A wireless passive electrostimulating conductive degradable biological scaffold and its preparation method

Abstract

This application relates to a wireless passive electrostimulating conductive degradable biologic scaffold and its preparation method, belonging to the field of micro-nano 3D printing technology. First, design and prepare the structural model of the wireless passive electrostimulating conductive degradable biologic scaffold, prepare the biologic scaffold, conductify the biologic scaffold, the first coupling coil, print the isolation layer, and the encapsulation layer. The wireless power supply device is arranged outside the body. When the wireless power supply device is powered on, the second coupling coil excites a changing magnetic field by relying on the changing current, and the first coupling coil in the conductive biologic scaffold in the body performs wireless passive electrostimulation on cells. The degradable scaffold prepared in this application can achieve wireless passive electrostimulation in the body and is applicable to nerve cells, bone cells, cardiomyocytes, epidermal cells, etc.

Description

Technical Field

[0001] This application belongs to the technical field of micro-nano 3D printing, and particularly relates to a wireless passive electro-stimulating conductive degradable biologic scaffold and a preparation method thereof. Background Art

[0002] The emergence of tissue engineering has provided a brand-new solution for regenerative medicine such as repairing or replacing diseased or damaged tissues of the human body. With the continuous development of tissue engineering, as one of the most effective treatment means, biologic scaffolds present great application prospects in biomedicine. As a cell carrier, a biologic scaffold needs to simulate the extracellular matrix environment for cell survival as much as possible. On the one hand, it needs to have characteristics such as conforming to cell characteristic sizes, biocompatibility, biodegradability, and mechanical properties; on the other hand, since bioelectricity is an important characteristic for cells to maintain vitality and proliferation and differentiation, such as wound healing, muscle contraction, and nerve signal conduction, etc., all of which are affected and controlled by the bioelectricity existing in the human body, the conductivity of the biologic scaffold is also indispensable. Therefore, the preparation of conductive biologic scaffolds by 3D printing has become one of the research hotspots of biologic scaffolds at present.

[0003] A conductive biologic scaffold refers to a type of scaffold that is endowed with conductivity on the basis of a conventional biologic scaffold. With the conductivity of the biologic scaffold, the biologic scaffold can not only maintain cell phenotypes and simulate a highly biomimetic in vivo microenvironment, but also further apply electro-stimulation to the cells on the biologic scaffold to affect the growth and differentiation of the cells. For example, using a conductive biologic scaffold to connect damaged nerve tissues and as a propagation medium for electrical signals to make up for the deficiency of intercellular electrical communication, thereby being able to repair spinal cord injuries and nerve injuries; applying electro-stimulation to promote the growth, calcification, and synthesis of extracellular matrix of osteoblasts, which plays an important role in the repair of bone injuries; due to the electroactive characteristics of myocardial function, a conductive biologic scaffold can provide the physicochemical stimuli (electrical conductivity) required by cardiomyocytes, thereby controlling the proliferation and differentiation of cells and ultimately realizing tissue function.

[0004] Although 3D printed conductive scaffolds using carbon nanomaterials (graphene, carbon nanotubes) have been reported and used for cell culture at present. However, there is currently no wireless passive degradable 3D conductive biologic scaffold that can achieve effective in vivo electro-stimulation. Summary of the Invention

[0005] To solve the above problems, this application provides a wireless passive electro-stimulating conductive degradable biologic scaffold and a preparation method thereof.

