Preparation and application of piezoelectric enhanced antibacterial composite nano dressing

Abstract

The invention belongs to the technical field of nano dressings, and particularly relates to preparation and application of a piezoelectric enhanced antibacterial composite nano dressing. The preparation method comprises the following steps: by taking PVDF as a base material, doping a MoO3-x / ZnFe2O4 nano composite material, and then preparing a polyvinylidene fluoride fiber membrane through an SBS (Styrene Butadiene Styrene) method; and finally, dispersing the MZ in a PVDF spinning solution, and carrying out blowing spinning together to prepare the PVDF-coated MoO3-x / ZnFe2O4 nanofiber dressing. By constructing the Z-type heterojunction MZ nano composite material, the compounding efficiency of electrons and holes is reduced, the ROS generation capability is enhanced, and the photocatalytic capability of the P-coated MZ nano composite fiber dressing is improved; on the other hand, the activity of peroxidase (POD) is enhanced by the generation of the local heat effect, so that the generation of hydroxyl free radicals (. OH) is promoted; the CAT activity is improved through heat, more oxygen is promoted to participate in the photocatalytic reaction, then the photocatalytic performance is effectively improved, the P-coated MZ nano-composite fiber dressing obtains a better antibacterial effect, the photocatalytic activity is effectively improved, and then the obvious inactivation effect is generated on drug-resistant bacteria at wounds.

Description

Technical Field

[0001] The invention belongs to the technical field of nano dressings, and in particular relates to the preparation and application of a piezoelectric enhanced antibacterial composite nano dressing. Background Art

[0002] Chronic diabetic wounds are one of the complications of diabetes. The difficulty of wound healing is one of the characteristics of chronic diabetic wounds. It has become a health issue that the world is increasingly concerned about. Wound healing is divided into four stages in chronological order: hemostasis, inflammation, proliferation and remodeling. Diabetic wounds are affected by bacterial infection, abnormal angiogenesis, tissue hypoxia, etc., which can affect the wound healing process and lead to incomplete or delayed wound healing. Treatment methods such as surgical debridement and antibiotics are not effective. In recent years, wound dressings have gradually become a research hotspot for the treatment of chronic diabetic wounds, including nanofiber membranes, hydrogels, microneedle patches, etc. Among them, nanofiber membranes have a greater clinical transformation background due to their good biocompatibility and processing properties.

[0003] There are many types of nanofiber membranes, including polyester lactone (PCL), thermoplastic polyurethane (TPU), polyacrylonitrile (PAN), polylactic acid (PLA), etc. Under normal circumstances, these fibers do not have the ability to kill bacteria and bacteria. They are often co-spun with nanomaterials and drugs with antibacterial functions to have antibacterial effects. As a scaffold, nanofibers can isolate the wound from the surrounding microenvironment, and kill the bacteria infected in the wound through the antibacterial properties of the nanomaterials, thereby achieving the effect of antibacterial and healing wounds. Among the many fiber substrates, PVDF has attracted widespread attention from researchers due to its unique properties. Since PVDF is a piezoelectric material, when it is subjected to external mechanical force, it will depolarize and form an endogenous electric field, and produce reactive oxygen species (ROS) with strong cytotoxicity through the transmission and transfer of electrons, thereby achieving the effect of inactivating bacteria. Therefore, PVDF is an ideal wound dressing material.

