Molecular ferroelectric hydrogel patch, preparation method and application thereof

Abstract

The application discloses a molecular ferroelectric hydrogel patch, a preparation method and application thereof; a piezoelectric active component in the molecular ferroelectric hydrogel patch is a ferroelectric molecular crystal HOCH2(CF2)3CH2OH (referred to as HFPD), the crystal has a piezoelectric coefficient d 33 up to 138 pC / N, has good biodegradability, and can generate active oxygen under the action of ultrasonic waves; a preparation step comprises the following steps: HFPD single crystals are prepared by using a solution diffusion method; acrylic acid, polyvinyl alcohol (PVA), oxoglutaric acid, polyethylene glycol dimethacrylate and the HFPD single crystals are mixed, and the HFPD piezoelectric hydrogel patch is obtained through ultraviolet curing. α The application combines the HFPD crystal with a hydrogel matrix, and constructs the molecular ferroelectric hydrogel patch which has high piezoelectric activity, flexibility and degradability. The preparation process of the application adopts a solution method, and is simple and easy to operate, and has mild conditions, and is easy to scale up.

Description

Technical Field

[0001] This invention belongs to the field of piezoelectric materials technology, and relates to a molecular ferroelectric hydrogel patch, its preparation method and application; specifically, it relates to a preparation method and application of a molecular ferroelectric hydrogel patch with high piezoelectricity and biodegradability. Background Technology

[0002] Piezoelectric materials possess electromechanical conversion properties and are widely used in sensing, actuation, and energy conversion. In recent years, with the rapid development of biomedical engineering, transient implantable medical devices have attracted increasing attention. These devices can naturally degrade in vivo after fulfilling their intended function, avoiding the risks of secondary surgery and chronic inflammation and immune rejection. Therefore, stringent requirements are placed on the biocompatibility, biodegradability, and mechanical flexibility of the materials. However, while traditional inorganic piezoelectric materials (such as lead zirconate titanate (PZT) and barium titanate (BTO) have excellent performance, their applications are limited due to the presence of toxic heavy metals and their non-degradability. Ferroelectric polymers (such as polyvinylidene fluoride (PVDF)) possess flexibility but are also non-degradable, making them unsuitable for transient implantation. In contrast, molecular-based ferroelectrics combine advantages such as solution processability, tunable structure, good biocompatibility, low acoustic impedance, and degradability, making them highly promising for the application of transient implantable piezoelectric devices. However, there is still a lack of piezoelectric crystals that possess both excellent piezoelectric properties and good biocompatibility. Furthermore, most existing molecular ferroelectric materials exist in rigid crystal form, making it difficult to directly adapt to the flexibility and fit required for skin-attachment or implantation scenarios. Summary of the Invention

[0003] Purpose of the invention: The purpose of this invention is to provide a molecular ferroelectric hydrogel patch that combines a molecular ferroelectric crystal with high piezoelectricity with a hydrogel matrix to construct a patch that has high piezoelectric activity, good biocompatibility, biodegradability and mechanical flexibility.

[0004] Another object of the present invention is to provide a method for preparing the molecular ferroelectric hydrogel patch.

[0005] A third objective of this invention is to provide specific applications of the molecular ferroelectric hydrogel patches prepared by this method.

[0006] The technical solution of the present invention is: a molecular ferroelectric hydrogel patch of the present invention, comprising a three-dimensional hydrophilic polymer network and HFPD crystal material loaded or dispersed in the three-dimensional hydrophilic polymer network as a piezoelectric active component; The HFPD crystal material is HOCH2(CF2)3CH2OH, namely 2,2,3,3,4,4-hexafluoropentane-1,5-diol, and its structural formula is shown below: .

[0007] Furthermore, the preparation method of the molecular ferroelectric hydrogel patch includes the following steps: Step (1) Preparation of HFPD single crystals: Dissolve HFPD raw material in ethyl acetate, sonicate to dissolve, add petroleum ether to form a layered system, let stand and slowly evaporate to obtain colorless HFPD single crystals; Step (2) Preparation of hydrogel precursor solution: Acrylic acid, PVA, α - Ketoglutaric acid and polyethylene glycol dimethacrylate are dissolved in deionized water, stirred evenly, and then added to the colorless HFPD single crystals prepared in step (1). The mixture is sealed, heated and stirred to obtain a clear solution. Step (3) Preparation of hydrogel precursor solution: Add N-hydroxysuccinimide acrylate to the clear solution and mix well to obtain hydrogel precursor solution; Step (4) Curing and molding: The hydrogel precursor solution obtained in step (3) is dropped into the mold and cured by ultraviolet light to finally obtain the molecular ferroelectric hydrogel patch.

