Degradable flexible devices for regulating the degradation of medical magnesium alloys

Abstract

The present invention discloses a degradable flexible device for regulating the degradation of a medical magnesium alloy. The device comprises a magnesium electrode (10), a first molybdenum wire conductor (11), a hydrogel electrolyte (20), a molybdenum oxide electrode (30), a second molybdenum wire conductor (31), and a PLGA flexible film (40). The molybdenum wire length reserved on the second molybdenum wire conductor (31) is referred to as the molybdenum oxide wire coil (50). The resistance of the molybdenum oxide wire coil (50) is 1000 to 8000 ohms, and the coil length is 10 to 30 centimeters. When the magnesium electrode (10) is connected to the medical magnesium alloy, the medical magnesium alloy implanted in the body can be slowly degraded, and the corrosion rate is reduced by 15.7% to 20.0%. When the molybdenum oxide electrode (30) is connected to the medical magnesium alloy, the medical magnesium alloy implanted in the body can be quickly degraded, and the corrosion rate is increased by 76.3% to 85.0%.

Description

Technical Field

[0001] The present invention relates to an implantable biodegradable flexible device, and more particularly to a biodegradable flexible device capable of regulating the degradation rate of medical magnesium alloy and medical magnesium alloy devices. Background Art

[0002] In April 2013, Volume 10, Issue 2 of the journal "Orthopedic Biomaterials and Clinical Research" published an article titled "Research Progress of Biodegradable Magnesium Alloys in Cardiovascular and Orthopedic Applications," by authors Jing Yongbin, Zhuang Jinpeng, and Yan Jinglong. The article describes the use of magnesium alloys as stent structures implanted in the human body to provide support, and their ability to self-degrade after the support is removed.

[0003] Katharina et al. published a magnesium alloy (Mg2Ag) bone nail in Acta Biomaterialia. This nail, implanted in the femur of a mouse, exhibited an in vitro corrosion rate of 0.473±0.038 mm / year. In vivo, the Mg2Ag nail degraded within 210 days under non-fracture conditions and 133 days under fracture conditions.

[0004] Magnesium and magnesium alloys are currently the most widely studied and applied biodegradable metal materials. Compared with traditional medical metal materials and degradable polymer materials, they have the advantages of excellent mechanical properties, biodegradability, and good biocompatibility. When magnesium and magnesium alloy devices are implanted in the human body, they need to be stable for a long enough time to allow the human tissue to have sufficient healing time. However, on the one hand, the standard electrode potential of magnesium is low (-2.37V), and its chemical properties are very active. It is very easy to corrode in the physiological environment of the human body. The non-dense oxide film generated on the surface during the corrosion process of magnesium cannot provide good protection for the substrate; on the other hand, magnesium and magnesium alloy devices will release a certain amount of Mg during the degradation process. 2+ , H2 and OH － , excess H2 and OH － In a short period of time, it will form aggregates and bubbles in the subcutaneous tissue, causing inflammation and loosening of the implant, resulting in early implant failure. In addition, a large amount of OH － It will change the pH value of the environment around the tissue and cause alkali poisoning; furthermore, excessive corrosion will cause the mechanical properties of magnesium and magnesium alloy devices to decline rapidly.

[0005] Therefore, developing a device to regulate the degradation rate of medical magnesium alloys is extremely important. Researchers have attempted to control the degradation rate of magnesium alloy orthopedic stents by using nanogenerators to energize them. However, nanogenerators have drawbacks such as limited current flow and the non-degradable material, requiring secondary surgery for removal. Therefore, the degradable flexible device designed in this invention is expected to provide a suitable degradation solution for magnesium alloy stents. Summary of the Invention

[0006] To control the degradation rate of medical magnesium alloys, the present invention has designed a biodegradable flexible device for this purpose. This device exhibits excellent biocompatibility and is fully degradable after implantation in the human body, addressing the technical challenge of rapid and uncontrollable degradation of medical magnesium alloys and medical magnesium alloy devices implanted in the human body. The technical approach utilizes the electrical current generated by the biodegradable flexible device to achieve controlled degradation of the medical magnesium alloy.

[0007] Traditional medical magnesium alloy devices degrade rapidly after implantation, leading to a rapid decline in their mechanical properties and the release of hydrogen that can cause adverse reactions such as inflammation. The degradable flexible device provided by the present invention is connected to the medical magnesium alloy device. By applying an external current to the medical magnesium alloy device, the device is controlled and degraded. Once the device has completed its function, it can be removed without a secondary surgical procedure, alleviating the patient's pain.

[0008] The present invention provides a degradable flexible device for regulating the degradation of a medical magnesium alloy, comprising a magnesium electrode (10), a first molybdenum wire conductor (11), a hydrogel electrolyte (20), a molybdenum oxide electrode (30), a second molybdenum wire conductor (31), and a PLGA flexible film (40); the molybdenum wire length reserved on the second molybdenum wire conductor (31) is referred to as the molybdenum oxide wire coil (50); the hydrogel electrolyte (20) is first placed between the magnesium electrode (10) and the molybdenum oxide electrode (30) to form a laminated structure; and the laminated structure and the molybdenum wire coil (50) are then wrapped with the PLGA flexible film (40), leaving the other end of the first molybdenum wire conductor (11) and the other end of the second molybdenum wire conductor (31) exposed;

[0009] One end of the first molybdenum wire (11) is connected to the magnesium electrode (10); the other end of the first molybdenum wire (11) is connected to a magnesium alloy device implanted in a human body; or, one end of the second molybdenum wire (31) is connected to the molybdenum oxide electrode (30); the other end of the second molybdenum wire (31) is connected to the magnesium alloy device implanted in a human body.

