Antibacterial and repair-promoting piezoelectric film, and preparation method and application thereof

Abstract

This invention provides an antibacterial and repair-promoting piezoelectric film, its preparation method, and its application, belonging to the field of piezoelectric material technology. The method involves in-situ self-assembly of Fe-MOF on the surface of BTO, followed by further loading with DHA to synthesize an electrically controlled drug-release, antibacterial, and repair-promoting nanocomposite, BTO / Fe-MOF / DHA. BTO / Fe-MOF / DHA is then added to the surface of semi-cured PDMS to form an antibacterial and repair-promoting piezoelectric film, PDMS-BTO / Fe-MOF / DHA. When the PDMS-BTO / Fe-MOF / DHA piezoelectric film is subjected to ultrasonic stimulation, BTO converts mechanical energy into electrical energy, releasing Fe from the Fe-MOF... 3+ Reduced to Fe 2+ Fe-MOF degrades and releases DHA, and ultimately, Fe... 2+ Reacting with synchronously released DHA, it produces a large amount of toxic ROS, which damages proteins and nucleic acids, inducing bacterial death. The antibacterial and repair-promoting piezoelectric membrane of the present invention generates a piezoelectric potential during mechanical deformation caused by animal movement and induces EF at the wound site to promote wound healing. This antibacterial and repair-promoting piezoelectric membrane shows great potential in the future treatment of bacterial infected wounds.

Description

Technical Field

[0001] This invention belongs to the field of piezoelectric materials technology, specifically relating to an antibacterial and repair-promoting piezoelectric film, its preparation method, and its application. Background Technology

[0002] The skin, the largest organ in the human body, plays a vital role in regulating body temperature, protecting internal organs from external physical and chemical damage, and providing a physical barrier against pathogens and microorganisms. However, due to direct contact with the external environment, skin tissue has become one of the most vulnerable tissues. Every year globally, skin damage caused by various accidents or disease complications can lead to the loss of important barrier and sensory functions, and create an active gateway for infection at the wound site. Therefore, skin tissue is also an organ that is extremely susceptible to damage and bacterial infection.

[0003] Wound healing is a complex process, often accompanied by the risk of bacterial infection. On-demand wound treatment is essential to accelerate healing. Due to the complexity of the wound healing process, wound treatment has significant social and economic implications at individual, healthcare, and policymaker levels. Generally, wound healing comprises four distinct phases: hemostasis, inflammation, proliferation, and skin remodeling. These phases involve complex and coordinated interactions between various growth factors and cell types. However, the wound repair process often fails to follow these four phases perfectly, frequently due to disruption of multiple biological pathways and inflammatory responses caused by bacterial infection.

[0004] Antibiotics are often used as the main antibacterial material, and antibiotic-loaded wound dressings have a good bactericidal and therapeutic effect. However, in recent years, the overuse of antibiotics has accelerated the development of bacterial resistance, making single antibiotic-loaded wound dressings unable to effectively treat wound infections.

[0005] To combat bacterial infections and optimize wound healing, many nanomaterials and physical signal stimulation therapies are being used as antibacterial alternatives for wound healing management. These include nanoparticles such as silver, manganese dioxide, and titanium dioxide, as well as physical signal stimulation such as electrical stimulation, ultrasound stimulation, thermal stimulation, and exogenous magnetic fields. Among these strategies, electrical stimulation (ES) has attracted increasing attention due to its precise controllability and ability to accelerate the proliferation of endogenous cells at the skin wound site, thereby reducing wound healing time. In particular, ES has been shown to regulate cell proliferation and migration, reduce inflammation, and mimic or amplify potassium (K) levels. + ) and sodium (Na + The effect of ion-induced endogenous electric field on the wound can accelerate wound closure.

[0006] Materials capable of generating localized electrical stimulation fall into two categories: conductive materials and piezoelectric materials. Piezoelectric materials are non-conductive smart materials that reversibly undergo dimensional changes or structural deformations under mechanical stimulation, generating an electric potential in response to mechanical stress non-invasively. Therefore, against this backdrop, the concept of combining electrically stimulating wound dressings to actively stimulate the proliferation of endogenous cells at the wound site, reduce inflammation, and accelerate wound closure has attracted widespread attention from researchers.

