Body fluid driven biocompatible magnesium metal circular patch battery and preparation and application thereof

Abstract

The invention discloses a biocompatible magnesium metal circular patch battery driven by body fluid and preparation and application of the biocompatible magnesium metal circular patch battery. The battery is formed by taking a disc magnesium alloy as a negative electrode, taking an annular stainless steel mesh as a positive electrode, taking an electrospinning polycaprolactone material as a battery carrier and taking body fluid at a biological wound as electrolyte. The battery shows a stable and continuous discharge effect in simulated body fluid (PBS) and wound in situ. In addition, the battery effectively couples an endogenous electric field existing at a biological wound through an annular electrode combination with positive outside and negative inside, a degradation product generated in the discharging process of the battery serves as a chemical stimulation factor, and the wound healing speed is obviously increased through coupling of the electric field effect and the chemical effect. According to the invention, wound healing is effectively accelerated by providing an effective electrical stimulation synergistic chemical effect; the in-situ annular electrode combined patch battery structure creates a new thought for a degradable biocompatible battery, provides a new stimulation mode, and can be used for promoting wound recovery.

Description

Technical Field

[0001] The present invention belongs to the field of functional biomedical technology, and in particular relates to a biocompatible magnesium metal circular patch battery driven by body fluid, and its preparation and application. Background Art

[0002] Wound management is crucial for the patient's physical recovery. When a wound is formed, due to the directional transmembrane ion transport, an endogenous electric field is generated around the wound and a series of physiological reactions are triggered to gradually close the wound. Applying an exogenous electric field of appropriate intensity to the wound can achieve the effect of promoting wound healing. However, the traditional method of applying DC power stimulation is inconvenient, so the use of lightweight, flexible, and biocompatible implantable self-powered devices to provide long-term and stable electrical stimulation has broad application prospects. Implantable self-powered devices are mainly divided into wireless electrodes, nanogenerators, enzyme fuel cells, and metal fuel cells, but the first three implantable devices have certain limitations, such as wireless implantable electrodes cannot completely get rid of external devices, nanogenerator output is unstable, and enzyme fuel cells have harsh application conditions. In contrast, biocompatible metal fuel cells have the advantages of stable output, high capacity density, and undemanding application conditions.

[0003] The factors that influence the healing effect of implantable self-powered devices include two parts, namely the electric field effect generated between electrodes and the chemical signal effect generated by degradation. Studies have shown that the external electric field is closely related to the recovery of wounds at all stages, and can promote cell proliferation and migration and accelerate the elimination of inflammatory response stages. The electric field strength range for this effect is 10 to 200 mV mm -1 , and the magnesium and molybdenum battery system can output effective electrical stimulation signal potential. In addition, chemical elements also promote wound healing. For a long time, magnesium metal and alloys have been widely used in the research and development of biocompatible devices and battery systems due to their excellent biocompatibility, suitable self-dissolution rate and low electrode potential. In the past, most biocompatible batteries used closed battery systems. Once the electrolyte leaks, it will cause irreversible damage to the organism, which has limited its development to a certain extent. Compared with closed batteries, open batteries driven by body fluids are safer. Therefore, it is worth further exploration to use magnesium metal and other biocompatible metals to form a stable and flexible open battery system. Summary of the invention

[0004] The purpose of the present invention is to provide a biocompatible magnesium metal circular patch battery driven by body fluids and its preparation and application. The open circuit voltage of the circular electrode patch battery is 1.4-1.5V, and the current is 50-400μA / cm 2Under a wide range of discharge current density, the discharge voltage is between 0.4 and 1.3 V, and the discharge time can reach 11 days, which can produce electrical stimulation of sufficient intensity and duration. This patch battery composed of ring electrodes can generate a stable electric field in the same direction as the endogenous electric field at the wound, while coupling the chemical effects produced by battery degradation, effectively promoting wound healing, creating new ideas for biocompatible batteries and providing a new way of electrical stimulation.

[0005] The objective of the present invention is achieved through the following technical solutions:

[0006] <First aspect>

[0007] The present invention provides a biocompatible magnesium metal circular patch battery driven by body fluids. The battery is constructed by using a circular magnesium alloy as a negative electrode, a circular stainless steel mesh as a positive electrode, a polycaprolactone material as a battery carrier, and body fluids from biological wounds as an electrolyte; and the circular magnesium alloy is placed in the inner diameter space of the circular stainless steel mesh.

[0008] As an embodiment, the magnesium alloy disc is concentrically arranged with the annular stainless steel mesh.