[0010] The present invention provides a method for preparing a degradable flexible device for regulating the degradation of medical magnesium alloys, characterized by comprising the following steps:

[0011] Step 1, preparing a PLGA flexible film (40);

[0012] Step 11, adding PLGA powder to an organic solvent, ultrasonically mixing, and then magnetically stirring to obtain a uniform PLGA dispersion solution;

[0013] Wherein, the mass concentration of PLGA in the PLGA dispersion solution is 10 to 100 g / L;

[0014] The organic solvent is chloroform, tetrahydrofuran or ethyl acetate;

[0015] Step 12, spin coating the PLGA dispersion solution on the substrate at a spin coating speed of 500-1000 r / min, and then treating in a drying oven at 60-100° C. for 18-24 hours to obtain a PLGA flexible film (40);

[0016] The thickness of the prepared PLGA flexible film (40) is 200 microns to 500 microns;

[0017] The prepared PLGA flexible film (40) will be used as the encapsulation layer of the degradable flexible device;

[0018] Step 2: preparing the electrodes required for the degradable flexible device;

[0019] Step 21, preparing a molybdenum oxide electrode (30) by anodizing;

[0020] The molybdenum foil is ultrasonically treated with a dilute hydrochloric acid solution for 3 to 10 minutes to remove the oxide layer formed on the surface of the molybdenum foil, and then cleaned with acetone, anhydrous ethanol, and deionized water in sequence; then, the clean molybdenum foil is anodized to form molybdenum oxide on the surface, thereby preparing a molybdenum oxide electrode (30), the molybdenum oxide electrode (30) having a thickness of 0.1 to 0.5 mm;

[0021] The percentage concentration of dilute hydrochloric acid solution is 5 to 15;

[0022] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20-40KHz, treatment power is 500-2500W, and treatment temperature is 10℃-30℃;

[0023] Anodic oxidation treatment process conditions: Molybdenum foil is set up in a three-electrode system, with the working electrode being molybdenum foil, the counter electrode being a platinum electrode, and the reference electrode being a saturated calomel electrode. A voltage of 0.8V to 1.5V is applied for 4min to 10min.

[0024] Step 22, preparing a magnesium electrode 10;

[0025] The magnesium foil is cleaned with acetone, anhydrous ethanol and deionized water in sequence to remove surface dirt to obtain a clean magnesium electrode (10), wherein the thickness of the magnesium electrode (10) is 0.1 to 0.5 mm;

[0026] Step 3, preparing the electrolyte 20 of the degradable flexible device;

[0027] Step 31, add 0.8-1.0 g of dipotassium hydrogen phosphate and 3.0-3.5 g of sodium dihydrogen phosphate to 1 L of deionized water, stir evenly, then add 30.0-50.0 g of sodium alginate powder, stir evenly to obtain an electrolyte solution;

[0028] Step 32, adding calcium chloride solution to the electrolyte solution for calcium ion cross-linking to obtain a sodium alginate hydrogel electrolyte (20);

[0029] The mass concentration of calcium chloride in the calcium chloride solution is 300-500 g / L;

[0030] Step 4, preparing a molybdenum oxide wire coil (50);

[0031] The molybdenum wire is ultrasonically treated with a dilute hydrochloric acid solution for 3 to 10 minutes to remove the oxide layer formed on the surface of the molybdenum wire, and then cleaned with acetone, anhydrous ethanol, and deionized water in sequence; then, the clean molybdenum wire is anodized to form molybdenum oxide on the surface, and is wound into a ring to obtain an oxide molybdenum wire coil (50);

[0032] The percentage concentration of dilute hydrochloric acid solution is 5 to 15;

[0033] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20-40KHz, treatment power is 500-2500W, and treatment temperature is 10-60℃;

[0034] Anodic oxidation treatment process conditions: The molybdenum wire is set up in a three-electrode system, with the working electrode being molybdenum foil, the counter electrode being a platinum electrode, and the reference electrode being a saturated calomel electrode. A voltage of 0.8V to 1.5V is applied for 4min to 10min.

[0035] Step 5: stacking the layers to produce a degradable flexible device;

[0036] Step 51, stacking and laying electrodes;

[0037] A magnesium electrode (10), a hydrogel electrolyte (20), and a molybdenum oxide electrode (30) are stacked in this order to obtain a sandwich structure, wherein the three electrodes should completely overlap after being stacked;

[0038] Step 52, setting the wire;

[0039] One end of a first molybdenum wire (11) is connected to the magnesium electrode (10), and the other end of the first molybdenum wire (11) is exposed;

[0040] One end of a second molybdenum wire (31) is connected to the molybdenum oxide electrode (30), and the other end of the second molybdenum wire (31) is exposed;

[0041] Step 53, packaging;

[0042] The laminated structure and the molybdenum wire coil (50) are wrapped and packaged with a PLGA flexible film (40), and the other end of the first molybdenum wire conductor (11) and the other end of the second molybdenum wire conductor (31) are exposed, thereby obtaining a degradable flexible device. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 It is a cross-sectional structural diagram of the degradable flexible device for regulating the degradation of medical magnesium alloy according to the present invention.

[0044] Figure 2A This is a photo of the transparent film of the sodium alginate hydrogel electrolyte prepared in step three of the present invention.

[0045] Figure 2B This is a scanning electron microscope image of the sodium alginate hydrogel electrolyte prepared in step three of the present invention.

[0046] Figure 3 The following are comparative photos of the in vitro degradation of the degradable flexible device prepared in Example 1 of the present invention placed in a PBS solution at different times.

[0047] Figure 4 The degradable flexible device prepared in Example 1 of the present invention and sample B were placed in a PBS solution, and the amount of hydrogen released at different times was compared.

[0048] Figure 5A This is a photo of the biocompatibility of the hydrogel electrolyte in a 100% concentration extract.

[0049] Figure 5B This is a photo of the biocompatibility of the hydrogel electrolyte in a 50% concentration extract.

[0050] Figure 5C This is a photo of the biocompatibility of the hydrogel electrolyte in a 25% concentration extract.

[0051] Figure 5D The hydrogel electrolyte was tested for its non-toxicity in NiH3T3 cells.

[0052] Figure 6 The degradable flexible device prepared in Example 2 of the present invention and sample B were placed in a PBS solution, and the hydrogen release amounts at different times were compared.

[0053] Figure 7The degradable flexible device prepared in Example 3 of the present invention and sample B were placed in a PBS solution, and the hydrogen release amounts at different times were compared.

