A composite piezoelectric negative pressure dressing and a preparation method thereof

Abstract

The present application relates to a kind of composite piezoelectric negative pressure dressings and its preparation method, belong to medical dressing field.The present application includes: step S1: collagen is dissolved in acetic acid to obtain collagen solution, collagen sponge is obtained by freeze-drying process;Step S2: PVDF powder and ZnO nanoparticles are dissolved in organic solvent to obtain PVDF / ZnO solution;Step S3: the injector equipped with PVDF / ZnO solution is placed in electrospinning machine, collagen sponge is fixed on the collection wheel of electrospinning machine, and PVDF / ZnO nanofiber is covered on collagen sponge to form composite piezoelectric dressing by electrospinning method;Step S4: semipermeable membrane is covered on the top layer of composite piezoelectric dressing, while connecting drainage tube, forming negative pressure system, to obtain composite piezoelectric negative pressure dressing.The present application has good biocompatibility.Nanofiber membrane is more sensitive, and controllable negative pressure intensity makes it have excellent stability, and piezoelectric performance is more excellent.

Description

Technical Field

[0001] This invention relates to the field of medical dressings, and more specifically to a composite piezoelectric negative pressure dressing and its preparation method. Background Technology

[0002] The skin is the body's first line of defense, protecting health and preventing the invasion of pathogens. After traumatic injury, exogenous infection, diabetic ulcers, or surgery, the skin's self-healing ability is severely impaired, accompanied by significant bleeding and exudate. Therefore, ideal wound dressings are needed for timely wound management to prevent prolonged exposure of the wound.

[0003] The wound healing process comprises four phases: hemostasis, inflammation, proliferation, and remodeling. The hemostasis phase is the first stage of wound healing, requiring minimizing blood loss and maintaining blood supply to the wound site. The inflammation phase occurs when vascular endothelial growth factor (VEGF) and other growth factors are released at the wound site during the hemostasis phase, recruiting a large number of neutrophils and lymphocytes, triggering an inflammatory response. Neutrophils and lymphocytes can clear pathogens and simultaneously release tumor necrosis factor (TNF) and interleukin-6. The third phase is the proliferation phase, during which a large number of growth factors are released at the wound site, promoting angiogenesis, collagen deposition, elastin synthesis, cell migration and proliferation, and granulation tissue formation. In the final remodeling phase, capillary degeneration, macrophage apoptosis, scar formation, and increased tensile strength at the wound site occur.

[0004] During wound care, wound dressings cover the injured area, maintaining a moist environment and suitable body temperature, providing physical protection and preventing microbial invasion, while also relieving pain. Ideal wound dressings need good biocompatibility and antibacterial properties to avoid excessive inflammation in chronic wounds. Common wound dressings include film dressings, hydrogel dressings, foam dressings, and bio-protein sponges. Collagen is an important component of the extracellular matrix and is crucial for wound closure and tissue integrity. Common chronic wounds such as diabetic foot ulcers easily produce large amounts of exudate. Negative pressure drainage techniques can be used to remove accumulated fluid and necrosis from the tissue, preventing the spread of infection. Controlled negative pressure intensity can maintain blood circulation, promote granulation tissue regeneration, and accelerate wound healing.

[0005] The piezoelectric effect occurs when external mechanical pressure or tension alters the crystal structure of a material in the absence of an external electric field, causing a shift in charge centers within the crystal structure and generating a molecular dipole moment, thus creating a potential difference. PVDF is one of the most common piezoelectric polymers and also possesses good biocompatibility. Its crystal structure significantly influences its piezoelectric properties, with the β phase exhibiting superior piezoelectric performance. The high-voltage electric field during electrospinning can promote the formation of the β phase in the PVDF solution, thereby enhancing its piezoelectric capability. Composite ZnO nanoparticles enhance the piezoelectric response while also exhibiting certain antibacterial effects. Under negative pressure, the composite piezoelectric membrane can generate sustainable piezoelectric voltage and current. The resulting bioelectric stimulation signal can trigger cascade reactions, promoting cell proliferation and migration, orderly collagen deposition, angiogenesis, and upregulating the expression of various growth factors related to wound healing.

