Ultrasonic piezoelectric composite material and preparation method thereof
By preparing a bilayer spun membrane through electrospinning and loading magnesium-containing compounds onto its surface, the problems of insufficient mechanical properties and bioactivity of piezoelectric composite membranes were solved, realizing the multifunctional application of ultrasonic piezoelectric composite materials in tissue repair.
Patent Information
- Application Number
- CN202511546773.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-28
- Publication Date
- 2026-02-24
AI Technical Summary
Existing piezoelectric composite membranes have problems with insufficient mechanical properties, bioactivity, and electrical stimulation signal intensity in tissue repair. Furthermore, existing ultrasonic piezoelectric composite materials have insufficient bioactivity, limited functionality, and their indications need to be expanded.
A bilayer composite material of disordered and ordered fiber spun membranes was prepared by electrospinning technology, and magnesium-containing compounds were loaded on the surface or magnesium oxide layers were deposited to form an ultrasonic piezoelectric composite material. The ultrasonic stimulation generates electrical signals and releases magnesium ions to improve the tissue damage environment.
It improves the performance of ultrasonic piezoelectricity, enhances biological function, promotes tissue repair, and is suitable for the repair of periosteal, spinal cord injuries and traumatic brain injuries, achieving flexible control of non-invasive electrical stimulation.
Smart Images
Figure CN121550422A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of tissue repair technology, and particularly relates to an ultrasonic piezoelectric composite material and its preparation method. Background Technology
[0002] The electrical microenvironment is considered a key determinant of various pathophysiological processes, including tissue homeostasis and wound healing. The application of electricity to cells and tissues via external devices or based on biomaterials has attracted widespread attention. Biomaterial-based electrostimulation technology plays a crucial role in repairing damaged tissues. There are two main technical approaches to achieving electrostimulation through biomaterials: the first is conductive biomaterials, which integrate conductive elements into tissue scaffolds to promote intercellular electrical signal transmission and stimulation. However, standards for this type of interventional external power device have not been established, and it can inevitably cause damage and inflammation, severely limiting its clinical application. The second type is responsive electroactive biomaterials, which can autonomously generate electricity in response to diverse external signals such as light, magnetic fields, and mechanical forces. With the continuous development of biocompatible biomaterials, this field is constantly evolving. These materials can not only efficiently convert single stimuli but also achieve synergistic effects of multiple stimuli. In specific scenarios, the application effect of conductive biomaterials may be superior to that of responsive electroactive biomaterials because external stimuli may face impedance and signal attenuation issues, thus affecting actual effectiveness. Therefore, by finely adjusting the electrical stimulation parameters, optimizing the bioactive factors, and developing non-invasive implantable electrical stimulation biomaterial implantation devices with precise control functions, there is broad application potential.
[0003] Piezoelectric materials have shown great potential in addressing the challenges of invasive electrical signal transmission in regenerative medicine. These materials alter their internal charge distribution and generate an electric field simply by applying pressure. However, existing piezoelectric composite films suffer from limitations in mechanical properties, bioactivity, and electrical stimulation signal intensity, restricting their application in tissue repair. Barium titanate (BaTiO3, BTO) is a compound with excellent dielectric and ferroelectric properties, showing great potential in promoting piezoelectric bone regeneration. Multiple studies have shown that coating or embedding BTO nanoparticles with biomaterials can not only enhance their bioactivity but also generate electrical stimulation in response to ultrasound, promoting tissue healing. However, despite BTO's good biocompatibility, its bioactivity in tissue repair remains insufficient. Therefore, constructing ultrasonic piezoelectric composite materials with multiple bioactivities is of great significance in the field of tissue regeneration. The disadvantages of existing ultrasonic piezoelectric composite nanofiber materials are: (1) the intensity of the piezoelectric signal generated by ultrasonic stimulation is insufficient; (2) the single-layer ordered orientation polymer piezoelectric composite film has anisotropy, and the mechanical properties of different directions are very different; (3) the existing ultrasonic piezoelectric composite materials have insufficient bioactivity and single function, and the indications need to be further expanded. Summary of the Invention
[0004] To address the aforementioned technical problems, this invention provides an ultrasonic piezoelectric composite material and its preparation method. The composite material provided by this invention combines nanofibers with ultrasonic piezoelectric properties with nanoparticles possessing ultrasonic piezoelectric properties, while simultaneously loading bioactive magnesium-containing nanomaterials or deposited magnesium oxide. This composite material can simulate the generation of bioelectric signals through non-invasive ultrasound induction. Simultaneously, by ultrasound-regulated release of magnesium-containing compounds or magnesium oxide layers loaded on the surface of the piezoelectric material, it improves the inflammatory microenvironment of tissue damage, promoting multi-stage repair processes from cell migration and proliferation to tissue remodeling. This has clinical value in the fields of chronic wound, fracture, and nerve injury repair.