[0054] Figure 8 The degradable flexible device prepared in Example 4 of the present invention and sample B were placed in a PBS solution, and the hydrogen release amounts at different times were compared. DETAILED DESCRIPTION

[0055] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0056] (1) The preparation of the degradable flexible device of the present invention includes the following steps:

[0057] Step 1, preparing a PLGA flexible film 40;

[0058] Step 11: adding PLGA powder to an organic solvent, ultrasonically mixing, and then magnetically stirring to obtain a uniform PLGA dispersion solution.

[0059] The mass concentration of PLGA in the PLGA dispersion solution is 10-100 g / L.

[0060] The organic solvent is chloroform, tetrahydrofuran or ethyl acetate.

[0061] Step 12: Spin-coat the PLGA dispersion solution on the substrate at a spin-coating speed of 500-1000 r / min, and then treat in a drying oven at 60-100° C. for 18-24 hours to obtain a PLGA flexible film 40 .

[0062] The thickness of the prepared PLGA flexible film 40 is 200 micrometers to 500 micrometers.

[0063] The prepared PLGA flexible film 40 will serve as the encapsulation layer of the degradable flexible device.

[0064] In the present invention, the PLGA powder used is brand 900664, manufactured by SIGMA Corporation of the United States, and comprises 50% lactic acid and 50% glycolic acid. For example, a PLGA powder represented by 75:25 comprises 75% lactic acid and 25% glycolic acid. Different monomer ratios can be used to prepare different types of PLGA powders.

[0065] Step 2: preparing the electrodes required for the degradable flexible device;

[0066] Step 21, preparing a molybdenum oxide electrode 30 by anodization;

[0067] The molybdenum foil was ultrasonically treated with a dilute hydrochloric acid solution for 3 to 10 minutes to remove the oxide layer formed on the surface of the molybdenum foil. The foil was then cleaned sequentially with acetone, anhydrous ethanol, and deionized water. Subsequently, the clean molybdenum foil was anodized to form molybdenum oxide on the surface, thereby preparing a molybdenum oxide electrode 30. The thickness of the molybdenum oxide electrode 30 was 0.1 to 0.5 mm.

[0068] The percentage concentration of the dilute hydrochloric acid solution is 5 to 15.

[0069] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20-40KHz, treatment power is 500-2500W, and treatment temperature is 10℃-30℃.

[0070] Anodic oxidation treatment process conditions: The molybdenum foil is set up in a three-electrode system, with the working electrode being the molybdenum foil, the counter electrode being the platinum electrode, and the reference electrode being the saturated calomel electrode. A voltage of 0.8V to 1.5V is applied for a time of 4min to 10min.

[0071] In the present invention, the three-electrode system adopts the German Zahner elektrik IM6e electrochemical workstation.

[0072] Step 22, preparing a magnesium electrode 10;

[0073] The magnesium foil is cleaned with acetone, anhydrous ethanol and deionized water in sequence to remove surface contaminants to obtain a clean magnesium electrode 10 . The thickness of the magnesium electrode 10 is 0.1 to 0.5 mm.

[0074] Step 3, preparing the electrolyte 20 of the degradable flexible device;

[0075] In step 31, 0.8-1.0 g of dipotassium hydrogen phosphate and 3.0-3.5 g of sodium dihydrogen phosphate are added to 1 L of deionized water, and the mixture is stirred evenly. Then, 30.0-50.0 g of sodium alginate powder is added and the mixture is stirred evenly to obtain an electrolyte solution.

[0076] Step 32: Adding calcium chloride solution to the electrolyte solution for calcium ion cross-linking to obtain the sodium alginate hydrogel electrolyte 20.

[0077] In the present invention, the mass concentration of calcium chloride in the calcium chloride solution is 300-500 g / L.

[0078] Step 4: preparing a molybdenum oxide wire coil 50;

[0079] The molybdenum wire is ultrasonically treated with a dilute hydrochloric acid solution for 3 to 10 minutes to remove the oxide layer formed on the surface of the molybdenum wire. The wire is then cleaned with acetone, anhydrous ethanol, and deionized water. Subsequently, the clean molybdenum wire is anodized to form molybdenum oxide on the surface. The molybdenum oxide wire coil 50 is then wound into a ring.

[0080] The percentage concentration of the dilute hydrochloric acid solution is 5 to 15.

[0081] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20-40KHz, treatment power is 500-2500W, and treatment temperature is 10-60°C.

[0082] Anodic oxidation treatment process conditions: The molybdenum wire is set up in a three-electrode system, the working electrode is molybdenum foil, the counter electrode is a platinum electrode, and the reference electrode is a saturated calomel electrode. A voltage of 0.8V to 1.5V is applied for 4min to 10min.

[0083] In the present invention, the molybdenum wire is a 0.1-0.5 mm diameter molybdenum wire produced by Hunan Rare Earth Metal Materials Research Institute Co., Ltd. The resistance of the anodized molybdenum wire coil 50 is 1000-8000 ohms, and the coil length is 10-30 cm.

[0084] Step 5: stacking the layers to produce a degradable flexible device;

[0085] Step 51, stacking and laying electrodes;

[0086] The magnesium electrode 10, the hydrogel electrolyte 20, and the molybdenum oxide electrode 30 are stacked in this order to obtain a sandwich structure, wherein the three should completely overlap after being stacked.

[0087] Step 52, setting the wire;

[0088] One end of a first molybdenum wire 11 is connected to the magnesium electrode 10, and the other end of the first molybdenum wire 11 is exposed;

[0089] One end of a second molybdenum wire 31 is connected to the molybdenum oxide electrode 30 , and the other end of the second molybdenum wire 31 is exposed;

[0090] Step 53, packaging;

[0091] The laminated structure and the molybdenum wire coil 50 are wrapped and packaged with a PLGA flexible film 40, and the other end of the first molybdenum wire conductor 11 and the other end of the second molybdenum wire conductor 31 are exposed, thereby obtaining a degradable flexible device.