[0006] In the prior art, patent application number 202110499780.9, published on May 8, 2021, entitled "A wound dressing based on the piezoelectric effect and its preparation method," discloses a wound dressing based on the piezoelectric effect and its preparation method. This technical solution combines encapsulation material, electrodes, piezoelectric material, substrate, and adhesive together, and sputters electrodes onto the surface of the piezoelectric material to obtain a wound dressing with electrodes. The piezoelectric material generates an electric charge during human movement, which acts on the wound to achieve electrical stimulation, promoting fibroblast proliferation and shortening healing time. However, the method of generating an electric charge through human movement has the potential for unstable electrical stimulation during use, resulting in limited wound healing effects.

[0007] Therefore, designing a negative pressure dressing that can provide a template, has antibacterial properties, and a stable piezoelectric response has promising application prospects and urgently needs further research. Summary of the Invention

[0008] To address the problems existing in the prior art, the purpose of this invention is to provide a collagen sponge template for the regeneration of new tissue. The surface of the collagen sponge is covered with a PVDF / ZnO nanofiber membrane, which enables the composite collagen sponge to generate a piezoelectric effect and also endows the collagen sponge with antibacterial properties. At the same time, the controllable negative pressure value makes the piezoelectric effect more stable. The piezoelectric effect causes a cascade reaction at the wound site, promoting cell proliferation and migration, and orderly collagen deposition, thereby improving the wound healing rate.

[0009] To address the above problems, this invention proposes a composite piezoelectric negative pressure dressing and its preparation method. The specific technical solution of this invention is as follows:

[0010] The present invention provides a composite piezoelectric negative pressure dressing, which is composed of a PVDF / ZnO nanofiber piezoelectric membrane, a collagen sponge layer and a negative pressure drainage layer.

[0011] Another aspect of the present invention provides a method for preparing a composite piezoelectric negative pressure dressing, comprising the following steps:

[0012] S1. Preparation of collagen sponge: Collagen is dissolved in acetic acid solution to obtain collagen solution; it is pre-frozen at -60℃ to -80℃ for 12 to 24 hours, then freeze-dried in a freeze dryer for 40 to 72 hours, and then subjected to vacuum thermal crosslinking treatment to obtain the collagen sponge.

[0013] S2, Preparation method of PVDF / ZnO solution: PVDF powder and ZnO nanoparticles are simultaneously added to a beaker containing one or more organic solvents selected from N,N-dimethylformamide, N,N-dimethylacetamide, acetone, and tetrahydrofuran. After sealing the mixed solution, it is subjected to strong ultrasonic stirring for 30-60 min and then placed in a water bath at 40℃-60℃ and magnetically stirred for 4-12 h to obtain a uniform PVDF / ZnO spinning solution.

[0014] S3. Preparation method of composite piezoelectric dressing: Collagen sponge is fixed on the collecting wheel of an electrospinning machine, and PVDF / ZnO nanofibers are coated onto the collagen sponge by electrospinning to form composite piezoelectric dressing;

[0015] S4. Cover the top layer of the composite piezoelectric dressing with a semi-permeable membrane and connect a drainage tube to form a negative pressure system, thus obtaining a composite piezoelectric negative pressure dressing.

[0016] Furthermore, the porosity of the collagen sponge layer is 60%–90%, and the pore size is 50–200 μm; the porosity of the PVDF / ZnO nanofiber piezoelectric film is 50%–80%, and the pore size is 20–150 μm.

[0017] Furthermore, in step S1, the collagen is derived from one of pig tendon, cow Achilles tendon, or fish skin, the molecular weight of the collagen is 100-550 kDa, the collagen protein mass fraction is 0.5%-10%, and the acetic acid concentration is 0.5%-5% of the collagen solution.

[0018] Furthermore, in step S1, the cross-linking temperature of the collagen sponge is 95–130°C, and the cross-linking time is 24–48 h.