[0004] With the booming development of precision medicine, more and more advanced treatment technologies have been widely used in clinical practice. Among the many treatment methods, phototherapy is considered to be one of the most promising strategies for the treatment of microbial infections due to its controllability, low toxicity, spatiotemporal selectivity, non-invasiveness, wide antibacterial spectrum, and low resistance to drug resistance. Phototherapy includes photodynamic therapy (PDT) and photothermal therapy (PTT). PDT relies on the production of ROS by photosensitizers under the excitation of a certain wavelength to exert antibacterial effects, but its effect is often limited by the penetration depth of the laser. PTT is not affected by the penetration depth, and the combination of the two can achieve a synergistic antibacterial effect. ROS and thermal energy can irreversibly damage the bases of bacterial genetic material DNA, thereby destroying the double-stranded structure of DNA, interfering with normal bacterial proliferation and physiological metabolism, leading to DNA damage, and effectively killing a variety of pathogens, such as Gram-positive bacteria, Gram-negative bacteria, fungi, viruses and parasites. In addition to phototherapy, chemodynamic therapy (CDT) is also an effective treatment strategy for inactivating microorganisms. Since its discovery in 2016, CDT has been widely used in the treatment of wound infections. However, photothermal therapy needs to reach a higher temperature to completely kill bacteria, which will damage healthy tissues near the infected area, and low temperature cannot completely kill bacteria. The introduction of CDT will serve as a supplement to PTT antibacterial therapy and enhance the antibacterial effect of low-temperature PTT. In summary, the construction of a synergistic antibacterial system combining CDT, PDT and PTT therapies will play an excellent antibacterial role and meet the treatment needs of diseases such as infections caused by bacteria. For this reason, the present invention proposes the preparation and application of a piezoelectric enhanced antibacterial composite nano-dressing. Summary of the invention

[0005] The purpose of the present invention is to provide a preparation and application of a piezoelectric enhanced antibacterial composite nano dressing, and an MZ nanocomposite material is proposed for the first time. By constructing a Z-type heterojunction, the recombination efficiency of electrons and holes is reduced, and the photocatalytic performance of the material is improved. The present invention prepares a P@MZ fiber dressing for the first time, and by doping the MZ nanocomposite material, the β phase of PVDF is improved, the piezoelectric performance of the P@MZ fiber dressing is enhanced, and the antibacterial performance of the P@MZ fiber dressing is improved.

[0006] The technical solution adopted by the present invention is as follows:

[0007] Step 1: Disperse molybdenum metal powder in ethanol solution and stir at room temperature before adding H 2 O 2 , a yellow solution was obtained, and then the solution was transferred to a polytetrafluoroethylene container, sealed in a stainless steel autoclave, reacted at 160 ° C for 12 h, cooled to room temperature, washed with ethanol and water three times respectively, and dried at 60 ° C in vacuum overnight to obtain MoO 3-x (M) powder;

[0008] Step 2: Disperse zinc chloride, ferric chloride hexahydrate, sodium citrate dihydrate, and sodium acetate in ethylene glycol in sequence, dissolve by ultrasonication to obtain a reddish brown mixed solution, and then transfer the solution to a polytetrafluoroethylene container, react at 200°C for 12 hours, and after cooling to room temperature, wash with ethanol and water for three times respectively, and dry at 60°C for 12 hours to obtain ZnFe 2 O 4 (Z) powder;

[0009] Step 3: Disperse the molybdenum metal powder in the ethanol solution and add H 2 O 2 , a yellow solution was obtained, and then Z powder was dispersed in the yellow solution, transferred to a polytetrafluoroethylene container after ultrasonic dispersion, sealed in a stainless steel autoclave, reacted at 160 ° C for 12 h, cooled to room temperature, washed with ethanol and water three times respectively, and dried at 60 ° C in vacuum overnight to obtain MoO 3-x / ZnFe 2 O 4 (MZ) nanocomposites;

[0010] Step 4: Dissolve the MZ nanomaterial in DMF, ultrasonicate for 30 min, then add PVDF powder, and stir magnetically at 42 °C for 12 h to prepare a PVDF spinning solution with uniform MZ dispersion; finally, use the solution jet spinning technology to obtain PVDF@MoO 3-x / ZnFe 2 O 4 (P@MZ) composite nanofiber membrane.

[0011] Preferably, the H used in step 1 and step 3 is 2 O 2 The concentration of the solution is 30%; in step 4, the specific parameters of the solution jet spinning technology are: needle specification: 23G, propulsion rate: 10mL / h, receiving roller speed: 500rpm, receiving distance: 30cm, wind pressure: 120MPa.

[0012] Application of a piezoelectric enhanced antibacterial composite nano dressing in the preparation of a dressing drug for treating external wounds of diabetic patients.

[0013] The technical effects achieved by the present invention are:

[0014] The present invention proposes an MZ nanocomposite material for the first time, and by constructing a Z-type heterojunction, the recombination efficiency of electrons and holes is reduced, and the photocatalytic performance of the material is improved; the present invention prepares a P@MZ fiber dressing for the first time, and by doping the MZ nanocomposite material, the β phase of PVDF is improved, the piezoelectric performance of the P@MZ fiber dressing is enhanced, and the antibacterial performance of the P@MZ fiber dressing is improved.