[0092] (2) Structure of degradable flexible devices

[0093] See also Figure 1 As shown, the present invention designs a degradable flexible device for regulating the degradation of medical magnesium alloy, which consists of a magnesium electrode 10, a first molybdenum wire 11, a hydrogel electrolyte 20, a molybdenum oxide electrode 30, a second molybdenum wire 31 and a PLGA flexible film 40.

[0094] The remaining length of molybdenum wire on the second molybdenum wire conductor 31 is called the molybdenum oxide wire coil 50. The length of the molybdenum oxide wire coil 50 is designed to regulate the output current of the degradable flexible device. The resistance of the molybdenum oxide wire coil 50 is 1000 to 8000 ohms, and the coil length is 10 to 30 centimeters.

[0095] First, the hydrogel electrolyte 20 is placed between the magnesium electrode 10 and the molybdenum oxide electrode 30 to form a laminated structure; then the laminated structure and the molybdenum wire coil 50 are wrapped with a PLGA flexible film 40, and the other end of the first molybdenum wire conductor 11 and the other end of the second molybdenum wire conductor 31 are exposed.

[0096] One end of the first molybdenum wire conductor 11 is connected to the magnesium electrode 10; the other end of the first molybdenum wire conductor 11 is connected to the magnesium alloy device implanted in the human body; or: one end of the second molybdenum wire conductor 31 is connected to the molybdenum oxide electrode 30; the other end of the second molybdenum wire conductor 31 is connected to the magnesium alloy device implanted in the human body.

[0097] In the present invention, the molybdenum oxide electrode 30 serves as the working electrode of the degradable flexible device.

[0098] The degradable flexible device designed in the present invention has a molybdenum oxide wire of a certain length reserved on the second molybdenum wire conductor 31 as a molybdenum wire coil 50 in order to achieve the regulation of the output current of the molybdenum oxide electrode 30. The length is measured by the resistance value of the molybdenum oxide wire coil 50 to meet the output current regulation of the molybdenum oxide electrode 30.

[0099] (III) Hydrogen release test of degradable flexible devices

[0100] In the present invention, the medical magnesium alloy device equipped with the degradable flexible device of the present invention is referred to as sample A during the degradation analysis. The medical magnesium alloy device not equipped with the degradable flexible device of the present invention is referred to as sample B during the degradation analysis.

[0101] In the present invention, the medical magnesium alloy device is connected to the magnesium electrode 10 in the degradable flexible device through the other end of the first molybdenum wire conductor 11, which can reduce the corrosion rate of the medical magnesium alloy device (i.e., slow degradation). Comparison of degradation effects: Sample A and sample B are placed in a phosphate-balanced saline (PBS) solution, in a sealed environment at a constant temperature of 37.5°C, and immersed for 72 hours to 240 hours, and the amount of hydrogen released is recorded every 12 hours. The corrosion rates of sample A and sample B can be characterized based on the hydrogen release rate. At the same time, the hydrogen release of sample A is 15.7% to 20.0% lower than that of sample B. The hydrogen release rate is significantly reduced, indicating that the corrosion rate of sample A is suppressed.

[0102] In the present invention, the medical magnesium alloy device is connected to the anodized molybdenum electrode 30 in the degradable flexible device through the other end of the second molybdenum wire 31, which can increase the corrosion rate of the medical magnesium alloy device (i.e., rapid degradation). Comparison of degradation effects: Sample A and sample B are placed in a phosphate-balanced saline (PBS) solution, in a sealed environment at a constant temperature of 37.5°C, and immersed for 72 hours to 240 hours, and the amount of hydrogen released is recorded every 12 hours. The corrosion rates of sample A and sample B can be characterized based on the hydrogen release rate. At the same time, the hydrogen release of sample A is 76.3% to 85.0% higher than that of sample B. The hydrogen release rate is significantly improved, indicating that the corrosion rate of sample A is significantly improved.

[0103] Example 1 Slow degradation

[0104] Step 1, preparing a PLGA flexible film;

[0105] PLGA powder is a polylactic acid-glycolic acid copolymer with a ratio of 50% lactic acid and 50% glycolic acid.

[0106] Step 11: adding PLGA powder to chloroform, ultrasonically mixing, and then magnetically stirring to obtain a uniform PLGA dispersion solution; wherein the mass concentration of PLGA powder in the PLGA dispersion solution is 10 g / L.

[0107] Step 12: Spin-coat the PLGA dispersion solution on the glass substrate at a spin-coating speed of 600 r / min, and then treat it in a drying oven at 80° C. for 24 hours to obtain a PLGA flexible film with a thickness of 200 μm.

[0108] Step 2: preparing the electrodes required for the degradable flexible device;

[0109] Step 21, preparing a molybdenum oxide electrode by anodization;

[0110] Molybdenum foil was ultrasonically treated in a 10wt% dilute hydrochloric acid solution for 10 minutes to remove the oxide layer on the surface. The foil was then cleaned with acetone, anhydrous ethanol, and deionized water, sequentially. Subsequently, the cleaned foil was anodized in an electrochemical workstation (Zahner Elektrik IM6e, Germany) at 0.8V for 5 minutes to form molybdenum oxide on the surface, thus preparing a molybdenum oxide electrode. The molybdenum foil dimensions were 10×10×0.2mm.

[0111] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20KHz, treatment power is 1000W, and treatment temperature is 30℃.

[0112] Step 22, preparing a magnesium electrode;

[0113] Acetone, anhydrous ethanol, and deionized water were used to clean the magnesium foil in sequence. The cleaned magnesium foil was used as the magnesium electrode. The size of the magnesium foil was 10×10×0.4 mm.

[0114] Step 3, preparing an electrolyte for a degradable flexible device;

[0115] In step 31, 0.85 g of dipotassium hydrogen phosphate and 3.35 g of sodium dihydrogen phosphate were added to 1 L of deionized water, and the mixture was stirred evenly. Then, 40.0 g of sodium alginate powder was added and the mixture was stirred evenly to obtain an electrolyte solution.

[0116] Step 32: Add a calcium chloride solution with a concentration of 400 g / L into the electrolyte solution for calcium ion cross-linking to obtain a sodium alginate hydrogel electrolyte with a thickness of 1 mm.

