Preparation method of ultrasonic response nano-composite piezoelectric film

Abstract

The invention belongs to the field of biomedical materials, and provides a preparation method of an ultrasonic response nano composite piezoelectric film, which comprises the following steps: preparation of a KNN nanowire precursor, preparation of a KNN nanowire, preparation of a KNN (at) PDA nanowire, preparation of a PCL / KNN (at) PDA solution and preparation of a PCL / KNN (at) PDA film. According to the preparation method, the piezoelectric film is prepared by using the polycaprolactone and the KNN nanowire which are relatively good in biocompatibility and degradability, so that the risk of a secondary operation is avoided; through the PCL / KNN (at) PDA film, regulation and control of electric energy output by adjusting external ultrasonic pulses are realized; the PDA is modified on the surface of the KNN nanowire, so that the aggregation problem in a PCL matrix is avoided.

Description

Technical Field

[0001] The invention relates to the field of biomedical materials, and in particular to a method for preparing an ultrasonically responsive nanocomposite piezoelectric film. Background Art

[0002] The number of patients with diabetes is increasing worldwide, and this metabolic disease poses a major obstacle to tissue repair. Studies have shown that the delay or failure of diabetes-related bone regeneration is mainly due to the chronic excessive inflammatory state throughout the healing process, especially the abnormally slow or even stagnant transition from pro-inflammatory macrophages to anti-inflammatory macrophages. This situation leads to the failure of key downstream cell behaviors required for tissue regeneration, including stem cell homing, angiogenesis, and osteogenic differentiation, to occur in an orderly manner, thereby hindering the process of diabetic bone repair. These problems indicate that the development of biomaterials and strategies for diabetic bone repair is urgently needed. Physiological electrical signals play an indispensable role in maintaining tissue homeostasis. Repairing tissue defects through exogenous electrical stimulation or electrical microenvironment has achieved remarkable medical effects. Studies have confirmed that generating electrical signals at physiological levels through implanted membranes can effectively accelerate bone healing.

[0003] Because electrical stimulation devices may cause potential damage, such as the risk of infection with wired electrical stimulation devices. At the same time, the non-degradability of the material requires a secondary operation to remove the electrode interface, which will increase the user's expenses and cause more physical damage to the user. Summary of the invention

[0004] In order to overcome the shortcomings of the prior art, the purpose of the present invention is to provide a method for preparing an ultrasonically responsive nanocomposite piezoelectric film, by using polycaprolactone and KNN nanowires with good biocompatibility and degradability to prepare the piezoelectric film, thereby avoiding the risk of secondary surgery; by using PCL / KNN@PDA film to achieve regulation of electrical energy output by adjusting external ultrasonic pulses; by modifying PDA on the surface of KNN nanowires, the aggregation problem in the PCL matrix is ​​avoided.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] A method for preparing an ultrasonically responsive nanocomposite piezoelectric film, comprising:

[0007] 37.275 g of potassium chloride powder, 3.45 g of potassium carbonate powder and 13.29 g of niobium pentoxide powder were mixed and ground, and calcined at 1000° C. for 3 hours. The calcined product powder was soaked in a nitric acid solution for 48 hours. The product obtained after the soaking was washed and dried at 60° C. for 12 hours to obtain a KNN nanowire precursor.

[0008] 3.35 g of sodium carbonate powder, 0.3 g of sodium chloride powder, 3.35 g of potassium chloride, 0.34 g of potassium carbonate and 1 g of the KNN nanowire precursor were calcined at 850° C. for 10 minutes, and then washed, centrifuged and dried at 60° C. for 12 hours to obtain KNN nanowires;

[0009] 1 g of the KNN nanowires were dissolved in 200 ml of Tris-HCl buffer and subjected to ultrasonic treatment for 1 hour to obtain a first mixed solution, and 0.1 g of dopamine hydrochloride powder was added to the first mixed solution, followed by stirring for 12 hours and centrifugation to obtain KNN@PDA nanowires;

[0010] Ultrasonic dispersion of the KNN@PDA nanowires in hexafluoroisopropanol to obtain a second mixed solution, and adding polycaprolactone powder to the second mixed solution and stirring to obtain a PCL / KNN@PDA solution;

[0011] The PCL / KNN@PDA solution was subjected to film preparation by an electrospinning method to obtain a PCL / KNN@PDA film.

[0012] Preferably, the width of the KNN@PDA nanowire is 350 nm.

[0013] Preferably, the mass fraction of the KNN@PDA nanowires in the PCL / KNN@PDA film is 10wt%.