[0007] Bhang et al. [1] Using zinc oxide nanorods as the piezoelectric layer, a piezoelectric electronic skin patch was developed that generates a piezoelectric potential through mechanical deformation and can be applied to skin wound sites. This patch can generate electrical stimulation to enhance endogenous cell metabolism, promote cell migration, and strengthen protein synthesis to promote wound healing. Wang et al. [2] By establishing a unique freeze-thaw-solvent substitution-annealing-swelling preparation process, an automated piezoelectric polyvinyl alcohol (PVA) / polyvinylidene fluoride (PVDF) composite hydrogel wound dressing was constructed. This piezoelectric hydrogel can convert the mechanical energy generated by the rat's body activity into electrical energy, providing real-time, uniform, and symmetrical local piezoelectric stimulation to promote wound healing. Although current research has achieved a series of results, relying solely on electrical stimulation as a repair treatment method is still insufficient to cope with severe infections, and single electrical stimulation is not enough to replace the effects of antibiotics.

[0008] Therefore, how to provide a superior repair material that can resist bacterial infection and promote wound healing has become an urgent technical problem to be solved.

[0009] The cited references are as follows:

[0010] [1]Bhang SH,Jang WS,Han J,et al.Zinc Oxide Nanorod-BasedPiezoelectric Dermal Patch for Wound Healing[J].Wiley-VCH Verlag,2017(1).DOI:10.1002 / adfm.201603497.

[0011] [2] Limin Wang, Yaru Yu, Xiaowen Zhao, Zhen Zhang, Xueling Yuan, Jinlong Cao, Weikun Meng, Lin Ye, Wei Lin, Guanglin Wang. Abiocompatible Self-Powered Piezoelectric Poly(vinyl alcohol)-Based Hydrogel for Diabetic Wound Repair[J]. ACS Applied Materials & Interfaces, 2022. Summary of the Invention

[0012] The present invention aims to solve the aforementioned technical problems by providing an antibacterial and wound-healing piezoelectric membrane, its preparation method, and its application. Compared with other antibacterial materials, the antibacterial and wound-healing piezoelectric membrane provided by the present invention exhibits superior antibacterial properties and wound-healing promotion performance.

[0013] One objective of this invention is to provide a method for preparing an antibacterial and repair-promoting piezoelectric film, comprising the following steps:

[0014] (1) Barium titanate nanoparticles were mixed with an ethanol solution containing mercaptoacetic acid and shaken to obtain carboxylated barium titanate nanoparticles.

[0015] (2) Carboxylated barium titanate nanoparticles were dispersed in an ethanol solution containing FeCl3, and then pyromellitic acid was added. The dispersion and self-assembly were carried out under heating, and the barium titanate-modified iron-based nanocomposite was obtained after centrifugation.

[0016] (3) The barium titanate modified iron-based nanocomposite was dispersed in a dihydroartemisinin solution and stirred to prepare a barium titanate modified iron-based nanocomposite loaded with dihydroartemisinin.

[0017] (4) Add barium titanate-modified iron-based nanocomposite loaded with dihydroartemisinin to the surface of semi-cured PDMS solution, and prepare the antibacterial and repair-promoting piezoelectric film by curing reaction.