[0015] The present invention designs and develops a piezoelectrically enhanced and photocatalytic nanocomposite fiber dressing for antibacterial treatment. The present invention uses PVDF as a substrate and incorporates MoO 3-x / ZnFe 2 O 4 (MZ) nanocomposite material, and then PVDF fiber membrane was prepared by SBS method; finally, MZ was dispersed in PVDF spinning solution and co-spun to prepare PVDF@MoO 3-x / ZnFe 2 O 4 (P@MZ) nanofiber dressing. On the one hand, by constructing a Z-type heterojunction MZ nanocomposite, the recombination efficiency of electrons and holes is reduced, the ability to generate ROS is enhanced, and the photocatalytic ability of the P@MZ nanocomposite fiber dressing is improved; on the other hand, the generation of local thermal effect enhances the POD activity, thereby promoting the generation of OH; at the same time, heat increases the CAT activity, prompting more oxygen to participate in the photocatalytic reaction, thereby effectively improving the photocatalytic performance, so that the P@MZ nanocomposite fiber dressing obtains a better antibacterial effect. In addition, the loading of nanocomposite materials (MZ) can significantly improve the piezoelectricity of PVDF. Under the action of ultrasound, the free charges in the built-in electric field of PVDF will be transferred to the heterojunction interface, participating in the transmission of photogenerated electrons and holes, thereby effectively improving the photocatalytic activity, and then producing a significant inactivation effect on drug-resistant bacteria in the wound. In summary, the P@MZ nanocomposite fiber dressing will obtain antibacterial effects from multiple dimensions, which can significantly improve the antibacterial effect of diabetic wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1a M SEM images of nanomaterials;

[0017] Figure 1b XRD pattern of M nanomaterials;

[0018] Figure 2a SEM images of Z nanomaterials;

[0019] Figure 2b XRD pattern of Z nanomaterial;

[0020] Figure 3a SEM images of MZ nanocomposites;

[0021] Figure 3b Elemental mapping of MZ nanocomposites;

[0022] Figure 3c XRD patterns of MZ nanocomposites;

[0023] Figure 3d PL spectra of MZ nanocomposites;

[0024] Figure 3e MZ is generated in darkness and light 1 O 2 、 ESR spectrum of OH;

[0025] Figure 3f The band structure of MZ nanocomposites;

[0026] Figure 3g UV absorption spectra of TMB color reaction catalyzed by MZ under different material concentrations, temperatures, and pH conditions;

[0027] Figure 3h The O production of MZ under different material concentration and pH conditions 2 situation;

[0028] Figure 3i Photothermal spectrum of MZ changing with visible light power;

[0029] Figure 4a Fiber physical picture;

[0030] Figure 4b SEM images of PVDF and P@MZ fibers;

[0031] Figure 4c Photothermal performance map of nanofiber dressings;

[0032] Figure 4d XRD, FTIR, and DSC spectra of nanofiber dressings;

[0033] Figure 4e Piezoelectric current of nanofiber dressings;

[0034] Figure 5a Plate coating results of different groups and MRSA and MRD.E.coli treatments under different stimulation conditions;

[0035] Figure 5b According to the plate coating results, the corresponding MRSA and MRD.E.coli survival rate quantification graph (n=3);

[0036] Figure 5c SEM images of different groups and after treatment with MRSA and MRD.E.coli under different stimulation conditions;

[0037] Figure 6a Representative photos of skin wounds on days 0, 3, 7, and 12 after treatment in different groups;

[0038] Figure 6b Photos of plate spreads on days 3, 7 and 12 after treatment with different groups.