[0014] Preferably, it also includes:

[0015] Performing a gold electrode coating treatment on the PCL / KNN@PDA film to obtain a thin film electrode;

[0016] Connecting a copper wire to the thin film electrode to obtain a PCL / KNN@PDA film nanogenerator;

[0017] The PCL / KNN@PDA membrane nanogenerator is attached with a polydimethylsiloxane film to obtain a PCL / KNN@PDA membrane nanoinsulating generator.

[0018] The present invention discloses the following technical effects:

[0019] The present invention provides a method for preparing an ultrasonically responsive nanocomposite piezoelectric film. By using polycaprolactone and KNN nanowires, the risk of secondary surgery of traditional equipment is solved, and the preparation of piezoelectric films with better biocompatibility and degradability is achieved. By using PCL / KNN@PDA film, the defect of single power output of traditional equipment is solved, and the power output is regulated by adjusting external ultrasonic pulses. By modifying PDA on the surface of KNN nanowires, the aggregation problem in the traditional PCL matrix is ​​solved, and the stable preparation of PCL / KNN@PDA film is achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0021] Figure 1 A schematic diagram of the preparation process of an ultrasonic responsive nanocomposite piezoelectric film provided in an embodiment of the present invention;

[0022] Figure 2 A scanning electron microscope image of a 10 wt% PCL / KNN@PDA film provided in an embodiment of the present invention;

[0023] Figure 3 A scanning electron microscope image of a 20wt% PCL / KNN@PDA film provided in an embodiment of the present invention;

[0024] Figure 4 A scanning electron microscope image of a 30wt% PCL / KNN@PDA film provided in an embodiment of the present invention;

[0025] Figure 5 A simulation diagram of the open circuit voltage generated by the PCL / KNN@PDA film provided in an embodiment of the present invention under ultrasonic excitation;

[0026] Figure 6 A simulation diagram of the short-circuit current generated by the PCL / KNN@PDA film provided in an embodiment of the present invention under ultrasonic excitation;

[0027] Figure 7 A simulation diagram of the voltage output by the PCL / KNN@PDA film nano-insulation generator under ultrasonic excitation provided by an embodiment of the present invention;

[0028] Figure 8 A simulation diagram of the current output by the PCL / KNN@PDA film nano-insulation generator under ultrasonic excitation provided by an embodiment of the present invention;

[0029] Fig. 9 The statistical graph of the macrophage CCK8 cell activity experiment after the PCL / KNN@PDA membrane nano-insulated generator provided in the embodiment of the present invention was co-cultured with macrophages for 1, 3, and 5 days;

[0030] Fig.10 The PCL / KNN@PDA membrane nano-insulated generator provided in the embodiment of the present invention is co-cultured with macrophages and subjected to different doses of ultrasound stimulation for 1, 3, and 5 days before the macrophage CCK8 cell activity experiment statistical chart;

[0031] Fig.11 Representative micro-CT images and quantitative analysis bar graphs of skull defect samples of rats at 4 weeks and 8 weeks after skull defect provided in the embodiments of the present invention. DETAILED DESCRIPTION

[0032] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] The purpose of the present invention is to provide a method for preparing an ultrasonically responsive nanocomposite piezoelectric film, by using polycaprolactone and KNN nanowires with good biocompatibility and degradability to prepare the piezoelectric film, thereby avoiding the risk of secondary surgery; by using PCL / KNN@PDA film to achieve regulation of electrical energy output by adjusting external ultrasonic pulses; by modifying PDA on the surface of KNN nanowires, the aggregation problem in the PCL matrix is ​​avoided.

[0034] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0035] Figure 1 A schematic diagram of the preparation process of the ultrasonic responsive nanocomposite piezoelectric film provided in an embodiment of the present invention is shown in FIG. Figure 1 As shown, the present invention provides a method for preparing an ultrasonic responsive nanocomposite piezoelectric film, comprising:

[0036] Step 100: 37.275 g of potassium chloride powder, 3.45 g of potassium carbonate powder and 13.29 g of niobium pentoxide powder are mixed and ground, and calcined at 1000° C. for 3 hours. The calcined product powder is soaked in a nitric acid solution for 48 hours. The product obtained after the soaking is washed and dried at 60° C. for 12 hours to obtain a KNN nanowire precursor.