[0019] Furthermore, in step S1, the thickness of the collagen sponge is 1-15 mm.

[0020] Furthermore, in step S2, the mass fraction of PVDF powder is 5% to 30%, the mass fraction of ZnO nanoparticles is 5% to 20% of the mass fraction of PVDF powder, and the particle size is 20 to 150 nm.

[0021] Furthermore, in step S2, the thickness of the PVDF / ZnO nanofiber membrane is 0.5–5 mm.

[0022] Furthermore, in step S3, the needle diameter is 0.15mm to 1mm, the spinning solution ejection speed is 0.5mL / h to 10mL / h, the collector is a rotatable and grounded wheel with a rotation speed of 50r / min to 800r / min, and a voltage of 10kV to 30kV is applied to the spinning head.

[0023] Furthermore, in step S4, the negative pressure value is -80 to -120 mmHg, the negative pressure working time is 2 to 8 minutes, and the working stop time is 1 to 5 minutes.

[0024] The technical effects and advantages of this invention are as follows:

[0025] 1. The present invention provides a composite piezoelectric negative pressure dressing, wherein the collagen sponge layer can stimulate the wound site to recruit fibroblasts and other cells, providing a template for the regeneration of new tissues and providing a buffering effect for the wound site; the collagen sponge has a softer texture and can evenly transmit negative pressure to the wound surface; the composite PVDF nanofiber membrane has good biocompatibility and piezoelectric properties, and the doping with ZnO can improve the piezoelectric properties while also having a certain antibacterial effect, so the composite piezoelectric dressing has good biocompatibility.

[0026] 2. The composite piezoelectric negative pressure dressing prepared by this invention induces a piezoelectric effect in the PVDF / ZnO nanofiber piezoelectric membrane through negative pressure. When the nanofiber membrane is subjected to pressure, it can undergo greater deformation, resulting in a more sensitive response. The controllable negative pressure intensity provides excellent stability and superior piezoelectric performance. Simultaneously, the high-speed rotating collecting wheel facilitates fiber orientation; the high degree of fiber orientation induces β-phase orientation, thereby generating an even higher piezoelectric response. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the preparation process of the composite piezoelectric dressing provided by the present invention;

[0028] Figure 2 This is a schematic diagram of the structure of the composite piezoelectric negative pressure dressing provided by the present invention;

[0029] Figure 3 Piezoelectric curves of composite piezoelectric dressings with different ZnO contents;

[0030] Figure 4 The positive peak voltage of the composite piezoelectric dressing is shown in the figure for different ZnO contents.

[0031] The attached figures are labeled as follows: 1. Semi-permeable membrane; 2. PVDF / ZnO nanofiber piezoelectric membrane; 3. Collagen sponge layer. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0033] It should also be noted that, in order to avoid obscuring the present invention with unnecessary details, only the structures and / or processing steps closely related to the present invention are shown in the accompanying drawings, while other details that are not closely related to the present invention are omitted.

[0034] Additionally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0035] Please see Figures 1 to 2 As shown, the present invention proposes a composite piezoelectric negative pressure dressing and its preparation method, comprising the following steps:

[0036] A composite piezoelectric negative pressure dressing and its preparation method are characterized in that: the composite piezoelectric dressing is composed of a PVDF / ZnO nanofiber piezoelectric membrane, a collagen sponge layer and a negative pressure drainage layer.

[0037] A composite piezoelectric negative pressure dressing and its preparation method are characterized by comprising the following steps:

[0038] S1. Preparation of collagen sponge: Collagen is dissolved in acetic acid solution to obtain collagen solution; it is pre-frozen at -60℃ to -80℃ for 12 to 24 hours, then freeze-dried in a freeze dryer for 40 to 72 hours, and then subjected to vacuum thermal crosslinking treatment to obtain the collagen sponge.

[0039] S2, Preparation method of PVDF / ZnO solution: PVDF powder and ZnO nanoparticles are simultaneously added to a beaker containing one or more organic solvents selected from N,N-dimethylformamide, N,N-dimethylacetamide, acetone, and tetrahydrofuran. After sealing the mixed solution, it is subjected to strong ultrasonic stirring for 30-60 min and then placed in a water bath at 40℃-60℃ and magnetically stirred for 4-12 h to obtain a uniform PVDF / ZnO spinning solution.