[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: On one hand, the present invention provides an ultrasonic piezoelectric composite material, comprising a first thin film layer and a second thin film layer stacked together; the first thin film layer and the second thin film layer are made of a polymer doped with barium titanate; the first thin film layer is a disordered fiber spun film, and the second thin film layer is an ordered fiber spun film; the surface of the first thin film layer and / or the second thin film layer is further loaded with a magnesium-containing compound, or, the surface of the first thin film layer and / or the second thin film layer is deposited with a magnesium oxide layer.
[0006] In a preferred embodiment, the polymer is selected from either polylactic acid or polycaprolactone; Preferably, the polylactic acid has a weight-average molecular weight of 100,000 to 300,000, and more preferably 170,000 to 260,000. Preferably, the polycaprolactone has a weight-average molecular weight of 80,000 to 300,000, and more preferably 100,000 to 200,000. Preferably, the barium titanate is tetragonal barium titanate nanoparticles with a particle size of 100~350 nm; Preferably, the magnesium-containing nanocompound is selected from at least one of magnesium-aluminum layered bimetallic hydroxides (MgAl-LDHs), magnesium oxide nanoparticles, and polyphenol-modified MgO nanoparticles; Preferably, the magnesium-aluminum layered bimetallic hydroxide has a sheet diameter of 0.6 to 4 μm, more preferably 0.6 to 2 μm.
[0007] In a preferred embodiment, the mass ratio of barium titanate to polymer in the first thin film layer and / or the second thin film layer is 0.08~0.375:1; In a preferred embodiment, the thickness ratio of the first thin film layer to the second thin film layer is 0.5 to 2:1; Preferably, the thickness ratio of the first thin film layer to the deposited magnesium oxide layer is 1000~4000:1; Preferably, in the second thin film layer, the fiber orientation is perpendicular to the thickness direction of the second thin film layer.
[0008] In another aspect, the present invention provides a method for preparing the above-mentioned ultrasonic piezoelectric composite material, comprising the following steps: (1) A disordered first thin film layer is prepared by electrospinning with a polymer solution containing barium titanate; an ordered second thin film layer is prepared on the first thin film layer by electrospinning with a polymer solution containing barium titanate; wherein the polymer solution contains barium titanate; Alternatively, an ordered second thin film layer is prepared by electrospinning using a polymer solution containing barium titanate; a disordered first thin film layer is then prepared on the second thin film layer by electrospinning using a polymer solution containing barium titanate; wherein the polymer solution contains barium titanate. (2) Immerse the product of step (1) in a magnesium compound solution, or deposit a magnesium oxide layer on the first thin film layer and / or the second thin film layer.
[0009] In a preferred embodiment, the solvent of the polymer solution is selected from at least one of hexafluoroisopropanol, dichloromethane, and trichloromethane; In a preferred embodiment, the process parameters for preparing the disordered first thin film layer by electrospinning are as follows: The flow rate of the spinning solution is constant, ranging from 0.8 to 1 mL / h; The distance between the spinneret and the receiving device is 12-13 cm; Positive voltage is 16~20 kV, negative voltage is -2.5~-2 kV; The receiving device rotates at 500~800 rpm.
[0010] In a preferred embodiment, the process parameters for preparing the ordered second thin film layer by electrospinning are as follows: The flow rate of the spinning solution is constant, ranging from 0.8 to 1 mL / h; The distance between the spinneret and the receiving device is 12-13 cm; Positive voltage is 30~35 kV, negative voltage is -14~-10 kV; The receiving device rotates at 3000~6000 rpm.
[0011] In a preferred embodiment, in step (2), the total mass ratio of the first thin film layer and the second thin film layer to the mass ratio of the magnesium-containing compound is 6 to 9:1.
[0012] In some specific embodiments, the soaking is carried out under stirring conditions; the stirring is low-speed stirring, with a rotation speed ≤100 rpm; and the soaking time is 12~24 h.
[0013] In some specific embodiments, the concentration of the magnesium compound in the magnesium compound solution is 0.9% to 3%.
[0014] In some specific embodiments, the soaking process further includes post-treatment of washing and drying.