[0117] The photo of the sodium alginate hydrogel electrolyte prepared in step 3 is as follows Figure 2A As shown in Figure 2, sodium alginate forms a transparent film with good flexibility under the cross-linking of mixed electrolytes, which can maintain its original performance under mechanical deformation conditions. Figure 2B As shown in the figure, the cross-linked hydrogel is a highly porous three-dimensional structure. This porous structure can store a large amount of electrolyte solution, ensuring the ionic conductivity of the hydrogel.

[0118] Step 4, preparing a molybdenum oxide wire coil;

[0119] Molybdenum wire was ultrasonically treated in a 10wt% dilute hydrochloric acid solution for 10 minutes to remove the oxide layer on the wire surface. The wire was then cleaned with acetone, anhydrous ethanol, and deionized water, sequentially. Subsequently, the cleaned wire was anodic-oxidized in an electrochemical workstation (Zahner Elektrik IM6e, Germany) at 0.8V for 5 minutes, forming molybdenum oxide on the surface. This was then wound into a ring to produce a molybdenum oxide wire coil.

[0120] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20KHz, treatment power is 1000W, and treatment temperature is 30℃.

[0121] The molybdenum wire used was 0.2mm in diameter and produced by Hunan Rare Earth Metal Materials Research Institute Co., Ltd. The anodized molybdenum wire coil had a resistance of 1500 ohms and a coil length of 20 cm. Six turns were made around a diameter of 1 mm.

[0122] Step 5: stacking the layers to produce a degradable flexible device;

[0123] Step 51, stacking and laying electrodes;

[0124] The magnesium electrode 10, the hydrogel electrolyte 20, and the molybdenum oxide electrode 30 are stacked in this order to obtain a sandwich structure, wherein the three should completely overlap after being stacked.

[0125] Step 52, setting the wire;

[0126] One end of a first molybdenum wire 11 is connected to the magnesium electrode 10 , and the other end of the first molybdenum wire 11 is exposed.

[0127] One end of a second molybdenum wire 31 is connected to the molybdenum oxide electrode 30 , and the other end of the second molybdenum wire 31 is exposed.

[0128] Step 53, packaging;

[0129] The laminated structure and the molybdenum wire coil 50 are wrapped and packaged with a PLGA flexible film 40, and the other end of the first molybdenum wire conductor 11 and the other end of the second molybdenum wire conductor 31 are exposed, thereby obtaining a degradable flexible device.

[0130] Performance Analysis

[0131] In Example 1, the magnesium electrode 10 in the prepared degradable flexible device is connected to a medical magnesium alloy bone screw (Mg-0.05Sr-0.5Nd) through the other end of the first molybdenum wire 11, and the other end of the second molybdenum wire 31 is exposed outside the PLGA flexible film.

[0132] In vitro degradation in PBS

[0133] See also Figure 3 As shown, the degradable flexible device prepared in Example 1 was placed in a PBS solution. The PLGA encapsulation degraded first, followed by the disintegration of the laminated structure. The magnesium electrode 10, hydrogel electrolyte 20, and molybdenum oxide electrode 30 in the laminated structure dissolved simultaneously. Except for the molybdenum oxide electrode 30, which completely disappeared after 60 days at a high temperature of 85 degrees Celsius, most of the magnesium electrode 10, hydrogel electrolyte 20, and PLGA membrane materials completely dissolved within 15 days. In simulated biological fluid (pH 7.4, 37°C), the dissolution rates of the Mg and Mo films were 1-10 μm / day and 0.02 μm / day, respectively.

[0134] Hydrogen release

[0135] See also Figure 4As shown, Example 1 and Sample B were placed in a phosphate-balanced physiological saline (PBS) solution in a sealed environment at a constant temperature of 37.5°C for 72 hours, and the amount of hydrogen released was recorded every 12 hours. The corrosion rates of Example 1 and Sample B can be characterized by the hydrogen release rate. Over the same time period, the amount of hydrogen released by Example 1 was 15.7% lower than that of Sample B. The significant reduction in hydrogen release rate indicates that the corrosion rate of Example 1 was suppressed.

[0136] NIH3T3 fibroblast cell culture and cytotoxicity assay results

[0137] The composition of the extract: The culture medium is prepared with DMEM culture medium and fetal bovine serum at a ratio of 9:1. The hydrogel electrolyte is sterilized under ultraviolet light for 4 hours and then placed in a sterile 6-well plate. The prepared culture medium is added according to a culture medium / sample mass ratio of 0.1g / mL, and the plate is placed in an incubator for leaching for 72 hours. The plate is then centrifuged twice to remove the precipitate in the extract. The centrifuge speed is set to 1000r / min. After removing the precipitate, the plate is filtered using a 0.22μm filter membrane and the extract stock solution is placed in a centrifuge tube. In addition, the extract stock solution is diluted with the prepared culture medium to a concentration of 50% and 25%, respectively, to obtain extracts of different concentrations of 100%, 50%, and 25%.

[0138] The cell morphology of NIH3T3 after co-culture with extracts of different materials and different concentrations for 2 days is shown in the figure Figure 5A 、 Figure 5B 、 Figure 5C As shown, the hydrogel electrolyte 20 exhibits good biocompatibility in different concentrations (100%, 50%, 25%) of leaching solution. Under different concentrations of leaching solution, the cells spread into a multi-layer spindle shape and the cell volume is normal, indicating that the cells can tolerate the corrosion degradation of the material.

[0139] The hydrogel electrolyte prepared in Example 1 was subjected to a 72-hour cytotoxicity test using the CCK-8 method. After cell culture, 10 μL of CCK-8 reagent was added to each well, followed by an additional 2 h of incubation in a 37°C CO2 incubator. The absorbance (OD) of the 96-well plate was then measured at 450 nm using a microplate reader, and the relative cell proliferation rate was calculated. The results showed that the prepared degradable flexible device had no toxicity to NiH3T3 cells. Figure 5D shown.