[0039] Figure 7It is the overall flow chart of the present invention. Figure 7 Molybdenum powders (molybdenum powder), H2O2 (hydrogen peroxide), ZnFe2O4 (zinc ferrite), MoO3-x / ZnFe2O4 (composite materials); PVDF (polyvinylidene fluoride), Mixed solution (mixed solution), Nanofiber receiving device (fiber receiving device), PVDF@MoO3-x / ZnFe2O4 (nanofiber dressing-P@MZ); US (ultrasound), Light (irradiation). DETAILED DESCRIPTION

[0040] In order to make the purpose and advantages of the present invention more clearly understood, the present invention is specifically described below in conjunction with embodiments. It should be understood that the following text is only used to describe one or several specific embodiments of the present invention, and does not strictly limit the scope of protection of the specific claims of the present invention.

[0041] Embodiment 1:

[0042] like Figure 7 As shown, a method for preparing a composite nanomaterial comprises the following steps:

[0043] Step 1: MoO 3-x Preparation of (M):

[0044] 0.1919 g of molybdenum metal powder was dispersed in 24 mL of ethanol solution and stirred at room temperature and then H 2 O 2 (3 mL, 30%) to obtain a yellow solution, which was then transferred to a 50 mL polytetrafluoroethylene container, sealed in a stainless steel autoclave, reacted at 160 ° C for 12 h, cooled to room temperature, washed with ethanol and water three times respectively, and dried at 60 ° C in vacuum overnight to obtain MoO 3-x (M) Powder.

[0045] MoO 3-x (M) Structural characterization:

[0046] Scanning electron microscope (SEM) images of M nanomaterials are shown in Figure 2. Figure 1a As shown, Figure 1a SEM spectrum of M nanomaterial, M is a flake nanomaterial. The crystal structure was verified by X-ray powder diffractometer (XRD) analysis. The results are as follows Figure 1b As shown, Figure 1b The XRD spectrum of M nanomaterials is consistent with that of JCPDS NO.5-0508MoO 3-x Correspondingly, it shows that MoO 3-x (M) was successfully prepared.

[0047] Step 2: ZnFe 2 O 4 Preparation of (Z):

[0048] 0.164 g zinc chloride, 0.649 g ferric chloride hexahydrate, 0.240 g sodium citrate dihydrate, and 1.2 g sodium acetate were dispersed in 20 mL ethylene glycol in sequence, and a reddish brown mixed solution was obtained after ultrasonic dissolution. The solution was then transferred to a 50 mL polytetrafluoroethylene container, reacted at 200 ° C for 12 h, cooled to room temperature, washed with ethanol and water for 3 times respectively, and dried at 60 ° C for 12 h to obtain ZnFe 2 O 4 (Z) Powder.

[0049] ZnFe 2 O 4 (Z) Structural characterization:

[0050] SEM obtains the morphology of Z nanomaterials. Figure 2a As shown, Figure 2a SEM images of Z nanomaterials, the obtained ZnFe 2 O 4 (Z) is a spherical structure. XRD analysis verifies its crystal structure. The results are as follows Figure 2b As shown, Figure 2b The XRD spectrum of Z nanomaterials is consistent with that of JCPDS22-1012ZnFe 2 O 4 Correspondingly, it means that Z was successfully prepared.

[0051] Step 3: MoO 3-x / ZnFe 2 O 4 (MZ) Preparation of nanocomposites:

[0052] 0.1919 g of molybdenum metal powder was dispersed in 24 mL of ethanol solution and stirred at room temperature and then H 2 O 2 (3mL, 30%) to obtain a yellow solution, and then 0.048g Z powder was dispersed in the above yellow solution, transferred to a 50mL polytetrafluoroethylene container after ultrasonic dispersion, sealed in a stainless steel autoclave, reacted at 160°C for 12h, cooled to room temperature, washed with ethanol and water for 3 times respectively, and dried in vacuum at 60°C overnight to obtain an MZ nanocomposite material.

[0053] MoO 3-x / ZnFe 2 O 4 Structural characterization of (MZ):

[0054] The SEM image of MZ is shown in Figure 3a As shown, Figure 3a SEM images of the MZ nanocomposite. Morphological observations show that the Z nanoparticles are tightly loaded on the M nanosheets. The corresponding element mapping images are shown in Figure 3b As shown, Figure 3b The elemental mapping of the MZ nanocomposite showed the presence of Mo, O, Fe, and Zn elements, and the results further verified the uniform distribution of Z on the M nanosheets. Figure 3c As shown in the XRD spectrum, the characteristic peaks of the composite material are consistent with those of the single-component nanomaterials, confirming the successful preparation of the MZ nanocomposite material.