[0006] In some embodiments of the application, a preparation method of a wireless passive electro-stimulating conductive degradable biologic scaffold is provided, including the following steps:

[0007] 1. Design the structural model of a wireless passive electrostimulating conductive degradable biocompatible scaffold and fabricate it: Draw the models of the biocompatible scaffold and the first coupling coil through software, convert the model files into printing path files, and import the path files into the printing software, and then perform the following steps:

[0008] 1.1 Select the printing substrate of the biocompatible scaffold, preprocess it to reduce the surface energy, and set it aside for later use;

[0009] 1.2 Print the degradable biocompatible scaffold: Select a biodegradable polymer as the printing material, and use the electric field-driven jet deposition micro-nano 3D printing technology to print the degradable biocompatible scaffold on the preprocessed substrate. Specifically, apply a voltage at the nozzle, and the printing material forms a Taylor cone at the nozzle outlet, generating a conical jet. The printing material is ejected downward from the nozzle under the action of the electric field, and a biocompatible scaffold with a preset pattern is printed on the substrate;

[0010] 1.3 Cover the surface of the biocompatible scaffold printed in step 1.2 with a conductive material to obtain a conductive degradable biocompatible scaffold;

[0011] 1.4 Select a biodegradable polymer as the printing material, and use the electric field-driven jet deposition micro-nano 3D printing technology to print an isolation layer on the conductive degradable biocompatible scaffold, and reserve two vertically interconnected through-holes on the isolation layer printed with the preset pattern;

[0012] 1.5 Pour a conductive polymer into the two reserved vertically interconnected through-holes to serve as a vertical interconnection circuit;

[0013] 1.6 Print the first coupling coil: Select a biodegradable conductive polymer as the printing material, and use the electric field-driven jet deposition micro-nano 3D printing technology to print a first coupling coil with a preset pattern on the basis of the printing product in step 1.5;

[0014] 1.7 Select a biodegradable polymer as the printing material, and use the electric field-driven jet deposition micro-nano 3D printing technology to print a packaging layer on the first coupling coil to obtain the wireless passive electrostimulating conductive degradable biocompatible scaffold.

[0015] In some embodiments of the present application, the biodegradable polymer in steps 1.2, 1.4, and 1.7 is polycaprolactone (PCL).

[0016] In some embodiments of the present application, the biodegradable conductive polymer in step 1.6 is PEDOT:PSS. PEDOT:PSS has good conductivity, and the electric energy generated by the coil inductance reaction can still meet the propagation of bioelectric signals through the conductive scaffold, providing sufficient electrical stimulation for cell growth and reproduction.

[0017] In some embodiments of the present application, the pretreatment of the substrate specifically includes: wiping the substrate clean with alcohol, then placing it in an ultrasonic cleaner and ultrasonically cleaning it with deionized water for 10 minutes, and finally drying the cleaned glass sheet and placing it on the printer platform.

[0018] In some embodiments of the present application, in step 1.2, after selecting the printing material, place the printing material in a beaker, and place the beaker in a drying oven to dry for 2 hours to remove the moisture in the material and avoid affecting the viscosity of the material; then place the printing material in a material bucket and heat it to the set temperature value to completely melt the material; print a biological scaffold with a preset pattern on the substrate.

[0019] In some embodiments of the present application, in step 1.4, two electrode holes are preset in the printed isolation layer, and conductive liquid is poured into the holes until it is flush with the holes.

[0020] In some embodiments of the present application, in step 1.3, the covering method is to select a conductive material solution with the opposite polarity to the printing voltage, coat the surface of the scaffold, and through the electrostatic attraction between the charged biological scaffold and the conductive material, make the conductive material evenly wrap on the surface of the biological scaffold, so as to obtain a conductive biological scaffold with high conductivity.

[0021] In some embodiments of the present application, in step 1.1, the substrate includes, but is not limited to, insulating hard materials such as glass sheets and ceramics.

[0022] In some embodiments of the present application, in step 1.6, after selecting the printing material, place the printing material in a beaker, and place the beaker in a drying oven to dry for 2 hours to remove the moisture in the material and avoid affecting the viscosity of the material; then place the printing material in a material bucket and heat it to the set temperature value to completely melt the material; print a first coupling coil with a preset pattern on the substrate.

[0023] In some embodiments of the present application, before coating the conductive material, it further includes: peeling the printed biological scaffold from the substrate, trimming the biological scaffold, and then using absolute ethanol to perform surface hydrophilic treatment on the biological scaffold so that the conductive material can better wrap on the surface of the biological scaffold, and then coating the surface of the scaffold with the conductive material.