[0018] This invention synthesizes an electrically controlled drug release nanocomposite (BTO / Fe-MOF / DHA) for antibacterial and repair-promoting effects by in-situ self-assembly of Fe-MOF on the surface of barium titanate (BTO) and further loading it with dihydroartemisinin (DHA). This BTO / Fe-MOF / DHA nanocomposite is then added to the surface of semi-cured PDMS to form an antibacterial and repair-promoting piezoelectric film, PDMS-BTO / Fe-MOF / DHA. The antibacterial and repair-promoting piezoelectric film obtained by this invention has the following characteristics: when the PDMS-BTO / Fe-MOF / DHA piezoelectric film is subjected to ultrasonic stimulation, BTO converts mechanical energy into electrical energy, and the Fe in the Fe-MOF... 3+ Reduced to Fe 2+ Fe-MOF degrades and releases DHA, and ultimately, Fe... 2+ Reacting with synchronously released DHA, it produces a large amount of toxic ROS, damaging proteins and nucleic acids and inducing bacterial death. Therefore, the antibacterial and repair-promoting piezoelectric membrane PDMS-BTO / Fe-MOF / DHA of the present invention generates a piezoelectric potential during mechanical deformation caused by animal movement and induces EF at the wound site to promote wound healing. This characteristic determines that the antibacterial and repair-promoting piezoelectric membrane of the present invention can better combat bacterial infection and optimize wound treatment.

[0019] However, as described in the embodiments of the present invention, when PDMS-BTO / Fe-MOF is selected and ultrasound is applied, the antibacterial effect is poor and the effect of the present invention cannot be achieved.

[0020] Furthermore, the concentration of mercaptoacetic acid in the ethanol solution in step (1) is 0.29 mM.

[0021] Furthermore, the oscillation time described in step (1) is 24 hours.

[0022] Furthermore, the molar ratio of FeCl3 to pyromellitic acid in step (2) is 1:1.

[0023] Furthermore, the dispersion conditions described in step (2) are dispersion at 70°C for 30 minutes.

[0024] Furthermore, during the dispersed self-assembly in step (2), five cycles are performed.

[0025] Furthermore, the concentration of the dihydroartemisinin solution in step (3) is 1.6 g·L⁻¹. -1 .

[0026] Furthermore, the mass-to-volume ratio of the barium titanate-modified iron-based nanocomposite to the dihydroartemisinin solution in step (3) is 5:3 mg / mL.

[0027] The second objective of this invention is to provide an antibacterial and repair-promoting piezoelectric membrane, which is prepared by any of the methods described above.

[0028] A third objective of this invention is to provide the application of the aforementioned antibacterial and wound-healing piezoelectric membrane, specifically its application in the preparation of antibacterial and / or wound-healing-promoting materials.

[0029] The beneficial effects of this invention are as follows:

[0030] The antibacterial and wound-healing piezoelectric membrane of this invention generates a piezoelectric potential during mechanical deformation caused by animal movement, and induces an EF at the wound site to promote wound healing. This antibacterial and wound-healing piezoelectric membrane achieves electrically controlled drug release for antibacterial and wound-healing effects, resulting in excellent therapeutic efficacy and extremely significant bactericidal and wound-healing effects. Attached Figure Description

[0031] Figure 1 (A) is a schematic diagram of the synthesis of BTO / Fe-MOF / DHA; (B) is a schematic diagram of the synthesis of PDMS-BTO / Fe-MOF / DHA.

[0032] Figure 2 The results of live / dead cell staining of L929 after different treatments.

[0033] Figure 3 (A) shows photographs of Escherichia coli colonies after different treatments on an agar plate; (B) shows the statistical results of bacterial activity after treatment (A). Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of this invention clearer, the invention is described in detail below with reference to embodiments. It should be noted that the following embodiments are for explanation and illustration only and are not intended to limit the invention. Non-essential improvements and adjustments made by those skilled in the art based on the above description are still within the scope of protection of this invention.

[0035] The names and abbreviations of the raw materials used in the following examples are as follows:

[0036] BTO: Barium titanate, MAA: Mercaptoacetic acid, H3BTC: Tristyric acid, DHA: Dihydroartemisinin, PDMS: Polydimethylsiloxane, NPs: Nanoparticles, NCs: Nanocomposites, Fe-MOF: Iron-based metal-organic framework materials.

[0037] Example 1

[0038] I. Material Preparation

[0039] (1) Preparation of BTO / Fe-MOF core-shell nanomaterials

[0040] First, 0.1 g of barium titanate (BTO) nanoparticles (NPs) were added to 20 mL of ethanol solution containing mercaptoacetic acid (MAA, 0.29 mM) and shaken for 24 h. The nanoparticles were washed three times with ethanol and deionized water to obtain carboxylated barium titanate nanoparticles, denoted as BTO / COOH NPs, which were then vacuum dried at room temperature for 24 h.