[0055] MoO 3-x / ZnFe 2 O 4 Photocatalytic and photothermal properties of (MZ):

[0056] In order to evaluate whether the composite of the two materials can improve the photocatalytic performance of the nanomaterials, firstly, the photoluminescence (PL) spectroscopy was used to study the photogenerated charge separation ability of the nanocomposite material and the two single materials, e.g. Figure 3d As shown, Figure 3d PL spectrum of MZ nanocomposites. The fluorescence intensity of MZ nanocomposites is significantly lower than that of M and Z, indicating that the recombination efficiency of photogenerated electrons and holes is reduced, the photocatalytic ability is improved, and the heterojunction is successfully constructed. Secondly, the electron spin resonance spectrometer (ESR) is used to detect the types of ROS generated by MZ nanocomposites, such as Figure 3e As shown, Figure 3e MZ is produced in darkness and light respectively 1 O 2 , ·OH ESR spectrum, MZ in the dark 1 O 2 The production of singlet oxygen ( 1 O 2 ), Z and MZ can produce ·OH in the dark, which is due to the CDT performance of Z. Both can produce ·OH under light, and the ROS intensity generated by MZ is stronger than that of M and Z, which further verifies the successful construction of the heterojunction and significantly improves the photocatalytic ability.

[0057] In order to clarify the generation mechanism of the above ROS, the band gap and valence band of Z and M were tested respectively, and the conduction band was calculated, and then the band structure of MZ composite material was obtained, as shown in Figure 3f As shown, Figure 3f The band structure of MZ nanocomposite materials, Z and M can form a Z-type heterojunction.

[0058] The POD enzyme activity of MZ was preliminarily evaluated by TMB colorimetric method. Figure 3g As shown, Figure 3g The UV absorption spectrum of the MZ-catalyzed TMB color development reaction under different material concentrations, temperatures, and pH conditions shows that the POD enzyme activity has a certain concentration dependence, and the UV absorption value increases with increasing temperature, indicating that the POD enzyme activity is temperature-dependent. At the same time, the lower the pH, the better the enzyme activity.

[0059] The MoO was evaluated using a dissolved oxygen meter. 3-x / ZnFe 2 O 4 The CAT enzyme activity of (MZ) can be determined by Figure 3h As shown, Figure 3h The O production of MZ under different material concentration and pH conditions 2 As the material concentration increases, the amount of O 2 The more the enzyme activity is, the more it produces O 2 The ability to produce O at pH 5.5 and 6.5 respectively 2 The ability of CAT is strong, indicating that the CAT enzyme activity performs best under neutral pH conditions.

[0060] The photothermal performance of MZ was preliminarily evaluated, such as Figure 3i As shown, Figure 3i The photothermal spectrum of MZ with visible light power shows a certain dependence on visible light power. When the power reaches 1000W / m 2 When the material temperature reaches about 50℃.

[0061] Step 4: PVDF@MoO 3-x / ZnFe 2 O 4 Preparation of (P@MZ) nanocomposite fiber dressing

[0062] Weigh 0.216g of MZ nanomaterials and dissolve them in 10mL DMF (N,N-dimethylformamide), ultrasonicate for 30min, then add 2.4g of PVDF powder (polyvinylidene fluoride powder), and stir magnetically at 42℃ for 12h to prepare a PVDF spinning solution with uniform MZ dispersion. Finally, the obtained spinning solution was subjected to solution jet spinning technology to obtain a P@MZ composite nanofiber membrane.

[0063] (Specific parameters are: needle specification: 23G, propulsion rate: 10mL / h, receiving roller speed: 500rpm, receiving distance: 30cm, wind pressure: 120MPa)

[0064] PVDF@MoO 3-x / ZnFe 2 O 4 Structural characterization of (P@MZ) nanocomposite fiber dressing

[0065] Figure 4a This is a physical picture of PVDF and P@MZ fibers. The nanofibers provide a supporting platform for MZ, evenly fixing MZ on its surface and enhancing the photocatalytic and photothermal effects. Figure 4b The SEM images show the surface morphology of PVDF and P@MZ nanofibers. PVDF nanofibers present a uniform, continuous and smooth fiber structure. On the MZ-containing nanofiber membrane, MZ nanoparticles attached to the surface of the nanofibers can be clearly seen.