[0008] Furthermore, the concentration of the HFPD raw material in ethyl acetate in step (1) is 0.67 g / mL; The amount of petroleum ether added is 6 mL; The static setting time is 14 days (two weeks).

[0009] Furthermore, the crystal growth temperature of the HFPD colorless single crystal obtained in step (1) is 20-30℃; the humidity is 80-90%; and the crystal size is 1mm × 1mm × 3mm.

[0010] Furthermore, the molecular weight of the PVA mentioned in step (2) is 146,000-186,000; The acrylic acid, PVA, α The masses of β-ketoglutaric acid and polyethylene glycol dimethacrylate are 1.75 g, 0.35 g, 0.01 g and 0.0025 g, respectively.

[0011] Furthermore, the mass of the crystal material of the HFPD single crystal obtained in step (2) is 1.06g.

[0012] Furthermore, the temperature of the sealing film heating and stirring in step (2) is 50°C, and the material used for sealing film is polyvinyl chloride.

[0013] Furthermore, the mass of the N-hydroxysuccinimide acrylate added in step (3) is 0.15 g.

[0014] Furthermore, the mold described in step (4) is made of polytetrafluoroethylene, with dimensions of 40mm × 40mm and a depth of 5mm; The ultraviolet light parameters are 365nm, 12W, and the irradiation time is 20 minutes.

[0015] Furthermore, the molecular ferroelectric hydrogel patch prepared by the method can be used in the preparation of piezoelectric catalytic materials, biomechanical sensors, or wearable electronic devices.

[0016] Beneficial Effects: Compared with the prior art, the present invention has the following significant advantages: The present invention uses a simple solution method to prepare HOCH2(CF2)3CH2OH (HFPD) crystal material and hydrogel patch, without the need for stretching polarization treatment. The piezoelectric constant of the prepared HFPD crystal under unpolarized conditions is... d 33 That is, it reaches approximately 138 pC / N, which is significantly better than existing technologies such as polyvinylidene fluoride (PVDF, approximately 28 pC / N) and γ - Glycine (10.4 pC / N). HFPD-based hydrogel patches combine good biocompatibility with considerable piezoelectric properties. d 33 =9 pC / N). In summary, this invention provides an ideal class of bio-friendly piezoelectric materials for piezoelectric catalytic materials, biomechanical sensors, or wearable electronic devices. Attached Figure Description

[0017] Figure 1 This is an operation flowchart of the present invention; Figure 2 The DSC of the ferroelectric HFPD in this invention and ε ´- T Dependency (along) b (Axis) spectrum; Figure 3 This is the hysteresis loop spectrum of the ferroelectric HFPD along the

[001] direction in this invention; Figure 4 This is a measurement diagram of the piezoelectric coefficient of the HFPD hydrogel patch in this invention; Figure 5 These are fluorescence spectra of the reaction between TA and •OH in this invention, wherein: (a) is the fluorescence spectrum under conditions of ultrasound without HFPD; (b) is the fluorescence spectrum under conditions of ultrasound with HFPD. Figure 6 This is a schematic diagram of the biocompatibility experimental results of the ferroelectric HFPD in this invention. Detailed Implementation

[0018] The specific technical solution of the present invention will be further described in detail below with reference to specific examples.

[0019] As shown in the figure, the fluorinated diol molecular piezoelectric material (i.e. molecular ferroelectric hydrogel patch) of the present invention includes a three-dimensional hydrophilic polymer network and HFPD crystal material loaded in situ or dispersed in the three-dimensional hydrophilic polymer network as a piezoelectric active component. The molecular piezoelectric material (HFPD crystal material) is HOCH2(CF2)3CH2OH, i.e., 2,2,3,3,4,4-hexafluoropentane-1,5-diol, with the following structural formula: .