[0024] In some embodiments of the present application, the electrohydrodynamic jet deposition micro-nano 3D printing technology is adopted, an electric field is applied, so that under the action of the electric field force, the printing material forms a Taylor cone jet at the nozzle outlet, and the material deposits a filament with a line width much smaller than the inner diameter of the nozzle on the substrate in the form of a cone jet, and the substrate is not grounded to the electrode.

[0025] In some embodiments of the present application, in step 1.2, multi-layer printing and superposition are adopted to print a multi-layer biological scaffold, and a biological scaffold with a 3D network structure of a certain height is obtained.

[0026] In some embodiments of the present application, in step 1.3, the concentration of the conductive material solution is 4-10 mg / ml; the conductive materials include but are not limited to conductive materials such as MXene, carbon nanotubes, graphene, and graphene oxide.

[0027] In some embodiments of the present application, in step 1.3, through different numbers of coatings of the conductive material, the thickness of the coating layer can reach about 10 nm - 2 μm, and the coated biological scaffold has good conductivity.

[0028] In some embodiments of the present application, in step 1.3, the conductive material is MXene.

[0029] In some embodiments of the present application, the MXene has a large specific surface area and rich surface functional groups. There are hydroxyl groups or terminal oxygen on the surface of MXene, and it has the metallic conductivity of transition metal carbides.

[0030] In some embodiments of the present application, the MXene is an aqueous solution of single-layer Ti3C2 after etching.

[0031] In some embodiments of the present application, in step 1.6, the conductive material is PEDOT:PSS, and the PEDOT:PSS is an aqueous solution of a polymer and has a high conductivity.

[0032] In some embodiments of the present application, the material for printing the first coupling coil is PEDOT:PSS.

[0033] In some embodiments of the present application, the concentration of the PEDOT:PSS aqueous solution is 5-7 wt%.

[0034] In some embodiments of the present application, by adjusting the voltage, air pressure, nozzle temperature, barrel temperature, printing speed, distance between the nozzle and the substrate, etc. during the printing process, the line width, period, and height of the printed scaffold are regulated to obtain a scaffold of the required size.

[0035] In some embodiments of the present application, the designed biodegradable scaffold has a line width of 10-20 μm, a period of 1-100 μm, 5-20 layers, and a thickness of 30-125 μm.

[0036] In some embodiments of the present application, the printing speed is 5-10 mm / s, the air pressure is 15-20 kPa, the printing voltage is 1500 V, and the distance between the nozzle and the substrate is 200-250 μm.

[0037] In some embodiments of the present application, the designed isolation layer has a line width of 20 - 500 μm, a period of 1 - 500 μm, 1 - 100 layers, a thickness of 20 - 500 μm, and two through holes with dimensions of 10 - 100 μm are reserved.

[0038] In some embodiments of the present application, the designed encapsulation layer has a line width of 20 - 500 μm, a period of 1 - 500 μm, 1 - 100 layers, and a thickness of 200 - 500 μm.

[0039] In some embodiments of the present application, the first coupling coil has a square structure, the area of the coil can reach 10 mm * 10 mm - 50 mm * 50 mm, the line width is 0.5 - 1 mm, and the printed first coupling coil has good conductivity.

[0040] In some embodiments of the present application, to meet the performance requirements of the coupling coil, the number of turns of the coil is 9 - 12.

[0041] In some embodiments of the present application, for coils of different sizes, different inductance values are obtained after the number of turns reaches different numbers.

[0042] In some embodiments of the present application, a wireless passive electro - stimulation conductive degradable biologic scaffold prepared by the above method is also provided.

[0043] In some other embodiments of the present application, a wireless passive electro - stimulation device is also provided, which includes a wireless passive electro - stimulation conductive degradable biologic scaffold prepared by the above preparation method and a wireless power supply device.