[0066] PVDF@MoO 3-x / ZnFe 2 O 4 (P@MZ) Performance characterization of nanocomposite fiber dressing:

[0067] The photothermal performance of P@MZ was evaluated, such as Figure 4c As shown, Figure 4c Photothermal performance spectrum of nanofiber dressing, after doping with MZ, power 1000W / cm 2 After 10 minutes of illumination, P@MZ can rise to about 45℃.

[0068] The β-phase content of PVDF and P@MZ was preliminarily evaluated. Figure 4d As shown, Figure 4d The XRD, FTIR, and DSC spectra of the nanofiber dressing and the XRD and FTIR images of P@MZ show that after doping with MZ, the peak intensity of the α phase of the P@MZ fiber membrane dressing decreased compared with PVDF, and the peak intensity of the β phase increased. In differential scanning calorimetry (DSC), PVDF showed a melting point peak at 168.64°C, while P@MZ showed a melting point peak at 170.64°C. This is because the melting point of the β phase is higher than that of the α phase. Due to the presence of MZ nanoparticles, the β phase content of the MZ@P fiber membrane is increased, resulting in the melting point of MZ@P being significantly higher than that of PVDF. This shows that doping with MZ can effectively improve the piezoelectric properties of PVDF. As shown in Table 1, the β-phase content of the PVDF fiber membrane prepared by SBS is 81.80%, and the β-phase content of the PVDF fiber membrane prepared in the first related literature is 48.00%. In comparison, the β-phase content of the PVDF fiber membrane prepared by us is 33.80% higher; in addition, the β-phase content of P@MZ is 93.95%, indicating that doping MZ can effectively improve the piezoelectric properties of PVDF.

[0069] The generation of piezoelectric current of P@MZ nanofiber dressing was preliminarily evaluated by electrochemical workstation, such as Figure 4e As shown, Figure 4eThe piezoelectric current of the nanofiber dressing undergoes an ultrasonic switching cycle every 40 seconds. It can be seen that no piezoelectric current is generated when no external ultrasound is applied. On the contrary, piezoelectric current is generated when a certain amount of external ultrasound is applied, which further illustrates the piezoelectric properties of the nanofiber dressing P@MZ.

[0070] Table 1 β-phase content of nanofiber dressing (n=3)

[0071]

[0072]

[0073] Embodiment 2:

[0074] Application of a piezoelectric enhanced antibacterial composite nano dressing in the preparation of a dressing drug for treating external wounds of diabetic patients.

[0075] PVDF@MoO 3 -x / ZnFe 2 O 4 Antibacterial properties of (P@MZ) nanocomposite fiber dressings:

[0076] The PVDF and PVDF@MoO 3-x (P@M), PVDF@Zn 2 FeO 4 The antibacterial properties of P@Z and P@ZM nanofibers. The flat coating method intuitively demonstrated the inactivation ability of P@MZ against drug-resistant Staphylococcus aureus (MRSA). Figure 5aAs shown in Fig. 2 and Fig. 3, in the dark, PBS (Blank), PVDF, and P@M have almost no ability to inactivate bacteria, while P@Z and P@MZ have a weak ability to kill bacteria, which comes from the CDT performance of Z. The Light+ice group shows that the ROS produced by different groups in the case of pure light has an inactivation effect on bacteria. MZ effectively improves the photocatalytic performance of nanocomposites by constructing a Z-type heterojunction. Therefore, P@MZ effectively increases the yield of ROS under light irradiation, and the inactivation effect on bacteria is further improved. The Light group further illustrates the effect of heat-promoted CDT. Compared with the Light+ice group, P@MZ has significantly improved its ability to kill bacteria under light. On the one hand, heat energy inhibits the growth of bacteria, and on the other hand, heat promotes the production of ROS. Under the synergistic effect of photocatalysis / photothermal, the antibacterial ability of P@MZ is significantly improved. Under the action of external ultrasound. Except for the PBS group, the other groups all had a certain antibacterial effect, which was due to the piezoelectric properties of PVDF. At the same time, since the doping of MZ improved the piezoelectricity of PVDF itself, the inactivation effect of P@MZ on bacteria was significantly improved; finally, under the dual stimulation of light and ultrasound, the inactivation effect of bacteria basically reached 99%, which is the antibacterial effect of piezoelectric enhanced nanocomposite fiber membrane dressing. Figure 5a And as shown in 5b: Figure 5a Plate coating results of different groups and MRSA and MRD.E.coli treatments under different stimulation conditions; Figure 5b Quantification graph of the survival rates of MRSA and MRD.E.coli according to the plate coating results (n=3).