[0140] In vivo degradation

[0141] The flexible device prepared in Example 1 was implanted subcutaneously in rats. After 4 weeks, the PLGA film and the laminated structure degraded, and after 8 weeks, the flexible device was completely degraded.

[0142] Example 2 Slow degradation

[0143] Example 2 differs from Example 1 in that the resistance value of the oxidized molybdenum wire coil prepared in step 4 is selected. For a 0.1 mm diameter molybdenum wire, the resistance of the anodized molybdenum wire coil is 3000 ohms, and the coil length is 25 cm. Five turns are made on a 2 mm diameter loop. The PLGA powder ratio is 75% lactic acid and 25% glycolic acid.

[0144] Hydrogen release rate: The corrosion rate of Example 2 and Sample B can be characterized by the hydrogen release rate. Under the same time, the hydrogen release rate of Example 2 is 19.7% lower than that of Sample B. The hydrogen release rate is significantly reduced, indicating that the corrosion rate of Example 2 is suppressed. Figure 6 shown.

[0145] Example 3 Rapid degradation

[0146] Step 1, preparing a PLGA flexible film;

[0147] PLGA powder is a polylactic acid-glycolic acid copolymer with a ratio of 75% lactic acid and 25% glycolic acid.

[0148] Step 11: adding PLGA powder to ethyl acetate, ultrasonically mixing, and then magnetically stirring to obtain a uniform PLGA dispersion solution; wherein the mass concentration of PLGA powder in the PLGA dispersion solution is 30 g / L.

[0149] In step 12, the PLGA dispersion solution was spin-coated on the glass substrate at a spin-coating speed of 500 r / min, and then treated in a drying oven at 80° C. for 24 h to obtain a 250 μm thick PLGA flexible film as the encapsulation layer of the degradable flexible device.

[0150] Step 2: preparing the electrodes required for the degradable flexible device;

[0151] Step 21, preparing a molybdenum oxide electrode by anodization;

[0152] Molybdenum foil was ultrasonically treated in a 15% dilute hydrochloric acid solution for 5 minutes to remove the oxide layer formed on the surface of the foil. The foil was then cleaned with acetone, anhydrous ethanol, and then deionized water. Subsequently, the cleaned molybdenum foil was subjected to an electrochemical workstation (Zahner Elektrik IM6e, Germany) at a voltage of 1.0 V for 5 minutes to complete the anodic oxidation process, forming molybdenum oxide on the surface, thus preparing a molybdenum oxide electrode. The molybdenum foil dimensions were 10 × 10 × 0.2 mm.

[0153] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20KHz, treatment power is 1000W, and treatment temperature is 30℃.

[0154] Step 22, preparing a magnesium electrode;

[0155] Acetone, anhydrous ethanol, and deionized water were used to clean the magnesium foil in sequence. The cleaned magnesium foil was used as the magnesium electrode. The size of the magnesium foil was 10×10×0.2 mm.

[0156] Step 3, preparing an electrolyte for a degradable flexible device;

[0157] In step 31, 0.80 g of dipotassium hydrogen phosphate and 3.00 g of sodium dihydrogen phosphate were added to 1 L of deionized water, and the mixture was stirred evenly. Then, 50.0 g of sodium alginate powder was added and the mixture was stirred evenly to obtain an electrolyte solution.

[0158] In step 32, a 600 g / L calcium chloride solution is added to the electrolyte solution for calcium ion crosslinking, resulting in a sodium alginate hydrogel electrolyte with a thickness of 1 mm. The crosslinked hydrogel is a highly porous three-dimensional structure. This porous structure can store a large amount of electrolyte solution, ensuring the hydrogel's ionic conductivity.

[0159] Step 4, preparing a molybdenum oxide wire coil;

[0160] Molybdenum wire was ultrasonically treated in a 15wt% dilute hydrochloric acid solution for 5 minutes to remove the oxide layer on the wire surface. The wire was then cleaned with acetone, anhydrous ethanol, and deionized water, sequentially. Subsequently, the cleaned wire was anodic-oxidized in an electrochemical workstation (Zahner Elektrik IM6e, Germany) at 1.0V for 5 minutes, forming molybdenum oxide on the surface. This was then wound into a ring to produce a molybdenum oxide wire coil.

[0161] Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20KHz, treatment power is 1000W, and treatment temperature is 30℃.

[0162] The molybdenum wire used was 0.2mm in diameter and produced by Hunan Rare Earth Metal Materials Research Institute Co., Ltd. The anodized molybdenum wire coil had a resistance of 2500 ohms and a coil length of 25 cm. Eight turns were made around a diameter of 1 mm.

[0163] Step 5: stacking the layers to produce a degradable flexible device;

[0164] Step 51, stacking and laying electrodes;

[0165] The magnesium electrode 10, the hydrogel electrolyte 20, and the molybdenum oxide electrode 30 are stacked in this order to obtain a sandwich structure, wherein the three should completely overlap after being stacked.

[0166] Step 52, setting the wire;

[0167] One end of a first molybdenum wire 11 is connected to the magnesium electrode 10 , and the other end of the first molybdenum wire 11 is exposed.

[0168] One end of a second molybdenum wire 31 is connected to the molybdenum oxide electrode 30 , and the other end of the second molybdenum wire 31 is exposed.

[0169] Step 53, packaging;

[0170] The laminated structure and the molybdenum wire coil 50 are wrapped and packaged with a PLGA flexible film 40, and the other end of the first molybdenum wire conductor 11 and the other end of the second molybdenum wire conductor 31 are exposed, thereby obtaining a degradable flexible device.

[0171] Performance Analysis

[0172] In Example 3, the molybdenum oxide electrode 30 in the prepared degradable flexible device is connected to a medical magnesium alloy bone screw (Mg-0.05Sr-0.5Nd) through the other end of the second molybdenum wire 31, and the other end of the first molybdenum wire 11 is exposed outside the PLGA flexible film.