[0020] It should be noted that the aforementioned HFPD ( n =3) This is merely an example; the scope of protection of this invention should be extended to the general formula HOCH2(CF2). n All compounds covered by CH2OH (fluorinated diols, piezoelectric materials), among which n It is an odd number; Specifically, the fluorinated diol-based piezoelectric materials include, but are not limited to: n When =1: 2,2-difluoro-1,3-propanediol (HOCH2CF2CH2OH); n =3: 2,2,3,3,4,4-hexafluoropentane-1,5-diol (HOCH2(CF2)3CH2OH); n =5: 2,2,3,3,4,4,5,5,6,6-decafluoro-1,7-heptanediol (HOCH2(CF2)5CH2OH); n =7: 2,2,3,3,4,4,5,5,6,6,7,7,8,8-tetradecano-1,9-nonanediol (HOCH2(CF2)7CH2OH).

[0021] The structural features of the above compounds are: each molecule contains a hydroxymethyl (CH2OH) group at both ends, with an odd number of CF2 polar units in the middle; this structure endows the molecule with a permanent electric dipole moment, while the terminal hydroxyl groups can form an ordered two-dimensional network through hydrogen bonding, giving the material good solution processability, biocompatibility, and biodegradability. The odd number of CF2 units effectively prevents dipole cancellation, ensuring that the material exhibits macroscopic piezoelectricity and ferroelectricity.

[0022] The aforementioned fluorinated diol-based piezoelectric materials all possess terminal hydroxyl groups, which can form stable composite systems with hydrogel matrices (such as polyvinyl alcohol, polyacrylic acid, etc.) through hydrogen bonding. Therefore, they are also suitable for preparing molecular ferroelectric hydrogel patches; combining different nThe compounds that are valuable can be introduced into the three-dimensional hydrophilic polymer network of hydrogels as piezoelectric active ingredients, giving hydrogel patches piezoelectric response, biodegradability and sonodynamic properties.

[0023] In particular, when n When piezoelectricity = 3 (HFPD), its piezoelectric properties are particularly outstanding: under unpolarized conditions, the piezoelectric coefficient is... d 33 Up to 138 pC / N, piezoelectric voltage constant g 33 Reaching 2450×10 -3 The piezoelectric response is achieved at V·m / N without the need for complex mechanical stretching and polarization treatment; this specific embodiment uses HFPD as a representative compound for illustration, but the scope of protection of this invention is not limited thereto, and the general formula HOCH2(CF2) is also applicable. n CH2OH ( n All compounds covered by the term "(odd number)" are within the scope of protection of this invention.

[0024] Example 1: A method for preparing a molecular ferroelectric crystal material with high piezoelectricity and biodegradability, comprising the following steps: Step (1): Add fluorinated diol-based piezoelectric materials to ethyl acetate, sonicate to dissolve, and obtain a clear solution; Step (2): Add the solution obtained in step (1) above into a glass tube, and then add petroleum ether to obtain a layered solution; Step (3): Allow the solution from step (2) to evaporate slowly, yielding colorless rod-shaped single crystals of fluorinated diol-based molecular piezoelectric material. n =3 (HFPD) crystal structure and cell parameters are as follows: Figure 1 As shown in Table 1; The general formula of the fluorinated diol piezoelectric material mentioned in steps (4) and (1) is HOCH2(CF2). n CH2OH, in which n It is an odd number.

[0025] Table 1. Unit cell parameters of crystalline HFPD ; Example 2: A method for preparing a molecular ferroelectric hydrogel patch with high piezoelectricity and biodegradability, comprising the following steps: Step (1): Dissolve acrylic monomers, vinyl polymers, photoinitiators, and crosslinking agents in an organic solvent, stir evenly, add the fluorinated diol molecular ferroelectric crystal material obtained in Example 1, seal the film, heat and stir to obtain a transparent solution; Step (2): Add AAC-NHS to the solution obtained in step (1), mix evenly to obtain a hydrogel precursor solution, drop it into a mold and cure it by ultraviolet light to obtain a hydrogel patch of fluorinated diol molecular piezoelectric material. The general formula of the fluorinated diol piezoelectric materials mentioned in steps (3) and (1) is HOCH2(CF2). n CH2OH, in which n It is an odd number.

[0026] The acrylic monomers mentioned include: acrylic acid, methacrylic acid, acrylamide, N-methacrylamide, N,N-dimethylacrylamide, etc. The ethylene-based polymers include: polyacrylamide, polyacrylic acid, polyN-methylacrylamide, polyethyleneimine, etc. The photoinitiator includes: α β-ketoglutaric acid, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone, lithium phenyl(2,4,6-trimethylbenzoyl)phosphate, etc.; The crosslinking agents include: polyethylene glycol dimethacrylate, N,N'-methylenebisacrylamide, ethylene glycol dimethacrylate, divinylbenzene, etc. The organic solvents include: water, methanol, DMF, ethanol, acetone, petroleum ether, diethyl ether, chloroform, trichloroethylene, formamide, ethylene glycol, methylacetamide, aminoethanol, acetic acid, propanol, butanol, DMSO, acetonitrile, aniline, ethylenediamine, morpholine, pyridine, THF, quinine, toluene, etc.