[0077] Subsequently, the bacterial morphology of the two drug-resistant bacteria after incubation with the fiber membrane under different stimulation conditions was observed by scanning electron microscopy. Under dark conditions, only the bacteria incubated with P@MZ showed damage in morphology, while the bacteria in the PVDF group and the control group had smooth morphology and intact cell membranes; under visible light irradiation, whether it was after adding ice or removing the ice, the bacteria incubated with P@MZ showed varying degrees of wrinkles and ruptures in morphology, while the bacteria in the PVDF group and the control group had smooth morphology and intact cell membranes; under the action of simple ultrasound, in addition to the bacteria treated with the control group showing a smooth surface morphology, the bacteria incubated with PVDF and P@MZ showed varying degrees of wrinkles and ruptured cell membrane morphology; under the dual stimulation of light and ultrasound, the bacteria treated with P@MZ had the most serious cell membrane damage and volume shrinkage, which may be caused by excessive leakage of bacterial contents. Figure 5c As shown, Figure 5c SEM images of different groups and after treatment with MRSA and MRD.E.coli under different stimulation conditions.

[0078] PVDF@MoO 3-x / ZnFe 2 O 4 (P@MZ) Nanocomposite fiber dressing promotes wound healing in diabetic mice:

[0079] A full-thickness skin wound model was established to evaluate the promoting effects of P@MZ fiber membrane on wound healing, anti-inflammation, and angiogenesis in diabetic mice infected with Staphylococcus aureus.

[0080] The wound treatment methods were as follows. For the Control group, a breathable sealing film was applied; for the 3 groups, a 3M commercial dressing was applied; for the PVDF group, a sterile PVDF dressing was applied and then a 1M ultrasound therapy device was used for 10 minutes; for the P@MZ group, a sterile P@MZ dressing was applied and then a 1M ultrasound therapy device was used for 10 minutes; for the P@MZ+Light group, a sterile P@MZ+Ligh dressing was applied and then a 1M ultrasound therapy device was used for 10 minutes, and 1000W / m 2 lighting processing.

[0081] On day -1, MRSA suspension was injected in situ at the wound site. On day 1, obvious bacterial proliferation and wound suppuration were observed at the wound site, indicating that the MRSA-infected diabetic mouse model was successfully constructed (day 0). A digital camera was used to take pictures of the wound site on days 0, 3, 7, and 12 to observe the wound healing under the treatment conditions of different groups. On day 0, there was no significant difference in the wound area of ​​mice in different groups, indicating that the constructed full-thickness skin wound was in a uniform circular state. As the treatment time passed, on day 3, the wounds of each group still had suppuration, but compared with the control group, the wounds of each group had a tendency to shrink. By day 7, the group (P@MZ+Light+US group) to which visible light irradiation and ultrasonic stimulation were applied on the P@MZ fiber dressing showed significant wound healing, showing excellent PTT / PCAT / POD synergistic antibacterial effects, and the removal of bacteria at the wound site greatly promoted wound healing and avoided wound healing stagnation caused by wound infection and inflammation. By the 12th day, the wounds in the P@MZ+Light+US group were almost completely healed, which shows that the built-in electric field formed by P@MZ under ultrasound stimulation effectively promotes the proliferation and migration of damaged tissues, thereby promoting wound healing, which is consistent with the results of in vitro electrical stimulation promoting the proliferation and migration of L929 cells. Figure 6a As shown, Figure 6a Representative skin wound photos on days 0, 3, 7, and 12 after treatment in different groups.