[0040] S3. Preparation method of composite piezoelectric dressing: Collagen sponge is fixed on the collecting wheel of an electrospinning machine, and PVDF / ZnO nanofibers are coated onto the collagen sponge by electrospinning to form composite piezoelectric dressing;

[0041] S4. Cover the top layer of the composite piezoelectric dressing with a semi-permeable membrane and connect a drainage tube to form a negative pressure system, thus obtaining a composite piezoelectric negative pressure dressing.

[0042] Preferably, the porosity of the collagen sponge layer is 60%–90%, and the pore size is 50–200 μm; the porosity of the PVDF / ZnO nanofiber piezoelectric membrane is 50%–80%, and the pore size is 20–150 μm.

[0043] Preferably, in step S1, the collagen is derived from one of pig tendon, cow Achilles tendon, or fish skin, the molecular weight of the collagen is 100-550 kDa, the collagen protein mass fraction is 0.5%-10%, and the acetic acid concentration is 0.5%-5% of the collagen solution.

[0044] Preferably, in step S1, the cross-linking temperature of the collagen sponge is 95–130°C, and the cross-linking time is 24–48 h.

[0045] Preferably, the thickness of the collagen sponge in step S1 is 1 to 15 mm. If the thickness of the collagen sponge is too small, the cushioning effect is not obvious; if the thickness of the collagen sponge exceeds 15 mm, the electrospinning effect on its surface is not good.

[0046] Preferably, in step S2, the mass fraction of PVDF powder is 5%–30%, the mass fraction of ZnO nanoparticles is 5%–20% of the mass fraction of PVDF powder, and the particle size is 20–150 nm. If the mass fraction of PVDF is less than 5%, the solution viscosity is too low, and the electric field force on the spinning solution is much greater than the surface tension, resulting in excessively fine fibers. If the mass fraction of PVDF is greater than 30%, the solution viscosity is too high, which can easily clog the needle and is not conducive to fiber formation during electrospinning. If the mass fraction of ZnO nanoparticles is greater than 20%, it is not conducive to the formation of the β phase in PVDF fibers, thereby affecting the piezoelectric response.

[0047] Preferably, in step S2, the thickness of the PVDF / ZnO nanofiber membrane is 0.5–5 mm. If the nanofiber thickness is too small, the piezoelectric response will be weak.

[0048] Preferably, in step S3, the needle diameter is 0.15 mm to 1 mm, the spinning solution ejection speed is 0.5 mL / h to 10 mL / h, the collector is a rotatable and grounded disc with a rotational speed of 50 r / min to 800 r / min, and a voltage of 10 kV to 30 kV is applied to the spinning head. A high collector rotational speed results in good fiber orientation; when the applied voltage is below 10 kV or above 30 kV, fibers cannot be formed.

[0049] Preferably, in step S4, the negative pressure value is -80 to -120 mmHg, the negative pressure working time is 2 to 8 minutes, and the working stop time is 1 to 5 minutes. When the negative pressure value is too low, it is not conducive to local blood circulation; when the negative pressure value is too high, it will cause tissue ischemia; at the same time, the intermittent negative pressure working mode can promote blood circulation and granulation tissue regeneration at the wound site.

[0050] The following specific embodiments further illustrate the composite piezoelectric negative pressure dressing and its preparation method according to the present invention:

[0051] Example 1

[0052] This embodiment describes the preparation of a composite piezoelectric negative pressure dressing and its preparation method, including the following steps:

[0053] S1. Preparation of collagen sponge: Collagen is dissolved in acetic acid solution to obtain collagen solution; it is pre-frozen at -60℃ for 12h, then freeze-dried in a freeze dryer for 40h, and then subjected to vacuum thermal crosslinking treatment to obtain the collagen sponge;

[0054] S2, Preparation method of PVDF / ZnO solution: PVDF powder and ZnO nanoparticles are added to a mixed organic solvent of N,N-dimethylformamide / acetone. After sealing the mixed solution, it is subjected to strong ultrasonic stirring for 30 min and then placed in a water bath at 40℃ and magnetically stirred for 4 h to obtain a uniform PVDF / ZnO spinning solution.