[0009] As an embodiment, there is a gap of 1 mm to 2 mm between the positive and negative electrodes.

[0010] As an embodiment, the disk-shaped magnesium alloy and the annular stainless steel mesh are adhered to the polycaprolactone material by biocompatible PVA glue.

[0011] As an embodiment, the hydrophilic PCL electrospinning membrane includes a hydrophilic circular PCL membrane and a hydrophilic annular PCL membrane; the hydrophilic circular PCL membrane is placed on the bottom layer, and the hydrophilic annular PCL membrane is placed on the top layer and partially covers the disc magnesium alloy. That is, the inner diameter of the annular PCL membrane is smaller than the diameter of the disc magnesium alloy. The disc magnesium alloy and the annular stainless steel mesh are adhered to the hydrophilic PCL electrospinning membrane by biocompatible PVA glue.

[0012] <Second Aspect>

[0013] The present invention provides a method for preparing a biocompatible magnesium metal circular patch battery driven by body fluid, the method comprising the following steps:

[0014] S1. Prepare a carrier: place the PCL electrospun membrane in a NaOH solution for hydrolysis to obtain a hydrophilic PCL membrane; cut the membrane into a hydrophilic circular PCL membrane and a hydrophilic annular PCL membrane;

[0015] S2. Assembly: Place a hydrophilic circular PCL membrane on the bottom layer, adhere a disc magnesium alloy negative electrode and a circular stainless steel mesh positive electrode thereon with biocompatible glue, and the disc magnesium alloy is placed in the inner diameter space of the circular stainless steel mesh; then cover and adhere the hydrophilic circular PCL membrane with biocompatible glue; the hydrophilic circular PCL membrane partially covers the disc magnesium alloy negative electrode.

[0016] As an embodiment, the PCL electrospinning membrane is prepared by a method comprising the following steps: dissolving PCL in a mixed organic solvent of hexafluoroisopropanol and N,N-dimethylformamide to prepare a PCL organic solution (i.e., an electrospinning precursor solution), and then preparing a PCL membrane by an electrospinning method.

[0017] As an embodiment, the concentration of PCL in the precursor solution is 12-22 wt %.

[0018] As an embodiment, the volume ratio of hexafluoroisopropanol to N,N-dimethylformamide solvent is 2 to 2.5:1.

[0019] As an embodiment, the concentration of the NaOH solution is 3-5 mol / L.

[0020] As an embodiment, the hydrolysis treatment is carried out at a constant temperature of 40 to 50° C. for 10 to 20 minutes.

[0021] As an embodiment, the biocompatible glue is prepared by dissolving polyvinyl alcohol (PVA) in deionized water and stirring at a constant temperature of 75 to 85° C. until completely dissolved to obtain biocompatible PVA glue; the concentration of the prepared biocompatible PVA glue is 11 to 13 wt %.

[0022] The present invention firstly dissolves PCL in a mixed organic solvent of hexafluoroisopropanol and N,N-dimethylformamide to prepare a PCL organic solution, and then prepares a PCL film by an electrostatic spinning method; subsequently, the PCL film is placed in a NaOH solution for hydrolysis treatment to obtain a hydrophilic PCL film; finally, the magnesium alloy negative electrode and the stainless steel mesh positive electrode sheet are cut into specific shapes and assembled to obtain the novel body fluid-driven and fully degradable magnesium metal circular patch battery of the present invention, which achieves the purpose of promoting wound healing by generating a circular electric field pointing to the center of the wound to couple the endogenous electric field of the wound.

[0023] <Third Aspect>

[0024] The present invention provides a use of the aforementioned magnesium metal circular patch battery, or the magnesium metal circular patch battery prepared by the aforementioned method as a self-powered device for promoting wound healing.

[0025] The magnesium metal circular patch battery of the present invention is used in situ at the wound, and the electric field generated by the annular electrode fully couples the direction of the endogenous electric field of the wound.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1) The novel body fluid-driven biocompatible magnesium metal circular patch battery described in the present invention is composed of a circular positive electrode and a circular metal negative electrode. The electric field generated can effectively match the endogenous electric field of the wound, and at the same time couple the chemical effects produced by the battery degradation products to promote wound healing.

