humidity: 40-60%). After complete air drying, the gel swells in water until equilibrium is reached. ③ Repeat several times, and the final hydrogel prepared is called oriented SPB gel.

[0149] Test Case

[0150] In the present invention, by adjusting the addition amounts of PVDF, OSA, and BT@550nps, an oriented SPB gel with piezoelectric properties can be obtained. The properties of the oriented SPB gel of the present invention are tested as follows:

[0151] BT nanoparticles, BT@550 nanoparticles, and freeze-dried SPB hydrogel were observed using a scanning electron microscope (SEM) (FEIQuanta 250, the Netherlands). The dried samples were attached to a sample stage and gold-sprayed (Model 550; Electron Microscope Sciences), and then SEM images were taken.

[0152] After the samples were prepared by potassium bromide powder tableting method, BT nanoparticles, BT@550 nanoparticles, sodium alginate, and oxidized sodium alginate were tested using infrared spectroscopy scanning FT-IR (Nicolet 5700, Thermo Company, USA).

[0153] Thermogravimetric curves of BT@550nps were obtained using TGA (Q500, TA Instruments, New Castle, DE) at a heating rate of 10°C / min to 800°C.

[0154] Sodium alginate and oxidized sodium alginate were dissolved in deuterated water and NMR was obtained using AVANCE III 400MHz. 1 H NMR) spectroscopy.

[0155] The output voltage of the SPB hydrogel was measured by a Keithley 2450 multimeter under tensile (~2N) and compressive (~3N) strengths using an electronic universal testing machine (E44.104, MTS Systems Co., Ltd., China).

[0156] The test results are as follows:

[0157] In Example 3, Figure 1 , Figure 2As shown, it can be seen that the synthesized BaTiO3 nanoparticles are tetragonal phase with piezoelectric properties, and the structure of the tetragonal phase is not changed after modification with KH550.

[0158] like Figure 3 As shown, in the process of preparing tetragonal BaTiO3 nanoparticles and preparing BT@550nps, 562cm -1 The Ti-O bond is at 1429cm -1 It is the characteristic absorption peak of BT, 2924cm -1 、2854cm -1 The asymmetric stretching vibration peak of -CH3 is 3417 cm -1 is the stretching vibration peak of hydroxyl and amino groups, 1635cm-1 is the bending vibration peak of NH, 1200-1020cm -1 The broad peak at 1196 cm is the asymmetric stretching vibration peak of Si-OR. -1 and 980cm -1 The absorption peaks of Si-C and the deformation vibration peaks of Si-OH.

[0159] like Figure 4 As shown in the thermogravimetric curve of BT@550nps, it can be seen that the first section of weight loss corresponds to the hydroxyl groups on the surface of the nanoparticles, the second section of weight loss corresponds to the KH550 adsorbed on the surface of the nanoparticles, and the third section of weight loss corresponds to the successfully grafted KH550.

[0160] like Figure 5 , Figure 6 As shown, -CHO: 1730-1740cm -1 Due to the low degree of oxidation, the hemiacetal structure exists, the peak becomes smaller or even covered, and the hemiacetal protons generated by the aldehyde group and the hydroxyl group can be observed between δ=5.03 and 5.63ppm, and the generated aldehyde groups are all in the form of hemiacetal.

[0161] like Figure 7 As shown, the prepared SPB gel has a size of 6 cm × 1 cm × 5 mm (length × width × thickness) before drying, an effective size of 4 cm × 1 cm × 5 mm, and an effective length of 4 cm × 0.6 cm × 3 mm after drying. After drying, it changes from the original translucent to white opaque.

[0162] like Figure 8 As shown, it can be seen that the oriented SPB gel has an aligned fibrous oriented structure.

[0163] like Fig. 9As shown in the figure, the output voltage is between 10mV and 300mV, which is in line with the optimal voltage range for promoting wound healing. Female rats aged 6 weeks were anesthetized with intraperitoneal injection of sodium pentobarbital. After removing the dorsal hair, a circular full-thickness skin wound model with a diameter of 1cm was established at the dorsal spine of the rats (where the activity is large and the hydrogel is prone to deformation). The control group was treated with Tegaderm, and the experimental group was treated with SPB hydrogel and further fixed with 3M Tegaderm film. The wounds were observed and photographed once on the 1st, 3rd, 5th, 7th, and 14th days, and the wound area at different time points was measured using ImageJ software.

[0164] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes, and they can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and the illustrations shown and described herein.

Claims

1. A method for preparing an oriented hydrogel dressing having a piezoelectric effect, characterized in that: The steps include: Step 1: dissolving Ba(OH)2·H2O in deionized water to obtain a first solution, dissolving tetrabutyl titanate in ethanol, and adding 35% ammonia solution to obtain a second solution, mixing the first solution and the second solution, adding triethanolamine to the mixture and heating the mixture in a Teflon reactor, washing and drying the obtained powder to obtain a white powder, subjecting the powder to thermal annealing treatment, and grinding the powder into fine powder after cooling to obtain tetragonal BaTiO3 nanoparticles; Step 2: Add ethanol to deionized water under mechanical stirring, add KH550 to the solution under stirring, and continue stirring to obtain a third solution, add ammonia water to the deionized water until the pH value of the solution reaches 11, and obtain a fourth solution; mix the third solution and the fourth solution and mechanically stir, add the tetragonal BaTiO3 nanoparticles to the reaction under mechanical stirring, wash with deionized water, and vacuum dry to obtain BT@550 nps; Step 3: After preparing a 4 wt % SA solution, adjust the pH of the solution to an acidic condition, add sodium periodate to the solution, react at room temperature in the dark, dialyze with distilled water, and freeze-dry to obtain OSA; Step 4: adding the BT@550 nps to a mixture of DMAc and deionized water, ultrasonically treating, adding OSA, and then stirring the mixture under heating conditions until it is completely dissolved, adding PVDF and stirring, and then adding a sufficient amount of CaSO4 suspension to obtain a composite gel, and drying after solvent exchange in deionized water to obtain a hydrogel dressing; using a volume ratio of DMAc to deionized water of 1:1; Step 5: After the two ends of the hydrogel dressing are clamped and dried in the air, the gel is expanded in water until equilibrium is reached to obtain the oriented hydrogel dressing.

2. The method for preparing the oriented hydrogel dressing with piezoelectric effect according to claim 1, characterized in that: In the step 4, the mass fraction of the BT@550 nps used is 0.01wt% to 5wt%.

3. The method for preparing the oriented hydrogel dressing with piezoelectric effect according to claim 1 or 2, characterized in that: In the step 4, the mass fraction of the OSA used is 1wt% to 20wt%.

4. The method for preparing an oriented hydrogel dressing with piezoelectric effect according to claim 3, characterized in that: In the step 4, the mass fraction of the PVDF used is 1wt% to 15wt%.

5. An oriented hydrogel dressing with piezoelectric effect, characterized in that: The oriented hydrogel dressing with piezoelectric effect is prepared using the preparation method of claim 1.

6. Application of an oriented hydrogel dressing with piezoelectric effect in preparing a medical dressing for wound repair, characterized in that: Use the oriented hydrogel dressing with piezoelectric effect as claimed in claim 5.

Images