[0041] In addition, BTO / COOH NPs (0.02 g) were dispersed in 5 ml FeCl3 ethanol solution (10 mM) for 15 min, and then dispersed in 5 ml trimesic acid (H3BTC) ethanol solution (10 mM) at 70 °C for 30 min. Between each step, the NPs were centrifuged to remove the supernatant. After 5 cycles, BTO / Fe-MOF nanocomposites (NCs) were obtained. (2) Preparation of drug-loaded BTO / Fe-MOF / DHA

[0042] Disperse 5 mg of BTO / Fe-MOF NCs in 3 mL of 1.6 g·L⁻¹ -1 In a dihydroartemisinin (DHA) ethanol solution, the mixture was stirred at room temperature for 4 hours. Subsequently, the solution was diluted at 0.1 mL / min. -1 6 mL of distilled water was injected at a rate of [missing value], and stirring was continued for 20 h until the solvent evaporated. After washing and drying, the resulting nanocomposite was named BTO / Fe-MOF / DHA NCs.

[0043] (3) Preparation of PDMS-BTO / Fe-MOF / DHA antibacterial and repair-promoting piezoelectric membrane

[0044] To obtain a homogeneous and transparent PDMS solution (1.2 g, curing agent ratio 10:1), electric stirring was performed at 1000 rpm for 30 minutes. Additionally, 10 mL of 4 mg / mL solution was added. -1 An ethanol solution of BTO / Fe-MOF / DHA NCs was added to the PDMS surface that had been pre-cured at 70°C for 15 minutes. Finally, after curing in an oven at 70°C for 4 hours, a PDMS-BTO / Fe-MOF / DHA antibacterial and repair-promoting piezoelectric film with a thickness of 500 μm was formed.

[0045] II. Performance Testing

[0046] (1) Cell experiments

[0047] L929 (1.25×10 4 cells / cm 2 The cells were seeded into experimental membranes in 24-well plates and cultured for 24 hours to study cell adhesion morphology. Additionally, the membranes were irradiated with US (ultrasound) at 1.5 W / cm². -2The irradiation was applied to the cells at 1 MHz, 50% duty cycle, and 1 min. Additionally, a calcein acetoxymethyl ester / PI kit was used to label live / dead cells. Cells were observed using an inverted fluorescence microscope (OLYMPUS IX83).

[0048] (2) Antibacterial test

[0049] Escherichia coli was cultured overnight at 37°C in Luria-Bertani (LB) medium, with a final density of 1×10⁻⁶. 8 CFU·mL -1 2×10 5 CFU·mL -1 Escherichia coli was diluted with PBS at pH 7.4 and incubated in 24-well plates.

[0050] Five groups of Escherichia coli suspensions were prepared and then subjected to the following different treatments: 1) blank control; 2) PDMS-BTO / Fe-MOF; 3) PDMS-BTO / Fe-MOF + US (1.5 W·cm⁻¹). -2 , 1MHz, 50% duty cycle, 5min); 4) PDMS-BTO / Fe-MOF / DHA; 5) PDMS-BTO / Fe-MOF / DHA+US (1.5W·cm -2 (1MHz, 50% duty cycle, 5min). After US irradiation, incubate at 37℃ for 8h, then coat the plate.

[0051] The formula for calculating bacterial survival rate is as follows:

[0052] Survival rate = C / C0 × 100%

[0053] In the formula, C is the average number of bacterial colonies after treatment, and C0 is the average number of bacterial colonies in the control experiment.

[0054] (III) Experimental Results

[0055] (1) Synthesis and characterization results of materials

[0056] Electronically controlled drug release NCs (BTO / Fe-MOF / DHA) with antibacterial and repair-promoting properties were synthesized by in-situ self-assembly of Fe-MOF on the BTO surface and further loading with DHA. Figure 1 (Part A). First, BTO NPs were immersed in an ethanol solution of MAA to obtain BTO / COOH. Furthermore, these NPs were repeatedly dispersed sequentially in an ethanol solution containing FeCl3 and H3BTC for in-situ self-assembly of Fe-MOF. Finally, DHA was loaded by immersing the BTO / Fe-MOF in a solution containing drug (DHA) for 24 hours.