[0037] Step 200: calcining 3.35 g of sodium carbonate powder, 0.3 g of sodium chloride powder, 3.35 g of potassium chloride, 0.34 g of potassium carbonate and 1 g of the KNN nanowire precursor at 850° C. for 10 minutes, and sequentially washing, centrifuging and drying at 60° C. for 12 hours to obtain KNN nanowires;

[0038] Step 300: dissolving 1 g of the KNN nanowires in 200 ml of Tris-HCl buffer and subjecting the mixture to ultrasonic treatment for 1 hour to obtain a first mixed solution, and adding 0.1 g of dopamine hydrochloride powder to the first mixed solution, stirring the mixture for 12 hours and subjecting the mixture to centrifugation to obtain KNN@PDA nanowires;

[0039] Step 400: ultrasonically dispersing the KNN@PDA nanowires in hexafluoroisopropanol to obtain a second mixed solution, and adding polycaprolactone powder to the second mixed solution and stirring to obtain a PCL / KNN@PDA solution;

[0040] Step 500: Prepare a film from the PCL / KNN@PDA solution using an electrospinning method to obtain a PCL / KNN@PDA film.

[0041] Preferably, the width of the KNN@PDA nanowire is 350 nm.

[0042] Preferably, the mass fraction of the KNN@PDA nanowires in the PCL / KNN@PDA film is 10wt%.

[0043] Furthermore, it also includes:

[0044] Performing a gold electrode coating treatment on the PCL / KNN@PDA film to obtain a thin film electrode;

[0045] Connecting a copper wire to the thin film electrode to obtain a PCL / KNN@PDA film nanogenerator;

[0046] The PCL / KNN@PDA membrane nanogenerator is attached with a polydimethylsiloxane film to obtain a PCL / KNN@PDA membrane nanoinsulating generator.

[0047] Specifically, this embodiment provides an ultrasonically responsive PCL / KNN@PDA film. The ultrasonically responsive nanocomposite piezoelectric film can regulate the output of electrical energy by adjusting the ultrasonic pulse. The piezoelectric composite film matrix is ​​polymer PCL, and the piezoelectric dopant is K0.5Na0.5NbO3 (KNN) nanowire. In order to solve the aggregation problem in the PCL matrix, the surface of the KNN nanowire is modified with a polydopamine (PDA) coating, and the width of the PDA-modified KNN nanowire (KNN@PDA) is about 350nm.

[0048] Preferably, the mass fraction of KNN@PDA nanowires in the PCL / KNN@PDA film is 10 wt %.

[0049] Furthermore, this embodiment designs a PCL / KNN@PDA membrane nano-insulated generator, which uses PCL / KNN@PDA film as the core component, gold foil as the conductive layer, copper wire as the electrode, and PDMS film as the encapsulation layer. The preparation steps are: Au electrode coating the PCL / KNN@PDA film, and then using Cu wire as the wire of the PCL / KNN@PDA nano-generator. Finally, a polydimethylsiloxane (PDMS) film is used to insulate and protect the PCL / KNN@PDA nano-generator. The PCL / KNN@PDA membrane nano-insulated generator can be used in the bone defect repair process.

[0050] Specifically, the test results of the structure and performance of the ultrasonic responsive nanocomposite piezoelectric film are as follows:

[0051] refer to Figure 2 ,from Figure 2 It can be determined that the 10wt% PCL / KNN@PDA film prepared in this example has a compact, continuous and smooth fiber structure, and there are small pores of about 5-10μm between the fibers.

[0052] refer to Figure 3 and Figure 4 ,from Figure 3 and Figure 4 It can be determined that further increasing the addition amount of KNN@PDA (20–30wt%) will lead to severe aggregation and breakage of PCL fibers.

[0053] Furthermore, typical ultrasound parameters were selected, including an ultrasound frequency of 100 kHz, a pulse width of 50 μs, a pulse interval of 10 ms, and a power of 0.7 W / cm 2 The power intensity was tested underwater to test the electrical output capacity under ultrasonic stimulation.

[0054] from Figure 5 and Figure 6 It can be seen that the open circuit voltage and short circuit current of the 10wt% PCL / KNN@PDA film can reach 4.4V and 20μA, respectively, indicating that it can output electrical signals excited by ultrasound.

[0055] from Figure 7 and Figure 8 It can be seen that the voltage and current output by the piezoelectric film nanogenerator designed in this embodiment are both sinusoidal waves, and the signal interval is about 10-5s, indicating its real-time response to ultrasonic vibration.

[0056] Specifically, biocompatibility testing:

[0057] from Fig. 9 It can be seen that the 10wt% PCL / KNN@PDA film has excellent biocompatibility and no obvious cytotoxicity.

[0058] from Fig.10 It can be seen that the application of membrane nanogenerators and two types of ultrasound-driven electrical stimulation has no harmful effects on cell survival and is biosafe.