[0027] Application Example 1: Detection of the Reactive Oxygen Generation Ability of Fluorinated Diol Piezoelectric Materials (1) Mix the fluorinated diol molecular piezoelectric material with the prepared terephthalic acid (TA) aqueous solution; (2) The crystal is subjected to ultrasonic treatment using medical ultrasound equipment; (3) Take the TA aqueous solution after soaking and sonication, and filter the solution; take the filtrate and use a fluorescence spectrometer (Fluorolog-QM, Horiba) to detect the fluorescence intensity of the solution after the reaction; (4) The fluorescence intensity of the TA aqueous solution after ultrasonication was compared with that of the un-soaked fluorinated diol molecular piezoelectric material to test the ability of the fluorinated diol molecular piezoelectric material to generate active oxygen. (5) In step (1), the fluorinated diol-based piezoelectric material is HOCH2(CF2). n crystalline materials of CH2OH and their hydrogel patches, among which nThe number of crystals is odd, and the hydrogel patch contains the single crystal as a piezoelectric active component; the TA aqueous solution is 30 mL and contains 5 mM TA and 10 mM NaOH; (6) In step (2), the ultrasonic excitation condition is 3.0 W / cm. 2 , 1MHz.

[0028] Application Example 2: Detection of Reactive Oxygen Generation Capacity of HFPD Crystal Materials (1) Mix 0.1g of HFPD material with 30 mL of terephthalic acid (TA) aqueous solution, wherein the TA aqueous solution contains 5mMMTA and 10mM NaOH; (2) The mixture obtained in step (1) was subjected to ultrasonic treatment using medical ultrasound equipment under ultrasonic conditions of 3.0 W / cm. 2 1MHz, 50% duty cycle, processed at 25°C; (3) Take the ultrasonically treated TA aqueous solution and filter it. Take the filtrate and use a fluorescence spectrometer (Fluorolog-QM, Horiba) to detect the fluorescence intensity of the solution after the reaction (excitation wavelength 312nm, emission wavelength 426nm). (4) Compare the fluorescence intensity obtained in step (3) with the fluorescence intensity of TA aqueous solution without HFPD material but subjected to the same ultrasonic treatment to evaluate the ability of HFPD to generate reactive oxygen species. The test results are as follows: Figure 5 As shown.

[0029] Application Example 3: Testing the Biocompatibility of Fluorinated Diol Piezoelectric Materials (1) Cell culture: Mouse cranial preosteoblast cell line MC3T3-E1 cells, rat bone marrow mesenchymal stem cells (rBMSCs) and rat neural stem cells (NSCs) were placed in growth medium containing 10% fetal bovine serum and 1% penicillin-streptomycin, and cultured at 37°C and 5% CO2. (2) Cell viability assay: The cells obtained in step (1) were seeded into 96-well plates (5×10⁶ cells / wells). 3 After culturing for 24 hours, cells were added to culture medium containing 1, 5, and 10 μg / mL of fluorinated diol piezoelectric material, respectively, and incubated for another 24 hours. After washing with PBS, 10 μL of CCK-8 reagent was added to each well and incubated for 1 hour. The optical density at 450 nm was measured using a microplate reader. (3) Live / dead cell staining: After incubating the cells with 1, 5, or 10 μg / mL of fluorinated diol piezoelectric material for 24 hours, the cells were washed with PBS, stained with calcein-AM / PI, and observed using a laser scanning confocal microscope. (4) Phalloidin / DAPI staining: After cells were incubated with 1, 5, and 10 μg / mL fluorinated diol piezoelectric materials for 24 hours, they were washed with PBS, fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton X-100, stained with phalloidin / DAPI, and observed with a laser scanning confocal microscope. (5) In steps (2)-(4), the fluorinated diol molecular piezoelectric material is HOCH2(CF2). n crystalline materials of CH2OH and their hydrogel patches, among which n The number is odd, and the hydrogel patch contains the single crystal as a piezoelectric active component; the laser scanning confocal microscope is an Olympus 141 FV3000.