[0173] In vitro degradation in PBS

[0174] The degradable flexible device prepared in Example 3 was placed in a PBS solution. The PLGA encapsulation degraded first, followed by the disintegration of the laminated structure. The magnesium electrode 10, hydrogel electrolyte 20, and molybdenum oxide electrode 30 in the laminated structure dissolved simultaneously. Except for the molybdenum oxide electrode 30, which completely disappeared after 70 days at a high temperature of 65 degrees Celsius, most of the magnesium electrode 10, hydrogel electrolyte 20, and PLGA membrane materials completely dissolved within 15 days. In a simulated biological fluid (pH 7.4, 37°C), the dissolution rates of the Mg and Mo films were 1-10 μm / day and 0.02 μm / day, respectively.

[0175] Hydrogen release

[0176] See also Figure 7 As shown, Example 3 and Sample B were placed in a phosphate-balanced physiological saline (PBS) solution in a sealed environment at a constant temperature of 37.5°C for 72 hours, and the amount of hydrogen released was recorded every 12 hours. The corrosion rates of Example 1 and Sample B can be characterized by the hydrogen release rate. Over the same time period, the hydrogen release rate of Example 3 increased by 78.7% compared to that of Sample B. The significant increase in hydrogen release rate indicates that the corrosion rate of Example 3 has been significantly improved.

[0177] NIH3T3 fibroblast cell culture and cytotoxicity assay results

[0178] NIH3T3 cell morphology after 72 hours of co-culture with extracts of different materials and concentrations. Hydrogel electrolyte 20 exhibited good biocompatibility in various extract concentrations (100%, 50%, and 25%). In these extracts, the cells spread into a multilayered, spindle-shaped pattern with normal cell volume, demonstrating that the cells can tolerate the corrosive degradation of the material.

[0179] The composition of the extract: The culture medium is prepared with a ratio of DMEM culture medium to fetal bovine serum of 9:1. The hydrogel electrolyte is sterilized under ultraviolet light for 4 hours and then placed in a sterile 6-well plate. The prepared culture medium is added according to a culture medium / sample mass ratio of 0.1g / mL, and the plate is placed in an incubator for leaching for 72 hours. The plate is then centrifuged twice to remove the precipitate in the extract. The centrifuge speed is set to 1000r / min. After removing the precipitate, the plate is filtered using a 0.22μm filter membrane and the extract stock solution is placed in a centrifuge tube. In addition, the extract stock solution is diluted with the prepared DMEM culture medium to a concentration of 50% and 25%, respectively, to obtain extracts of different concentrations of 100%, 50%, and 25%.

[0180] The hydrogel electrolyte prepared in Example 3 was tested for cytotoxicity over a 72-hour period using the CCK-8 assay. After cell culture, 10 μL of CCK-8 reagent was added to each well, followed by an additional 2 hours of incubation in a 37°C CO2 incubator. The absorbance (OD) of the 96-well plate was measured at 450 nm using a microplate reader, and the relative cell proliferation rate was calculated. The results demonstrated that the prepared degradable flexible device was nontoxic to NiH3T3 cells.

[0181] Example 4 Rapid degradation

[0182] Example 4 differs from Example 3 in that the resistance value of the oxidized molybdenum wire coil prepared in step 4 is selected. For a molybdenum wire with a diameter of 0.1 mm, the resistance of the anodized molybdenum wire coil is 1000 ohms, and the coil length is 15 cm. Four turns are made on a diameter of 1 mm. The PLGA powder is prepared in a ratio of 50% lactic acid and 50% glycolic acid.

[0183] Hydrogen release rate: The corrosion rates of Example 4 and Sample B can be characterized by the hydrogen release rate. Under the same time, the hydrogen release rate of Example 4 is 82.6% higher than that of Sample B. The hydrogen release rate is significantly improved, indicating that the corrosion rate of Example 4 is significantly improved.

Claims

1. A method for preparing a degradable flexible device for regulating the degradation of medical magnesium alloy, characterized in that The following steps are included: Step 1, preparing a PLGA flexible film (40); Step 11, adding PLGA powder to an organic solvent, ultrasonically mixing, and then magnetically stirring to obtain a uniform PLGA dispersion solution; Wherein, the mass concentration of PLGA in the PLGA dispersion solution is 10 to 100 g / L; The organic solvent is chloroform, tetrahydrofuran or ethyl acetate; Step 12, spin coating the PLGA dispersion solution on the substrate at a spin coating speed of 500-1000 r / min, and then treating in a drying oven at 60-100° C. for 18-24 hours to obtain a PLGA flexible film (40); The thickness of the prepared PLGA flexible film (40) is 200 microns to 500 microns; The prepared PLGA flexible film (40) will be used as the encapsulation layer of the degradable flexible device; Step 2: preparing the electrodes required for the degradable flexible device; Step 21, preparing a molybdenum oxide electrode (30) by anodizing; The molybdenum foil is ultrasonically treated with a dilute hydrochloric acid solution for 3 to 10 minutes to remove the oxide layer formed on the surface of the molybdenum foil, and then cleaned with acetone, anhydrous ethanol, and deionized water in sequence; then, the clean molybdenum foil is anodized to form molybdenum oxide on the surface, thereby preparing a molybdenum oxide electrode (30), the molybdenum oxide electrode (30) having a thickness of 0.1 to 0.5 mm; The percentage concentration of dilute hydrochloric acid solution is 5 to 15; Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20-40KHz, treatment power is 500-2500W, and treatment temperature is 10℃-30℃; Anodic oxidation treatment process conditions: Molybdenum foil is set up in a three-electrode system, with the working electrode being molybdenum foil, the counter electrode being a platinum electrode, and the reference electrode being a saturated calomel electrode. A voltage of 0.8V to 1.5V is applied for 4min to 10min. Step 22, preparing a magnesium electrode 10; The magnesium foil is cleaned with acetone, anhydrous ethanol and deionized water in sequence to remove surface dirt to obtain a clean magnesium electrode (10), wherein the thickness of the magnesium electrode (10) is 0.1 to 0.5 mm; Step 3, preparing the electrolyte 20 for the degradable flexible device; Step 31, add 0.8-1.0 g of dipotassium hydrogen phosphate and 3.0-3.5 g of sodium dihydrogen phosphate to 1 L of deionized water, stir evenly, then add 30.0-50.0 g of sodium alginate powder, stir evenly to obtain an electrolyte solution; Step 32, adding calcium chloride solution to the electrolyte solution for calcium ion cross-linking to obtain a sodium alginate hydrogel electrolyte (20); The mass concentration of calcium chloride in the calcium chloride solution is 300-500 g / L; Step 4, preparing a molybdenum oxide wire coil (50); The molybdenum wire is ultrasonically treated with a dilute hydrochloric acid solution for 3 to 10 minutes to remove the oxide layer formed on the surface of the molybdenum wire, and then cleaned with acetone, anhydrous ethanol, and deionized water in sequence; then, the clean molybdenum wire is anodized to form molybdenum oxide on the surface, and is wound into a ring to obtain an oxide molybdenum wire coil (50); The percentage concentration of dilute hydrochloric acid solution is 5 to 15; Ultrasonic treatment process conditions: ultrasonic treatment frequency is 20-40KHz, treatment power is 500-2500W, and treatment temperature is 10-60℃; Anodic oxidation treatment process conditions: The molybdenum wire is set up in a three-electrode system, with the working electrode being molybdenum foil, the counter electrode being a platinum electrode, and the reference electrode being a saturated calomel electrode. A voltage of 0.8V to 1.5V is applied for 4min to 10min. Step 5: stacking the layers to produce a degradable flexible device; Step 51, stacking and laying electrodes; A magnesium electrode (10), a hydrogel electrolyte (20), and a molybdenum oxide electrode (30) are stacked in this order to obtain a sandwich structure, wherein the three electrodes should completely overlap after being stacked; Step 52, setting the wire; One end of a first molybdenum wire (11) is connected to the magnesium electrode (10), and the other end of the first molybdenum wire (11) is exposed; One end of a second molybdenum wire (31) is connected to the molybdenum oxide electrode (30), and the other end of the second molybdenum wire (31) is exposed; Step 53, packaging; The laminated structure and the molybdenum wire coil (50) are wrapped and packaged with a PLGA flexible film (40), and the other end of the first molybdenum wire conductor (11) and the other end of the second molybdenum wire conductor (31) are exposed, thereby obtaining a degradable flexible device.