[0044] In some embodiments of the present application, the wireless power supply device includes the following steps:

[0045] 2. Design the structural model of the wireless power supply device and prepare the wireless power supply device: Draw the model of the wireless power supply device through software, convert the model file into a printing path file, and import the path file into the printing software, and then perform the following steps:

[0046] 2.1 Print the housing of the wireless power supply device: Select the printing substrate of the wireless power supply device, select the housing printing material, and use 3D printing technology to print the housing of the wireless power supply device on the substrate. A position for placing the second coupling coil and the circuit board is reserved inside the housing of the wireless power supply device;

[0047] 2.2 Printing of the second coupling coil:

[0048] Select a conductive paste as the printing material and use the electric field-driven jet deposition micro-nano 3D printing technology to print the second coupling coil with the conductive paste at the reserved position for placing the second coupling coil. Specifically, apply a voltage at the nozzle, and the printing material forms a Taylor cone at the nozzle outlet, generating a conical jet. Under the action of the electric field, the printing material is ejected downward from the nozzle, and a second coupling coil with a preset pattern is printed on the substrate.

[0049] In some embodiments of the present application, the 3D printing technology adopted in step 2.1 is fused deposition modeling (FDM).

[0050] In some embodiments of the present application, the conductive paste is a conductive silver paste, a conductive copper paste or other conductive pastes.

[0051] In some embodiments of the present application, the printing material is ABS plastic.

[0052] In some embodiments of the present application, the designed wireless power supply device is a square structure, and the area of the device can reach about 20mm * 20mm - 100mm * 100mm.

[0053] In some embodiments of the present application, the substrate is an insulating hard material.

[0054] In some embodiments of the present application, the substrate can be pretreated in step 2.1 by using the same method as the substrate pretreatment in step 1.1.

[0055] Compared with the prior art, the present application has at least the following advantages:

[0056] 1. For common 3D printing technologies such as electrospinning, electrohydrodynamic jet printing, stereolithography, etc., the polymer printing material is melted at high temperature during the printing process, and the diameter of the printed fiber is relatively thick, which seriously affects the effect of cell culture and the efficiency of intercellular information conduction after being implanted into the organism. The present application adopts the electric field-driven jet deposition micro-nano 3D printing technology. Under the action of back pressure and its own gravity, the molten printing material forms a meniscus shape at the printing nozzle. Connect the nozzle to a high-voltage power supply to make the meniscus material charged. Under the action of the electric field force, the material overcomes the surface tension, forms a Taylor cone, and deposits on the substrate. Then, by optimizing the process parameters, the Taylor cone is stabilized, and the material is ejected from the nozzle to form an extremely fine conical jet. The printing platform runs according to the specified program, enabling the material to be accurately deposited on the substrate to prepare a highly ordered three-dimensional biological scaffold.

[0057] 2. The present application uses a biological scaffold composite coupling coil to achieve wireless and passive operation of the biological scaffold when placed in the body.

[0058] 3. The biodegradable conductive polymer is used as the printing material of the coupling coil, especially PEDOT:PSS, which avoids the problems caused by the ineffective degradation of the coupling coil in the body and the resulting repulsion in the body.

[0059] 3. The coupling coil is printed with PEDOT:PSS conductive material. By varying the size of the coil, the size of the inductance coil can reach about 10mm*10mm - 50mm*50mm, and the diameter is about 1 - 2mm. The coupling coil printed with PEDOT:PSS material has good inductance effect.

[0060] 4. Coupling coils with different sizes and different numbers of turns can obtain different inductance values, and the stent still has good inductance effect after using PEDOT:PSS as the printing material. Description of the Drawings

[0061] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present application. For those skilled in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0062] Figure 1 It is a schematic diagram of the wireless power supply device of the present application.

[0063] Figure 2 It is a schematic diagram of the coupling coil of the present application.