[0030] Application Example 4: Testing the Biocompatibility of HFPD Crystal Materials (1) Cell culture: Mouse cranial preosteoblast line MC3T3-E1 cells, rat bone marrow mesenchymal stem cells (rBMSCs) and rat neural stem cells (NSCs) were placed in growth medium containing 10% fetal bovine serum and 1% penicillin-streptomycin, and cultured at 37°C and 5% CO2. (2) Cell viability assay: The cells obtained in step (1) were seeded into 96-well plates (5×10⁶ cells / wells). 3 After culturing (cells / well) for 24 hours, medium containing 1, 5, and 10 μg / mL HFPD was added and incubated for another 24 hours. After washing with PBS, 10 μL of CCK-8 reagent was added to each well and incubated for 1 hour. The optical density at 450 nm was measured using a microplate reader. (3) Live / dead cell staining: After incubating the cells with 1, 5, and 10 μg / mL HFPD for 24 hours, the cells were washed with PBS, stained with calcein-AM / PI, and observed using a laser scanning confocal microscope; (4) Phalloidin / DAPI staining: After incubation with 1, 5, and 10 μg / mL HFPD for 24 hours, cells were washed with PBS, fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton X-100, stained with phalloidin / DAPI, and observed using a laser scanning confocal microscope. The test results are as follows: Figure 6 As shown; (5) In steps (2)-(4), the laser scanning confocal microscope is an Olympus 141 FV3000.

Claims

1. A molecular ferroelectric hydrogel patch, characterized in that, It includes a three-dimensional hydrophilic polymer network and HFPD crystal materials that are in-situ loaded or dispersed in the three-dimensional hydrophilic polymer network as piezoelectric active components; The HFPD crystal material is HOCH2(CF2)3CH2OH, namely 2,2,3,3,4,4-hexafluoropentane-1,5-diol, and its structural formula is shown below: .

2. The method for preparing the molecular ferroelectric hydrogel patch according to claim 1, characterized in that, It includes the following steps: Step (1) Preparation of HFPD single crystals: Dissolve HFPD raw material in ethyl acetate, sonicate to dissolve, add petroleum ether to form a layered system, let stand and evaporate to obtain colorless HFPD single crystals; Step (2) Preparation of hydrogel precursor solution: Acrylic acid, PVA, α - Ketoglutaric acid and polyethylene glycol dimethacrylate are dissolved in deionized water, stirred evenly, and then added to the colorless HFPD single crystals prepared in step (1). The mixture is sealed, heated and stirred to obtain a clear solution. Step (3) Preparation of hydrogel precursor solution: Add N-hydroxysuccinimide acrylate to the clear solution and mix well to obtain hydrogel precursor solution; Step (4) Curing and molding: The hydrogel precursor solution obtained in step (3) is dropped into the mold and cured by ultraviolet light to finally obtain the molecular ferroelectric hydrogel patch.

3. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The concentration of the HFPD raw material in ethyl acetate in step (1) is 0.67 g / mL; The amount of petroleum ether added is 6 mL; The static setting time is 14 days.

4. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The crystal growth temperature of the colorless HFPD single crystal obtained in step (1) is 20-30℃; the humidity is 80-90%; and the crystal size is 1mm × 1mm × 3mm.

5. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The molecular weight of the PVA mentioned in step (2) is 146,000-186,000; The acrylic acid, PVA, α The masses of β-ketoglutaric acid and polyethylene glycol dimethacrylate are 1.75 g, 0.35 g, 0.01 g and 0.0025 g, respectively.

6. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The mass of the crystal material of the HFPD single crystal obtained in step (2) is 1.06g.

7. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The temperature for heating and stirring the sealing film in step (2) is 50°C, and the material used for sealing film is polyvinyl chloride.

8. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The mass of the N-hydroxysuccinimide acrylate added in step (3) is 0.15 g.

9. The method for preparing the molecular ferroelectric hydrogel patch according to claim 2, characterized in that, The mold mentioned in step (4) is made of polytetrafluoroethylene, with dimensions of 40mm × 40mm and a depth of 5mm; The ultraviolet light parameters are 365nm, 12W, and the irradiation time is 20 minutes.

10. The application of the molecular ferroelectric hydrogel patch prepared by the preparation method according to any one of claims 2-9 in the preparation of piezoelectric catalytic materials, biomechanical sensors or wearable electronic devices.

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