2. The method for preparing a degradable flexible device for regulating the degradation of medical magnesium alloy according to claim 1, characterized in that: PLGA powder contains 50% lactic acid and 50% glycolic acid.

3. The method for preparing a degradable flexible device for regulating the degradation of medical magnesium alloy according to claim 1, characterized in that: PLGA powder contains 75% lactic acid and 25% glycolic acid.

4. The method for preparing a degradable flexible device for regulating the degradation of medical magnesium alloy according to claim 1, characterized in that: The diameter of molybdenum wire is 0.1~0.5mm.

5. The method for preparing a degradable flexible device for regulating the degradation of medical magnesium alloy according to claim 1, characterized in that: The resistance of the anodized molybdenum wire coil (50) is 1000 to 8000 ohms, and the coil length is 10 to 30 centimeters.

6. The degradable flexible device for regulating the degradation of medical magnesium alloys prepared by the method of claim 1, characterized in that: The invention comprises a magnesium electrode (10), a first molybdenum wire conductor (11), a hydrogel electrolyte (20), a molybdenum oxide electrode (30), a second molybdenum wire conductor (31) and a PLGA flexible film (40); the molybdenum wire length reserved on the second molybdenum wire conductor (31) is called a molybdenum oxide wire coil (50); the hydrogel electrolyte (20) is first placed between the magnesium electrode (10) and the molybdenum oxide electrode (30) to form a laminated structure; the laminated structure and the molybdenum wire coil (50) are then wrapped with the PLGA flexible film (40), and the other end of the first molybdenum wire conductor (11) and the other end of the second molybdenum wire conductor (31) are exposed; One end of the first molybdenum wire (11) is connected to the magnesium electrode (10); the other end of the first molybdenum wire (11) is connected to a magnesium alloy device implanted in a human body; or one end of the second molybdenum wire (31) is connected to the molybdenum oxide electrode (30); The other end of the second molybdenum wire (31) is connected to a magnesium alloy device implanted in the human body.

7. Application of the degradable flexible device prepared by the method of claim 1 in regulating medical magnesium alloys, characterized in that: The medical magnesium alloy device equipped with a degradable flexible device is called sample A during the degradation analysis process; The medical magnesium alloy device without the degradable flexible device is referred to as sample B during the degradation analysis process; the medical magnesium alloy device is connected to the magnesium electrode (10) in the degradable flexible device via the other end of the first molybdenum wire (11), which can reduce the corrosion rate of the medical magnesium alloy device, i.e., slow degradation; Comparison of degradation effects: Samples A and B were placed in a PBS solution and immersed in a sealed environment at a constant temperature of 37.5°C for 72 to 240 hours, and the amount of hydrogen released was recorded every 12 hours. The corrosion rates of samples A and B can be characterized based on the hydrogen release rate. During the same period of time, the hydrogen release of sample A was 15.7% to 20.0% lower than that of sample B.

8. Application of the degradable flexible device prepared by the method of claim 1 in regulating medical magnesium alloys, characterized in that: The medical magnesium alloy device equipped with a degradable flexible device is called sample A during the degradation analysis process; The medical magnesium alloy device without the degradable flexible device is referred to as sample B during the degradation analysis; The medical magnesium alloy device is connected to the anodic-oxidized molybdenum electrode (30) in the degradable flexible device through the other end of the second molybdenum wire (31), thereby increasing the corrosion rate of the medical magnesium alloy device, i.e., accelerating degradation; Comparison of degradation effects: Samples A and B were placed in a phosphate-balanced saline (PBS) solution in a sealed environment at a constant temperature of 37.5°C for 72 to 240 hours, and the amount of hydrogen released was recorded every 12 hours. The corrosion rates of samples A and B can be characterized based on the hydrogen release rate. Over the same period of time, the hydrogen release of sample A was 76.3% to 85.0% higher than that of sample B.

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