[0028] 2) The in-situ annular electrode patch battery structure of the present invention creates a new idea for biocompatible batteries and provides a new electrical stimulation method that can be used to promote wound recovery. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0030] Figure 1 Schematic diagram of the novel biocompatible magnesium metal circular patch battery driven by body fluids of the present invention; in the figure, 1 is a circular stainless steel mesh electrode, 2 is a hydrophilic circular PCL membrane, 3 is a circular magnesium alloy electrode, and 4 is a hydrophilic circular PCL membrane;

[0031] Figure 2 is the open circuit voltage of the magnesium metal circular patch battery in 1×PBS solution;

[0032] Figure 3 The magnesium metal round patch battery has a current range of 0 to 400 μA cm -2 Discharge voltage and discharge duration in 1×PBS solution at discharge current density;

[0033] Figure 4 This is the fitted electric field intensity distribution diagram of the magnesium metal circular patch battery;

[0034] Figure 5 The photos are of wound healing of the control group (rats without the battery implanted) and the battery implanted rats;

[0035] Figure 6 The figure is a comparison of the wound healing rates of the control group (rats without the battery implanted) and the battery implanted group. DETAILED DESCRIPTION

[0036] The present invention is described in detail below in conjunction with embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, some adjustments and improvements can also be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0037] Example

[0038] This embodiment provides a biocompatible magnesium metal circular patch battery based on body fluid drive, such as Figure 1 As shown, the round magnesium alloy electrode 3 and the annular stainless steel mesh electrode 1 are placed on the hydrophilic circular PCL film 2, and another hydrophilic annular PCL film 4 is taken to cover the electrode sheet, thereby obtaining the novel body fluid-driven biocompatible magnesium metal round patch battery described in the present invention.

[0039] Among them, the hydrophilic circular PCL membrane as the base layer is a PCL electrospun membrane with no hole in the center, and the thickness is 0.2mm; the hydrophilic annular PCL membrane as the top layer is a PCL electrospun membrane with a hole in the center, and the thickness is 0.3mm.

[0040] The base layer and the top layer are prepared by the following steps:

[0041] 1) Dissolve 1.5 g PCL in a mixed organic solvent of 7 ml hexafluoroisopropanol and 3 ml N,N-dimethylformamide, stir under magnetic heating, and obtain an electrospinning precursor solution after all PCL is dissolved. Use an electrospinning method to spin the PCL solution to obtain a PCL film.

[0042] 2) The PCL electrospun membrane was cut into a circular PCL membrane with a diameter of 16 mm and a ring-shaped PCL membrane with an outer diameter of 16 mm and an inner diameter of 4 mm, and was placed in a 5 mol / L NaOH solution for hydrolysis and kept at 50°C for 10 min to obtain a modified hydrophilic circular PCL membrane and a hydrophilic ring-shaped PCL membrane.

[0043] The disc magnesium alloy electrode is AZ31 magnesium alloy, has a thickness of 0.3 mm, and is in the shape of a disc with a diameter of 6 mm.

[0044] The annular stainless steel mesh electrode is a 316L stainless steel mesh, 200 mesh, in the shape of an annular ring with an outer diameter of 12 mm and an inner diameter of 8 mm.

[0045] The preparation process of the patch battery of this embodiment is as follows:

[0046] A layer of PVA adhesive was applied on the circular hydrophilic PCL electrospun membrane of the substrate layer, and then the circular 316L stainless steel mesh positive electrode and the AZ31 magnesium disc negative electrode were pressed Figure 1The relative positions shown are concentrically adhered to the substrate layer. Next, a layer of PVA glue is applied again on the positive and negative electrode surfaces, and the top layer of annular hydrophilic PCL electrospinning membrane is covered on the positive electrode and partially covered on the negative electrode surface, thus obtaining the biocompatible magnesium metal circular patch battery driven by body fluids. The PVA adhesive is prepared by the following steps: dissolving PVA in deionized water, stirring magnetically at 80°C, and obtaining biocompatible PVA glue after complete dissolution.

[0047] For the application of the battery, this example implanted it subcutaneously in the wound of a rat, with the annular PCL layer attached to the wound. Since the PCL membrane is water permeable and hydrophilic, body fluids enter the battery through the PCL membrane, driving the battery to discharge, and the battery was removed after 5 days of action. The battery discharge reaction is as follows:

[0048] Negative electrode: Mg→Mg 2+ +2e - ,

[0049] Positive electrode: O2+2H2O+4e - →4OH - ,

[0050] or 2H2O+2e - →H2+2OH - .