[0055] S3. Preparation method of composite piezoelectric dressing: Collagen sponge is fixed on the collecting wheel of an electrospinning machine, and PVDF / ZnO nanofibers are coated onto the collagen sponge by electrospinning to form composite piezoelectric dressing;

[0056] S4. Cover the top layer of the composite piezoelectric dressing with a semi-permeable membrane and connect a drainage tube to form a negative pressure system, thus obtaining a composite piezoelectric negative pressure dressing.

[0057] The collagen is derived from pig tendon, with a molecular weight of 100 kDa and a protein mass fraction of 5%. Acetic acid concentration is 0.5% of the collagen solution. In step S1, the cross-linking temperature of the collagen sponge is 105℃, and the cross-linking time is 24 hours. The thickness of the collagen sponge in step S1 is 5 mm. In step S2, the mass fraction of PVDF powder is 10%, and the thickness of the PVDF / ZnO nanofiber membrane in step S2 is 1 mm.

[0058] In step S3, the needle diameter is 0.6 mm, the spinning solution ejection speed is 0.5 mL / h, the collector is a rotatable and grounded wheel with a rotation speed of 800 r / min, and a voltage of 15 kV is applied to the spinning head.

[0059] A schematic diagram of the composite piezoelectric dressing structure prepared in this embodiment is shown below. Figure 2 As shown, the composite piezoelectric dressing is placed on a test platform, and an oscilloscope is connected to both poles of the dressing. The positive probe of the oscilloscope is connected to the upper pole of the dressing, and the ground probe is connected to the lower pole. A conduit is positioned directly above the composite piezoelectric dressing, and the conduit is fixed by an iron stand. The oscilloscope records the potential difference between the two poles of the composite piezoelectric dressing during the impact of a small ball, i.e., the open-circuit voltage of the composite piezoelectric dressing. The composite piezoelectric dressing prepared in Example 1 of this application was tested; when the ZnO mass fraction was 0%, the positive peak voltage value of the composite piezoelectric dressing was 3.28V.

[0060] Examples 2 to 5

[0061] The only difference between Examples 2 to 5 and Example 1 is that the mass fraction of ZnO nanoparticles is different in step S2. The other steps are basically the same as in Example 1 and will not be repeated here. The different ZnO mass fraction settings in Examples 1 to 5 are shown in Table 1. The thickness of the piezoelectric nanofiber membranes prepared from PVDF spinning solutions containing 0%, 5%, 10%, 15%, and 20% ZnO mass fractions are all within 1 ± 0.1 mm. The positive peak voltage values ​​of the prepared composite piezoelectric dressings are shown in the table below.

[0062] Table 1. Mass fraction settings of ZnO nanoparticles in Examples 1 to 5 and the peak voltage values ​​of composite piezoelectric dressings prepared under corresponding conditions.

[0063] project Mass fraction of ZnO nanoparticles (%) Positive peak voltage (V) Example 1 0 3.28 Example 2 5 4.24 Example 3 10 8.6 Example 4 15 2.36 Example 5 20 1.44

[0064] In summary, this invention proposes a composite piezoelectric negative pressure dressing and its preparation method. A porous collagen sponge is prepared, and then a PVDF / ZnO nanofiber membrane is coated onto its surface. Using the collagen sponge as a template, the PVDF / ZnO nanofiber membrane is electrospinned to form the composite piezoelectric dressing. A semi-permeable membrane is then attached to the surface of the prepared composite piezoelectric dressing, and a drainage tube is connected to form a negative pressure system. By combining electrospinning with negative pressure drainage, the absorbency of the piezoelectric dressing is improved, reducing exudate from chronic wounds and alleviating inflammatory responses. This effectively solves the problems of unstable piezoelectric effect and poor exudate absorption in existing piezoelectric dressings, which lead to poor healing of chronic wounds. During electrospinning, the high-speed rotating collecting wheel promotes fiber orientation, facilitates the formation of the β phase, and enhances the piezoelectric effect. In the above process, by adjusting parameters such as the thickness of the collagen membrane, the voltage of electrospinning, and the negative pressure value of negative pressure drainage during the preparation process, a composite piezoelectric negative pressure dressing with stable piezoelectric effect, capable of stimulating cell migration and proliferation, promoting collagen deposition, and having antibacterial effects can be obtained.