[0015] The above technical solution has the following advantages or beneficial effects: This invention utilizes electrospinning to prepare a bilayer membrane with both disordered and ordered fiber spun membranes from barium titanate, which possesses ultrasonic piezoelectric properties, and a polymer. The ordered fiber spun membrane further enhances the ultrasonic piezoelectric properties, improving upon the problems of insufficient electrical signal and signal collapse in existing ultrasonic piezoelectric materials. To enhance and expand the biological functions of this ultrasonic piezoelectric bilayer composite membrane, the invention also modifies its surface. Magnesium-containing compounds are adsorbed or a magnesium oxide layer is deposited on the surface of the bilayer membrane through physical adsorption. After surface modification, the composite material can degrade to produce magnesium ions (MgO) under physiological conditions. 2+ It promotes tissue repair. Furthermore, under ultrasound conditions, the electrical stimulation generated by the composite material can also activate magnesium ion channels, synergistically promoting nerve, blood vessel, and bone regeneration. Therefore, this ultrasound piezoelectric composite material possesses multiple biological functions and can be applied in periosteal repair, spinal cord injury repair, and traumatic brain injury repair.
[0016] The present invention employs a layer-by-layer manufacturing method for bilayer membranes, which can form an integrated bilayer composite membrane, reduce its anisotropy, and improve the mechanical properties of the composite membrane.
[0017] The composite material provided by this invention can synergistically enhance Mg through electrical stimulation generated by ultrasonic signals. 2+ Its biological functions.
[0018] The composite material provided by this invention can generate electrical stimulation in biological materials through non-invasive ultrasound. Compared with the method of directly applying electrical stimulation, this invention is more convenient and the application method is more flexible and controllable in the tissue repair process. Attached Figure Description
[0019] Figure 1 This is a schematic diagram illustrating the preparation process and application of the ultrasonic piezoelectric composite material in Example 1 of the present invention.
[0020] Figure 2 This is a scanning electron microscope image of the ultrasonic piezoelectric composite material in Embodiment 1 of the present invention.
[0021] Figure 3 This is a graph showing the tensile properties test results of the ultrasonic piezoelectric composite material in Example 1 of the present invention.
[0022] Figure 4This is a graph showing the test results of the ultrasonic piezoelectric properties of the ultrasonic piezoelectric composite material in Example 1 of the present invention.
[0023] Figure 5 This is a graph showing the biosafety performance test results of the ultrasonic piezoelectric composite material in Example 1 of the present invention.
[0024] Figure 6 These are live and dead staining images of different cells in the ultrasonic piezoelectric composite material of Example 1 of the present invention. Detailed Implementation
[0025] The following embodiments are merely some, not all, of the embodiments of the present invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.
[0026] In this invention, unless otherwise specified, all equipment and raw materials are commercially available or commonly used in the industry. The methods described in the following embodiments are conventional methods in the art, unless otherwise specified.
[0027] Example 1 In this embodiment, the specific parameters of the chemical reagents used are as follows: Polylactic acid: weight average molecular weight is 150,000.
[0028] Barium titanate (BTO): Tetragonal phase barium titanate nanoparticles with a particle size of 200~300 nm.
[0029] Magnesium-aluminum layered bimetallic hydroxides: sheet diameter 600~1000 nm; thickness 20~100 nm.
[0030] This embodiment provides an ultrasonic piezoelectric composite material, the preparation process of which is as follows: Figure 1 As shown, the specific steps include: (1) Preparation of bilayer BaTiO3 / PLLA composite membrane a) Preparation of electrospinning solution: At room temperature, 2.5 g of polylactic acid (PLLA) and 0.25 g of BaTiO3 were magnetically stirred and ultrasonically dissolved in 20 mL of hexafluoroisopropanol for 24 hours.
[0031] b) Preparation of BaTiO3 / PLLA disordered fiber spun membrane: Take 8 mL of the above electrospinning solution and place it in the nozzle device for electrospinning. The electrospinning parameters are: constant flow rate of 0.8 mL / h, fixed distance between the spinneret and the receiving device of 12~13 cm, adjust the high voltage power supply, set the positive voltage to 16 kV and the negative voltage to -2.5 kV, and adjust the rotation speed of the receiving device to 500 rpm to obtain the disordered fiber spun membrane.
[0032] c) Composite BaTiO3 / PLLA ordered fiber spun membrane: Place the remaining 12 mL of electrospinning solution in the nozzle device and continue electrospinning on the disordered fiber spun membrane. The electrospinning parameters are: constant flow rate of 0.8 mL / h, fixed distance from the spinneret to the receiving device of 12~13 cm, rotation speed of the receiving device of 3000 rpm, positive pressure of 30 kV and negative pressure of -14 kV. After spinning, the ordered fiber spun membrane can be composited on the disordered fiber spun membrane to obtain a double-layer BaTiO3 / PLLA composite membrane (BTO / PLLA composite membrane).