[0064] Figure 3 It is a schematic diagram of the operation steps for preparing the wireless passive electrostimulating conductive biodegradable stent of the present application. Detailed Embodiments

[0065] The following will clearly and completely describe the technical solutions of the present application in conjunction with the drawings and specific embodiments. However, those skilled in the art will understand that the following described embodiments are some embodiments of the present application, rather than all embodiments, and are only used to illustrate the present application and should not be regarded as limiting the scope of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present application. For those embodiments where specific conditions are not indicated, they are carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments where the manufacturer is not indicated, they are all conventional products that can be obtained through commercial purchase.

[0066] The applicant innovatively found that the conductive biostent can be combined with the wireless power transmission technology based on the magnetic field coupling principle, i.e., inductive coupling power transmission, to achieve the effect of wireless passive electrostimulation.

[0067] The wireless power supply device can be arranged outside the body. When the wireless power supply device is powered on, the second coupling coil excites a changing magnetic field by relying on the changing current, completing the conversion of electrical energy into magnetic energy. The first coupling coil in the conductive biological scaffold in the body picks up electrical energy from the spatially changing magnetic field to perform wireless passive electrical stimulation on cells. Therefore, the electrically stimulative conductive degradable scaffold based on wireless charging can achieve wireless passive electrical stimulation in the body and can be applicable to nerve cells, bone cells, myocardial cells, epidermal cells, etc.

[0068] A wireless passive electrical stimulation device includes a wireless passive electrical stimulation conductive degradable biological scaffold and a wireless power supply device.

[0069] In some embodiments of the present application, the first coupling coil is further described by taking the PEDOT:PSS conductive polymer as an example.

[0070] After designing the biological scaffold and the first coupling coil model, add the printing material to the storage barrel for preheating. After heating to the molten state, apply air pressure to extrude the material to the nozzle at a higher temperature, so that the material changes from the molten state to an easily ejectable state. By adjusting the nozzle temperature and the air pressure magnitude, make the surface tension of the material balance with its own gravity and the pressure applied by the air pressure, and the material forms a meniscus shape at the nozzle. Connect the positive electrode of the high-voltage DC power supply to the nozzle, turn on the power supply to make the meniscus at the nozzle carry a positive charge, so that the printed material carries a positive charge. Under the action of the electric field force, the meniscus is gradually stretched to form a Taylor cone, so that the material is deposited on the substrate. Through a series of experiments to optimize the printing parameters, make the ejected Taylor cone accurately deposit on the substrate. After printing the first layer, the nozzle is lifted up a certain height. Due to the height lift, the electric field force generated by the applied electric field decreases. Therefore, when printing multiple layers of biological scaffolds, the voltage increases with the increase of the lift height, so that the printing material can be accurately stacked layer by layer to realize printing a three-dimensional highly ordered biological scaffold.

[0071] Then use MXene for coating. Due to its large specific surface area and rich surface functional groups (such as hydroxyl groups or terminal oxygen), it has metal conductivity similar to that of transition metal carbides. Coating on the surface of the biological scaffold can make the scaffold obtain conductivity.

[0072] Then, on the biological scaffold, use the PEDOT:PSS conductive polymer to print the first coupling coil, which has metal conductivity similar to that of a copper coil. Adopting the principle of electromagnetic induction, energy transfer is realized through the coil for energy coupling. Print a non-conductive isolation layer on the first coupling coil. Both ends of the coupling coil are perpendicularly connected to the conductive biological scaffold through the through holes of the isolation layer, and a conductive solution is poured into the through holes as the two end electrodes, so that the scaffold can perform passive electrical stimulation.

[0073] In some embodiments of the present application, the housing of the wireless power supply device is designed to be square according to the shape of the coil, with grooves for placing the coil and the circuit board and spaces for the jacks of the socket left. The schematic diagram is as shown in Figure 1 shown.

[0074] In another embodiment of the present application, the structural models of the biological scaffold and the coupling coil are designed as follows: draw the two-dimensional model of the device through AutoCAD, convert the model file into a printing path file, and import the path file into the printing software. Then, perform the following steps:

[0075] 1. Select a glass slide as the substrate. Scrub the substrate clean with alcohol, then place it in an ultrasonic cleaner and ultrasonically clean it with deionized water for 10 minutes. Finally, dry the cleaned glass slide and place it on the printer platform.