[0059] Furthermore, in vivo osteogenic performance under diabetic conditions:

[0060] Sprague-Dawley (SD) rats aged 6 to 8 weeks were used to establish a type 2 diabetes model and create skull defects. The SD rats were fed a high-fat diet for 4 weeks and injected with 30 mg / kg of streptozotocin. The fasting blood glucose level was stable at more than 11 mmol / L for more than 2 weeks, which was considered a successful diabetes model. After anesthesia and disinfection, a sagittal incision was made along the rat scalp to expose the bilateral skull. Then, a 5 mm diameter drill was used to create two parallel circular defects on both sides of the rat skull. The defects on both sides were covered with PCL / KNN@PDA membrane nano-insulated generators. In the first 3 weeks, the rats received low-dose (L-US, 10 minutes) or high-dose (H-US, 30 minutes) ultrasound-driven (100 kHz, 100 KPa sound pressure) radio stimulation treatment on both sides of the skull defects, where the L-US / H-US combination strategy was L-US in the first week and H-US in weeks 2-3. The skull specimens of SD rats were removed after 4 and 8 weeks for further analysis. From Fig.11 It can be seen that various ultrasound treatment methods based on PCL / KNN@PDA membrane nano-insulating generators can promote osteogenesis to a certain extent, among which the L-US / H-US combined strategy has the most significant effect on promoting new bone formation in diabetic rats after 4 and 8 weeks.

[0061] The beneficial effects of the present invention are as follows:

[0062] The present invention prepares the piezoelectric film by using polycaprolactone and KNN nanowires with good biocompatibility and degradability, thereby avoiding the risk of secondary surgery; the PCL / KNN@PDA film is used to achieve the regulation of electrical energy output by adjusting external ultrasonic pulses; and the aggregation problem in the PCL matrix is ​​avoided by modifying PDA on the surface of KNN nanowires.

[0063] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0064] The principles and implementation methods of the present invention are described in this article using specific examples. The description of the above embodiments is only used to help understand the method and core idea of ​​the present invention. At the same time, for those skilled in the art, according to the idea of ​​the present invention, there will be changes in the specific implementation methods and application scope. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A method for preparing an ultrasonically responsive nanocomposite piezoelectric film, characterized in that: include: 37.275 g of potassium chloride powder, 3.45 g of potassium carbonate powder and 13.29 g of niobium pentoxide powder were mixed and ground, and calcined at 1000° C. for 3 hours. The calcined product powder was soaked in a nitric acid solution for 48 hours. The product obtained after the soaking was washed and dried at 60° C. for 12 hours to obtain a KNN nanowire precursor. 3.35 g of sodium carbonate powder, 0.3 g of sodium chloride powder, 3.35 g of potassium chloride, 0.34 g of potassium carbonate and 1 g of the KNN nanowire precursor were calcined at 850° C. for 10 minutes, and then washed, centrifuged and dried at 60° C. for 12 hours to obtain KNN nanowires; 1 g of the KNN nanowires were dissolved in 200 ml of Tris-HCl buffer and subjected to ultrasonic treatment for 1 hour to obtain a first mixed solution, and 0.1 g of dopamine hydrochloride powder was added to the first mixed solution, followed by stirring for 12 hours and centrifugation to obtain KNN@PDA nanowires; Ultrasonic dispersion of the KNN@PDA nanowires in hexafluoroisopropanol to obtain a second mixed solution, and adding polycaprolactone powder to the second mixed solution and stirring to obtain a PCL / KNN@PDA solution; The PCL / KNN@PDA solution was subjected to film preparation by an electrospinning method to obtain a PCL / KNN@PDA film.

2. The method for preparing an ultrasonic responsive nanocomposite piezoelectric film according to claim 1, characterized in that: The width of the KNN@PDA nanowire is 350 nm.

3. The method for preparing an ultrasonic responsive nanocomposite piezoelectric film according to claim 1, characterized in that: The mass fraction of the KNN@PDA nanowires in the PCL / KNN@PDA film is 10 wt %.

4. The method for preparing an ultrasonically responsive nanocomposite piezoelectric film according to claim 1, characterized in that: Also includes: Performing a gold electrode coating treatment on the PCL / KNN@PDA film to obtain a thin film electrode; Connecting a copper wire to the thin film electrode to obtain a PCL / KNN@PDA film nanogenerator; The PCL / KNN@PDA membrane nanogenerator is attached with a polydimethylsiloxane film to obtain a PCL / KNN@PDA membrane nanoinsulating generator.

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