[0082] On the 3rd, 7th and 12th days of treatment, wound tissue was homogenized and coated to evaluate the in vivo antibacterial effect of P@MZ fiber dressing. On the 3rd day of treatment, a large number of colonies were still found on the 3M dressing compared with the control group; interestingly, both PVDF and P@MZ had a certain antibacterial efficiency, which may be because MRSA-infected diabetic wounds are usually moist due to the presence of pus. Therefore, under the action of ultrasound, the charges from the wound electrolytes can interact with oxygen or water molecules to produce ROS, which in turn inactivates the bacteria in the wound. Under light, the antibacterial efficiency in vivo is significantly improved, which is due to the heat generated under light and the heat-promoting photocatalytic effect. In addition, the POD performance at the wound is related to the H secreted by wound bacteria. 2 O 2 The effect produces ·OH, which can also kill bacteria. On the 7th day of treatment, the number of bacterial colonies in the light-exposed group had decreased significantly compared with the 3rd day, indicating that PTT / PCAT / POD has a high in vivo anti-resistant bacteria effect. On the 12th day of treatment, the number of colonies in the control group and the 3M dressing group decreased significantly, which was due to the effect of the mice's own immune system. It is worth noting that the in vivo antibacterial efficiency of the P@MZ+Light+US group on the 12th day was significantly improved, which was based on the significantly improved wound healing rate of mice on the 12th day of treatment; Figure 6b As shown, Figure 6b Photos of plate spreads on days 3, 7 and 12 after treatment with different groups.

[0083] The above 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 principles of the present invention, and these improvements and modifications should also be considered as the protection scope of the present invention. The structures, devices and operating methods not specifically described and explained in the present invention shall be implemented according to the conventional means in the art unless otherwise specified and limited.

Claims

1. Preparation of a piezoelectric enhanced antibacterial composite nano dressing, characterized in that: The following steps are involved: Step 1: Disperse molybdenum metal powder in ethanol solution, stir at room temperature, add H2O2 to obtain a yellow solution, seal it in a stainless steel autoclave, react at 160℃ for 12h, cool to room temperature, wash with ethanol and water three times respectively, and dry it in vacuum at 60℃ overnight to obtain MoO 3-x (M) powder; Step 2: Disperse zinc chloride, ferric chloride hexahydrate, sodium citrate dihydrate, and sodium acetate in ethylene glycol in sequence, dissolve them by ultrasonication to obtain a reddish brown mixed solution, and then transfer the solution to a polytetrafluoroethylene container, react at 200°C for 12 hours, and after cooling to room temperature, wash with ethanol and water for three times respectively, and dry at 60°C for 12 hours to obtain ZnFe2O4(Z) powder; Step 3: Mo metal powder was dispersed in an ethanol solution and stirred at room temperature, and then H2O2 was added to obtain a yellow solution. Z powder was then dispersed in the yellow solution, and after ultrasonic dispersion, it was transferred to a polytetrafluoroethylene container and sealed in a stainless steel autoclave. The reaction was carried out at 160°C for 12 hours. After cooling to room temperature, the mixture was washed with ethanol and water for three times respectively, and dried under vacuum at 60°C overnight to obtain MoO 3-x / ZnFe2O4(MZ) nanocomposite materials; Step 4: Dissolve the MZ nanomaterial in DMF, ultrasonicate for 30 min, then add PVDF powder, and stir magnetically at 42 °C for 12 h to prepare a PVDF spinning solution with uniform MZ dispersion; finally, use the solution jet spinning technology to obtain PVDF@MoO 3-x / ZnFe2O4 (P@MZ) composite nanofiber membrane.

2. The preparation of a piezoelectric enhanced antibacterial composite nano dressing according to claim 1, characterized in that: Nanocomposite MoO 3-x / ZnFe2O4 contains the construction of Z-type heterojunction.

3. The preparation of a piezoelectric enhanced antibacterial composite nano dressing according to claim 1, characterized in that: In the step 4, the specific parameters of the solution jet spinning technology are: needle specification: 23G, propulsion rate: 10mL / h, receiving roller speed: 500rpm, receiving distance: 30cm, wind pressure: 120MPa.

4. Use of the piezoelectric enhanced antibacterial composite nano dressing according to claim 3 in the preparation of a dressing drug for treating external wounds of diabetic patients.

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