[0033] (2) Surface-active modification a) Magnesium chloride hexahydrate (0.06 mol, 3.66 g), aluminum chloride hexahydrate (0.03 mol, 2.16 g), and urea (3.78 g) were dissolved in deionized water, and the mixture was sonicated and stirred for 3 hours. Subsequently, the mixed solution was transferred to a polytetrafluoroethylene-lined stainless steel high-pressure reactor and reacted at 160°C for 12 hours. The product was collected by centrifugation, washed repeatedly with deionized water to remove residual ions, and finally freeze-dried to obtain magnesium-aluminum layered bimetallic hydroxides (MgAl-LDHs). b) Preparation of MgAl-LDHs aqueous solution: At room temperature, 0.4 g MgAl-LDHs were placed in 40 mL of ultrapure water and magnetically stirred for 24 hours.
[0034] c) MgAl-LDHs surface loading: The bilayer membrane prepared in step (1) was placed in an aqueous solution of MgAl-LDHs and stirred at 70 rpm for 24 hours at room temperature so that MgAl-LDHs were uniformly adsorbed on the surface of the bilayer BaTiO3 / PLLA composite membrane.
[0035] d) Remove the composite membrane, wash it three times with high-purity water, and let it stand for 30 minutes after each wash. Then dry it in a vacuum drying oven to obtain the ultrasonic piezoelectric composite material (BTO / PLLA@LDH).
[0036] In this embodiment, a bilayer composite membrane (PLLA composite membrane) was also prepared using the above method with an electrospinning solution that does not contain barium titanate. Scanning electron microscope images of the PLLA composite membrane, BTO / PLLA composite membrane, and BTO / PLLA@LDH bilayer membrane structures are shown below. Figure 2 As can be seen from the figure, the composite membrane exhibits a bilayer structure, with an ordered upper layer of approximately 100-200 μm in thickness and a disordered lower layer of approximately 100-200 μm in thickness.
[0037] In this embodiment, BTO / PLLA composite membranes with bilayer structures were also prepared using electrospinning solutions with other ratios, as shown in Table 1: Table 1
[0038] In Table 1, the 10% in 10%BTO / PLLA means that the mass of BTO is 10% of the mass of PLLA, and the same applies to the others. In the following text, unless otherwise specified, BTO / PLLA refers to 10%BTO / PLLA.
[0039] The tensile properties test results of the composite membrane prepared in this embodiment are shown in the figure. Figure 3 As can be seen from the figure, the composite film can maintain good tensile strength when the BTO content is 0-20%.
[0040] In this embodiment, the ultrasonic piezoelectric properties of the composite membrane were tested, and the test results are shown in [the table below]. Figure 4 In the figure: disordered PLLA is a barium titanate-free disordered fiber spun film prepared by the above electrospinning process; ordered PLLA is a barium titanate-free ordered fiber spun film prepared by the above electrospinning process; ordered 10% BTO / PLLA, ordered 20% BTO / PLLA, and ordered 30% BTO / PLLA are ordered fiber spun films prepared by the above electrospinning process according to the ratios in Table 1; 20% BTO / PLLA is a bilayer composite film prepared by electrospinning according to the ratios in Table 1; 20% BTO / PLLA is a bilayer composite film prepared by electrospinning according to the ratios in Table 1 and subsequent steps, and loaded with MgAl-LDH. As can be seen from the figure, the piezoelectric properties of the BTO-containing composite film are significantly improved, and loading MgAl-LDH nanomaterials on the surface of the bilayer film can enhance the piezoelectric effect.
[0041] This embodiment tested the biosafety performance of the composite membrane, and the test results are shown below. Figure 5In the figure: PLLA represents a bilayer composite membrane prepared using an electrospinning solution without barium titanate; 10% BTO / PLLA, 20% BTO / PLLA, and 30% BTO / PLLA represent bilayer composite membranes prepared by electrospinning according to the ratios in Table 1; 20% BTO / PLLA@LDH represents a bilayer composite membrane prepared by electrospinning according to the ratios in Table 1 and loaded with MgAl-LDH. As can be seen from the figure, the composite membranes prepared according to the above method with different ratios all exhibit good biocompatibility, and the bilayer composite membrane loaded with MgAl-LDH can further improve cell compatibility.