[0076] 2. Select polycaprolactone (PCL) as the printing material. Dry the printing material, place the dried printing material in a material bucket, install a heating device and a nozzle, set the temperature of the material bucket to 90 °C and the temperature of the nozzle to 100 °C, and wait for the material to completely melt. Use a Musashi nozzle with an inner diameter of 150 μm for the nozzle. Connect the positive pole of the high-voltage DC power supply to the nozzle, and connect the air compressor air pipe to the mouth of the material bucket to complete the installation of the printing equipment. Adjust the parameters of the printer: voltage 1.5 kV; air pressure 15 kPa; printing speed 300 mm / min; distance between the nozzle and the substrate 0.2 mm, and start printing. The printing material is steadily extruded and deposited on the glass slide substrate. After printing 8 layers, a biological scaffold with a thickness of about 50 μm, a period of 60 μm, and a line width of 12 μm is obtained.

[0077] 3. Select the etched single-layer Ti3C2 aqueous solution as the coating material. First, perform a hydrophilic treatment on the biological scaffold with absolute ethanol. After drying, coat the biological scaffold with the etched Ti3C2 aqueous solution and let it stand for 10 minutes until it dries. Repeat the operation 6 times to obtain a conductive biological scaffold with a good conductive effect.

[0078] 4. Select polycaprolactone (PCL) as the printing material. Dry the printing material and put the dried printing material into the hopper. Install the heating device and the nozzle. Set the hopper temperature at 90 °C and the nozzle temperature at 100 °C, and wait for the material to melt completely. Use a Musashi nozzle with an inner diameter of 150 μm for the nozzle. Connect the positive pole of the high-voltage DC power supply to the nozzle. Connect the air compressor air pipe to the hopper opening to complete the installation of the printing equipment. Adjust the parameters of the printer: voltage 1.5 kV; air pressure 15 kPa; printing speed 300 mm / min; distance between the nozzle and the substrate 0.2 mm. Start printing. The printing material is steadily extruded and deposited on the biological scaffold. After printing 30 layers, an isolation layer with a thickness of about 200 μm, a period of 100 μm, and a line width of 200 μm is obtained, and through holes with a diameter of 50 μm are reserved for the vertical interconnection of the first coupling coil and the conductive scaffold. Select the Ti3C2 aqueous solution as the conductive liquid and pour the conductive liquid into the through holes.

[0079] 5. Select PEDOT:PSS conductive polymer as the printing material. The concentration of PEDOT:PSS nanofibers is 5 wt%. Dry the printing material and put the dried printing material into the hopper. Install the heating device and the nozzle. Set the hopper temperature at 90 °C and the nozzle temperature at 100 °C, and wait for the material to melt completely. Use a Musashi nozzle with an inner diameter of 150 μm for the nozzle. Connect the positive pole of the high-voltage DC power supply to the nozzle. Connect the air compressor air pipe to the hopper opening to complete the installation of the printing equipment. Adjust the parameters of the printer: voltage 1.5 kV; air pressure 15 kPa; printing speed 300 mm / min; distance between the nozzle and the substrate 0.2 mm. Start printing. The printing material is steadily extruded and deposited on the wireless power supply device scaffold. After printing 1 layer, a coupling coil with a wire diameter of about 1 mm, 11 turns, and a length and width of 50 mm * 50 mm is obtained.

[0080] 6. Select polycaprolactone (PCL) as the printing material. Dry the printing material and put the dried printing material into the hopper. Install the heating device and the nozzle. Set the hopper temperature at 90 °C and the nozzle temperature at 100 °C, and wait for the material to melt completely. Use a Musashi nozzle with an inner diameter of 150 μm for the nozzle. Connect the positive pole of the high-voltage DC power supply to the nozzle. Connect the air compressor air pipe to the hopper opening to complete the installation of the printing equipment. Adjust the parameters of the printer: voltage 1.5 kV; air pressure 15 kPa; printing speed 300 mm / min; distance between the nozzle and the substrate 0.2 mm. Start printing. The printing material is steadily extruded and deposited on the first coupling coil. After printing 30 layers, a thin layer with a thickness of about 200 μm, a period of 100 μm, and a line width of 200 μm is obtained and used as the encapsulation layer.