[0065] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method of preparing a composite piezoelectric negative pressure dressing, characterized by: The composite piezoelectric negative pressure dressing is composed of a PVDF / ZnO nanofiber piezoelectric film, a collagen sponge layer and a negative pressure drainage layer; The preparation method comprises the following steps: S1, preparation of the collagen sponge: collagen is dissolved in an acetic acid solution to obtain a collagen solution; the collagen solution is pre-frozen at-60℃ to-80℃ for 12 to 24 hours, and then placed in a freeze dryer for freeze drying for 40 to 72 hours, and vacuum heat crosslinking treatment is performed to obtain the collagen sponge; S2, preparation method of the PVDF / ZnO solution: PVDF powder and ZnO nanoparticles are simultaneously added to a beaker containing an organic solvent containing one or more of N,N-dimethylformamide, N,N-dimethylacetamide, acetone and tetrahydrofuran, the obtained mixed solution is sealed, and then subjected to 30 to 60 minutes of strong ultrasonic stirring treatment, and then placed in a water bath at 40 to 60°C and subjected to magnetic stirring for 4 to 12 hours to obtain a uniform PVDF / ZnO spinning solution; S3, preparation method of the composite piezoelectric dressing: the collagen sponge is fixed on a collection wheel of an electrospinning machine, and the PVDF / ZnO nanofiber is covered on the collagen sponge by electrospinning to form the composite piezoelectric dressing; S4, covering the semi-permeable membrane on the top layer of the composite piezoelectric dressing; The porosity of the collagen sponge layer is 60% to 90%, and the pore size is 50 to 200μm; the porosity of the PVDF / ZnO nanofiber piezoelectric film is 50% to 80%, and the pore size is 20 to 150μm.

2. The method of claim 1, wherein the piezoelectric composite negative pressure dressing is prepared by the steps of: In step S1, the collagen is derived from one of pig tendon, bovine Achilles tendon and fish skin, the molecular weight of the collagen is 100 to 550kDa, the mass fraction of the collagen is 0.5% to 10%, and the concentration of acetic acid is 0.5% to 5% of the collagen solution.

3. The method of claim 1, wherein the piezoelectric composite negative pressure dressing is prepared by the steps of: In step S1, the crosslinking temperature of the collagen sponge is 95 to 130°C, and the crosslinking time is 24 to 48 hours.

4. The method of claim 1, wherein the piezoelectric composite negative pressure dressing is prepared by the steps of: In step S1, the thickness of the collagen sponge is 1 to 15mm.

5. The method of claim 1, wherein the piezoelectric composite negative pressure dressing is prepared by the steps of: In step S2, the mass fraction of the PVDF powder is 5% to 30%, the mass fraction of the ZnO nanoparticles is 5% to 20% of the mass fraction of the PVDF powder, and the particle size is 20 to 150nm.

6. The method of claim 1, wherein the piezoelectric composite negative pressure dressing is prepared by the steps of: In step S2, the thickness of the PVDF / ZnO nanofiber film is 0.5 to 5mm.

7. The method of claim 1, wherein the piezoelectric composite negative pressure dressing is prepared by the steps of: In step S3, the diameter of the needle is 0.15mm to 1mm, the pushing speed of the spinning solution is 0.5mL / h to 10mL / h, the collector is a rotatable and grounded wheel with a rotation speed of 50r / min to 800r / min, and a voltage of 10kV to 30kV is applied to the spinning head.

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