[0057] The preparation process of the PDMS-BTO / Fe-MOF / DHA antibacterial and repair-promoting piezoelectric membrane is as follows: Figure 1 As shown in Part B. First, BTO / Fe-MOF / DHA was added to the surface of semi-cured PDMS, and then cured at 70°C. The composite material was named PDMS-BTO / Fe-MOF / DHA.

[0058] (2) Cell Experiment Results

[0059] Live / dead staining experiments showed that the antibacterial and repair-promoting piezoelectric film and US (1.5 W·cm) -2 (1MHz, 50% duty cycle, 1min) is safe for cells. Figure 2 ).

[0060] (3) Results of bacterial experiments

[0061] like Figure 3 As shown in sections A and B, PDMS-BTO, PDMS-BTO / Fe-MOF, and PDMS-BTO / Fe-MOF / DHA treatments did not damage E. coli. When PDMS-BTO and US were irradiated simultaneously (for 5 min), the survival rate of E. coli was only 66%, indicating that piezoelectric BTO NPs can generate toxic ROS under US irradiation, effectively killing bacteria.

[0062] When subjected to PDMS-BTO / Fe-MOF and US (5 min irradiation), the survival rate of E. coli was only 55%, indicating that the formation of heterostructure led to enhanced acoustic dynamics.

[0063] After further US irradiation (5 min) of the PDMS-BTO / Fe-MOF / DHA group, the toxic ROS and DHA produced by BTO reacted with Fe... 2+ The bactericidal effect of the toxic ROS produced by the combination is enhanced, and almost all bacteria are eliminated.

Claims

1. A method for preparing an antibacterial and repair-promoting piezoelectric film, characterized in that, The steps include: (1) mixing barium titanate nanoparticles with an ethanol solution containing mercaptoacetic acid and then shaking to obtain carboxylated barium titanate nanoparticles; (2) Carboxylated barium titanate nanoparticles were dispersed in an ethanol solution containing FeCl3, and then pyromellitic acid was added. The dispersion and self-assembly were carried out under heating, and the barium titanate-modified iron-based nanocomposite was obtained after centrifugation. (3) The barium titanate-modified iron-based nanocomposite was dispersed in a dihydroartemisinin solution and stirred to prepare a barium titanate-modified iron-based nanocomposite loaded with dihydroartemisinin; the concentration of the dihydroartemisinin solution was 1.6 g·L⁻¹. -1 The mass-to-volume ratio of the barium titanate-modified iron-based nanocomposite to the dihydroartemisinin solution is 5:3 mg / mL. (4) Add barium titanate-modified iron-based nanocomposite loaded with dihydroartemisinin to the surface of semi-cured PDMS solution, and prepare the antibacterial and repair-promoting piezoelectric film by curing reaction.

2. The preparation method according to claim 1, characterized in that, The concentration of thioglycolic acid in the ethanol solution in step (1) is 0.29 mM.

3. The preparation method according to claim 1, characterized in that, The oscillation time described in step (1) is 24 hours.

4. The preparation method according to claim 1, characterized in that, The molar ratio of FeCl3 to pyromellitic acid in step (2) is 1:

1.

5. The preparation method according to claim 1, characterized in that, The dispersion conditions described in step (2) are dispersion at 70°C for 30 minutes.

6. The preparation method according to claim 1, characterized in that, In step (2), the dispersion self-assembly is performed in 5 cycles.

7. An antibacterial and repair-promoting piezoelectric membrane, characterized in that, It is prepared by the method described in any one of claims 1-6.

8. The application of the antibacterial and repair-promoting piezoelectric membrane according to claim 7, characterized in that, It is used in the preparation of materials that are antibacterial and / or promote wound healing.

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