[0081] The wireless passive electro-stimulating conductive degradable biologic scaffold prepared by the preparation method of the present application has a good three-dimensional structure and a high degree of freedom in space, providing more possibilities for the survival and growth of cells.

[0082] In some embodiments of the present application, the wireless power supply device includes the following steps:

[0083] 2. Design the structural model of the wireless power supply device and prepare the wireless power supply device: Draw the model of the wireless power supply device through software, convert the model file into a printing path file, and import the path file into the printing software, and then perform the following steps:

[0084] 2.1 Print the outer shell of the wireless power supply device: Select the printing substrate of the wireless power supply device, select the outer shell printing material, and use 3D printing technology to print the outer shell of the wireless power supply device on the substrate. A position for placing the second coupling coil and the circuit board is reserved inside the outer shell of the wireless power supply device;

[0085] 2.2 Printing of the second coupling coil:

[0086] Select conductive silver material as the printing material, and use the electric field-driven jet deposition micro-nano 3D printing technology to print the second coupling coil at the reserved position for placing the second coupling coil with conductive paste. Specifically, apply a voltage at the nozzle, the printing material forms a Taylor cone at the nozzle outlet, generating a conical jet, and the printing material is ejected downward from the nozzle under the action of the electric field to print the second coupling coil with a preset pattern on the substrate.

[0087] In some embodiments of the present application, the 3D printing technology used in step 2.1 is fused deposition modeling (FDM).

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not intended to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the various embodiments of the present application.

Claims

1. A preparation method of a wireless passive electro-stimulating conductive degradable biological scaffold, characterized by comprising the following steps: First, design and prepare a structural model of a wireless passive electro-stimulating conductive degradable biological scaffold: draw the models of the biological scaffold and the first coupling coil through software, convert the model files into printing path files, and import the path files into the printing software, and then perform the following steps: 1.1 Select the printing substrate of the biological scaffold and pre-treat it for standby; 1.2 Degradable biological scaffold printing: Select a biodegradable polymer as the printing material and use the electric field-driven jet deposition micro-nano 3D printing technology to print a degradable biological scaffold on the pre-treated substrate. Specifically, apply a voltage at the nozzle, and the printing material forms a Taylor cone at the nozzle outlet, generating a conical jet. The printing material is ejected downward from the nozzle under the action of the electric field to print a biological scaffold with a preset pattern on the substrate; 1.3 Cover the surface of the biological scaffold printed in step 1.2 with a conductive material to obtain a conductive degradable biological scaffold; 1.4 Select a biodegradable polymer as the printing material and use the electric field-driven jet deposition micro-nano 3D printing technology to print an isolation layer on the conductive degradable biological scaffold, and reserve through holes on the isolation layer with a preset pattern; 1.5 Pour a conductive polymer into the reserved through holes to serve as an interconnection circuit; 1.6 First coupling coil printing: Select a biodegradable conductive polymer as the printing material and use the electric field-driven jet deposition micro-nano 3D printing technology to print a first coupling coil with a preset pattern on the basis of the printing product in step 1.5; 1.7 Select a biodegradable polymer as the printing material and use the electric field-driven jet deposition micro-nano 3D printing technology to print a packaging layer on the first coupling coil to obtain the wireless passive electrostimulating conductive degradable biological scaffold.

2. The preparation method of a wireless passive electrostimulating conductive degradable biologic scaffold according to claim 1, wherein The biodegradable polymers in steps 1.2, 1.4, and 1.7 are all polycaprolactone (PCL), or the biodegradable polymers in steps 1.2, 1.4, and 1.7 are different or not completely the same; the biodegradable conductive polymer in step 1.6 is PEDOT:PSS.