[0042] Figure 6 The image shows different cells subjected to ultrasound treatment (1W / cm²) on the aforementioned PLLA bilayer composite membrane and 10% BTO / PLLA@LDH. 2 Cell viability staining results under conditions of ultrasound treatment (5 minutes) and without ultrasound treatment. The figures show that different cells can grow normally on the composite membrane, and ultrasound treatment promotes cell adhesion and proliferation.
[0043] Example 2 like Figure 1 As shown, the composite membrane provided by this invention can be used for periosteal repair, spinal cord injury, and traumatic brain injury. Its method of use includes the following steps: The composite membrane is first sterilized by irradiation, then surgically implanted into the damaged tissue site. After suturing the surgical site, the damaged site is treated with ultrasound weekly (ultrasound intensity 0.5-2 W / cm). 2 The time is 1-10 minutes, preferably 1W / cm. 2 (5 minutes) to generate electrical stimulation, thereby promoting tissue repair at the damaged site.
[0044] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. An ultrasonic piezoelectric composite material, characterized in that, The film includes a first thin film layer and a second thin film layer stacked together; the first thin film layer and the second thin film layer are made of a polymer doped with barium titanate; the first thin film layer is a disordered fiber spun film and the second thin film layer is an ordered fiber spun film; the surface of the first thin film layer and / or the second thin film layer is further loaded with a magnesium-containing compound, or, the surface of the first thin film layer and / or the second thin film layer is deposited with a magnesium oxide layer.
2. The ultrasonic piezoelectric composite material according to claim 1, characterized in that, The polymer is selected from either polylactic acid or polycaprolactone; And / or, the barium titanate is tetragonal barium titanate nanoparticles; And / or, the magnesium-containing nanocompound is selected from at least one of magnesium-aluminum layered bimetallic hydroxide, magnesium oxide nanoparticles, and polyphenol-modified MgO nanoparticles.
3. The ultrasonic piezoelectric composite material according to claim 2, characterized in that, The polylactic acid has a weight-average molecular weight of 100,000 to 300,000; the polycaprolactone has a weight-average molecular weight of 80,000 to 300,000. And / or, the barium titanate has a particle size of 100~350 nm; And / or, the sheet diameter of the magnesium-aluminum layered bimetallic hydroxide is 0.6 ~ 4 μm.
4. The ultrasonic piezoelectric composite material according to claim 1, characterized in that, In the first and / or second thin film layers, the mass ratio of barium titanate to polymer is 0.08 to 0.375:
1.
5. The ultrasonic piezoelectric composite material according to claim 1, characterized in that, The thickness ratio of the first thin film layer to the second thin film layer is 0.5 to 2:1; And / or, the thickness ratio of the first thin film layer to the deposited magnesium oxide layer is 1000~4000:1; And / or, in the second thin film layer, the fiber orientation is perpendicular to the thickness direction of the second thin film layer.
6. The method for preparing the ultrasonic piezoelectric composite material according to any one of claims 1-5, characterized in that, Includes the following steps: (1) A disordered first thin film layer was prepared by electrospinning using a polymer solution containing barium titanate; An ordered second thin film layer was prepared on the first thin film layer by electrospinning using a polymer solution containing barium titanate; The polymer solution contains barium titanate; Alternatively, an ordered second thin film layer can be prepared by electrospinning using a polymer solution containing barium titanate; A disordered first thin film layer was prepared on the second thin film layer by electrospinning using a polymer solution containing barium titanate. The polymer solution contains barium titanate; (2) Immerse the product of step (1) in a magnesium compound solution, or deposit a magnesium oxide layer on the first thin film layer and / or the second thin film layer.
7. The preparation method according to claim 6, characterized in that, The solvent of the polymer solution is selected from at least one of hexafluoroisopropanol, dichloromethane, and trichloromethane.
8. The preparation method according to claim 6, characterized in that, The process parameters for preparing the disordered first thin film layer by electrospinning are as follows: The flow rate of the spinning solution is constant, ranging from 0.8 to 1 mL / h; The distance between the spinneret and the receiving device is 12-13 cm; Positive voltage is 16~20 kV, negative voltage is -2.5~-2 kV; The receiving device rotates at 500~800 rpm.
9. The preparation method according to claim 6, characterized in that, The process parameters for preparing an ordered second thin film layer by electrospinning are as follows: The flow rate of the spinning solution is constant, ranging from 0.8 to 1 mL / h; The distance between the spinneret and the receiving device is 12-13 cm; Positive voltage is 30~35 kV, negative voltage is -14~-10 kV; The receiving device rotates at 3000~6000 rpm.
10. The preparation method according to claim 6, characterized in that, In step (2), the total mass ratio of the first thin film layer and the second thin film layer to the mass ratio of the magnesium-containing compound is 6~9:1.