[0051] The voltage of the circular electrode patch battery under open circuit conditions in PBS simulated body fluid is 1.4~1.5V ( Figure 2 ). In the range of 50 to 400 μA cm -2 Under a wide range of discharge current density, the discharge voltage is between 0.4 and 1.3 V, and the discharge duration can reach 11 days, which can produce electrical stimulation of sufficient intensity and duration ( Figure 3 ). COMSOL software was used to fit the electric field around the patch battery, which showed that the battery could generate a circular electric field pointing to the wound center to couple the endogenous electric field of the wound. The electric field strength was 10-133 mV mm -1 ( Figure 4 ).

[0052] The battery was implanted subcutaneously in the wound of rats with a diameter of 10 mm. The battery was removed after 5 days of action. It can be seen that the wound healing rate of the battery-implanted group was significantly higher than that of the control group, verifying that the biocompatible magnesium metal circular patch battery based on body fluid drive can effectively promote wound healing ( Figure 5 , 6).

[0053] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A biocompatible magnesium metal circular patch battery driven by body fluids, characterized in that: The battery is constructed by using a disk magnesium alloy as a negative electrode, a ring-shaped stainless steel mesh as a positive electrode, a polycaprolactone material as a battery carrier, and body fluid from a biological wound as an electrolyte; and the disk magnesium alloy is placed in the inner diameter space of the ring-shaped stainless steel mesh.

2. The magnesium metal round patch battery according to claim 1, characterized in that: The battery has the following technical features: A , the magnesium alloy disc and the annular stainless steel mesh are arranged concentrically; B. There is a gap of 1mm to 2mm between the positive and negative electrodes; C. The magnesium alloy disc and the annular stainless steel mesh are adhered to the polycaprolactone material by biocompatible PVA glue.

3. The magnesium metal round patch battery according to claim 1, characterized in that: The polycaprolactone material is a hydrophilic PCL electrospinning membrane.

4. The magnesium metal round patch battery according to claim 3, characterized in that: The hydrophilic PCL electrospinning membrane comprises a hydrophilic circular PCL membrane and a hydrophilic annular PCL membrane; the hydrophilic circular PCL membrane is placed on the bottom layer, and the hydrophilic annular PCL membrane is placed on the top layer and partially covers the magnesium alloy disc.

5. A method for preparing a magnesium metal circular patch battery according to any one of claims 1 to 4, characterized in that: The method comprises the following steps: S1. Prepare a carrier: place the PCL electrospun membrane in a NaOH solution for hydrolysis to obtain a hydrophilic PCL membrane; cut the membrane into a hydrophilic circular PCL membrane and a hydrophilic annular PCL membrane; S2. Assembly: Place a hydrophilic circular PCL membrane on the bottom layer, adhere a disc magnesium alloy negative electrode and a circular stainless steel mesh positive electrode thereon with biocompatible glue, and the disc magnesium alloy is placed in the inner diameter space of the circular stainless steel mesh; then cover and adhere the hydrophilic circular PCL membrane with biocompatible glue; the hydrophilic circular PCL membrane partially covers the disc magnesium alloy negative electrode.

6. The preparation method according to claim 5, characterized in that: The method comprises at least one of the following technical features: D. During assembly, the hydrophilic circular PCL membrane, the disc-shaped magnesium alloy negative electrode, the annular stainless steel mesh positive electrode and the hydrophilic annular PCL membrane are assembled concentrically; E. The PCL electrospinning membrane is prepared by a method comprising the following steps: dissolving a certain amount of PCL in a mixed organic solvent of hexafluoroisopropanol and N,N-dimethylformamide to obtain an electrospinning precursor solution; preparing a PCL electrospinning membrane by an electrospinning method; the concentration of PCL in the precursor solution is 12 to 22 wt%, and the volume ratio of hexafluoroisopropanol to N,N-dimethylformamide solvent is 2 to 2.5:

1.

7. The preparation method according to claim 5, characterized in that: The concentration of the NaOH solution is 3-5 mol / L, and the hydrolysis treatment is carried out at a constant temperature of 40-50° C. for 10-20 minutes.

8. The preparation method according to claim 5, characterized in that: The biocompatible glue is prepared by dissolving polyvinyl alcohol in deionized water, stirring at a constant temperature of 75-85° C. until the water is completely dissolved, to obtain biocompatible PVA glue; the concentration of the prepared biocompatible PVA glue is 11-13 wt %.

9. Use of the magnesium metal circular patch battery as claimed in any one of claims 1 to 4, or the magnesium metal circular patch battery prepared by the method as claimed in claims 5 to 8 as a self-powered device for promoting wound healing.

10. The use according to claim 9, characterized in that The magnesium metal circular patch battery is used in situ at the wound, and the electric field generated by the annular electrode fully couples the direction of the endogenous electric field of the wound.

Images