3. The preparation method of a wireless passive electro-stimulating conductive degradable biological scaffold according to claim 1, wherein, In step 1.2, after selecting the printing material, put the printing material into a beaker and place the beaker in a drying oven for 2 hours to remove the moisture in the material and avoid affecting the viscosity of the material; then put the printing material into a material barrel and heat it to the set temperature value to completely melt the material; print a biological scaffold with a preset pattern on the substrate.

4. The preparation method of a wireless passive electrostimulating conductive degradable biologic scaffold according to claim 1, wherein In step 1.4, two electrode holes are preset in the printed isolation layer, and a conductive liquid is poured into the holes until it is flush with the holes.

5. The preparation method of a wireless passive electro-stimulating conductive degradable biological scaffold according to claim 4, characterized in that, The electrode holes are perpendicular to the biological scaffold.

6. The preparation method of a wireless passive electro-stimulating conductive degradable biologic scaffold according to claim 1, characterized in that The covering method in step 1.3 is to select a conductive material solution with the opposite polarity of the printing voltage, coat the surface of the biological scaffold, and make the conductive material uniformly wrap on the surface of the biological scaffold through the electrostatic attraction between the charged biological scaffold and the conductive material, so as to obtain a conductive biological scaffold.

7. The preparation method of a wireless passive electro-stimulating conductive degradable biological scaffold according to claim 1, wherein In step 1.2, multi-layer printing superposition is adopted to print multi-layer biological scaffolds to obtain a biological scaffold with a 3D network structure of a certain height; in step 1.3, the concentration of the conductive material solution is 4-10 mg / ml; the conductive material includes an MXene material, and the MXene is an aqueous solution of etched single-layer Ti3C2.

8. The preparation method of a wireless passive electrostimulating conductive degradable biological scaffold according to claim 1, characterized in that, The designed biodegradable stent has a line width of 10 - 20 μm, a period of 1 - 100 μm, 5 - 20 layers, and a thickness of 30 - 125 μm; the designed isolation layer has a line width of 20 - 500 μm, a period of 1 - 500 μm, 1 - 100 layers, and a thickness of 20 - 500 μm, and two through holes with sizes of 10 - 100 μm are reserved; the designed encapsulation layer has a line width of 20 - 500 μm, a period of 1 - 500 μm, 1 - 100 layers, and a thickness of 200 - 500 μm.

9. A wireless passive electrostimulating conductive degradable biological scaffold, characterized in that, It is prepared by the preparation method of a wireless passive electrostimulating conductive biodegradable biological stent according to any one of claims 1 - 8.

10. A wireless passive electrical stimulation device, characterized in that, It includes the wireless passive electrostimulating conductive biodegradable biological stent according to claim 9 and a wireless power supply device.

11. A wireless passive electrical stimulation device according to claim 10, characterized in that, The said wireless power supply device includes the following steps: First, design the structural model of the wireless power supply device and prepare the wireless power supply device: draw the model of the wireless power supply device through software, convert the model file into a printing path file, and import the path file into the printing software, and then perform the following steps: 2.1 Print the shell of the wireless power supply device: Select the printing substrate of the wireless power supply device, select the shell printing material, and use 3D printing technology to print the shell of the wireless power supply device on the substrate. A position for placing the second coupling coil and the circuit board is reserved inside the shell of the wireless power supply device; 2.2 Printing of the second coupling coil: Select the conductive paste as the printing material, and use the electric - field - driven jet - deposition micro - nano 3D printing technology to print the second coupling coil at the reserved position for placing the second coupling coil with the conductive paste. Specifically, apply a voltage at the nozzle, the printing material forms a Taylor cone at the nozzle outlet, generates a conical jet, and the printing material is ejected downward from the nozzle under the action of the electric field to print the second coupling coil with a preset pattern on the substrate.

Images