A solution bath near-field cell 3D printing molding device and molding method thereof
By using a solution-bath near-field cell 3D printing molding device in cell 3D printing technology, the electric field force of the low-voltage near-field module is used to quickly gel the cell ink in the electrolyte solution, solving the problems of low accuracy and low cell survival in the prior art, and achieving high-precision and efficient cell 3D printing.
Patent Information
- Application Number
- CN202011218113.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2020-11-04
- Publication Date
- 2025-05-16
- Estimated Expiration
- 2040-11-04
AI Technical Summary
The existing 3D printing technology of cells has problems such as low accuracy and low cell survival.
A solution bath near-field cell 3D printing molding device is used, which includes a near-field module, an extrusion-control module and a solution bath collection module. The low-voltage near-field module generates an electric field force, so that the cell ink is pulled into a wire under the action of the electric field, and quickly gels in the electrolyte solution to achieve high-precision 3D printing of cells.
It improves the accuracy of cell 3D printing, the printing accuracy can reach 10μm, and improves cell survival and cell density, achieving more efficient cell 3D printing performance.
Smart Images

Figure CN112477110B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of cell 3D printing, and in particular relates to a solution bath near-field cell 3D printing molding device and a molding method thereof. Background Art
[0002] The structural unit in the human body that is composed of multiple tissues and can perform certain or specific functions is called an organ. Diseases, congenital malformations, traffic accidents and other reasons have caused a large number of tissue and organ defects, which has also created a huge demand for tissue and organ repair in society. Tissue and organ repair can be divided into biological prostheses and artificial prostheses according to the source of the prosthesis. Biological prostheses can be divided into three types, namely, allogeneic prostheses, allogeneic prostheses and xenogeneic prostheses. Allogeneic prostheses obtain transplant donors from the patient's own body. Its biggest advantage is that it can avoid immune rejection, but it requires the transplant to be cut from a healthy part, its source is limited, and it will also cause secondary damage. Allogeneic prostheses are donors and recipients of the same species, often from donors, but they face a certain risk of immune rejection and have limited sources. The donor and recipient of xenogeneic prostheses do not belong to the same species, and their source is wide, but their risk of immune rejection is greater. Since the above-mentioned repair methods cannot meet the needs, artificial prostheses are born. However, artificial replacement materials do not have biological characteristics and it is difficult to meet the real clinical treatment requirements. The emergence of tissue engineering theory and technology in the past 20 years has shown new hope in the repair and reconstruction of tissues and organs, and the provision of biologically active transplants.
[0003] Tissue engineering refers to the application of the principles and methods of life science and engineering science to study or develop human organ and tissue substitutes to replace part or all of the functions of organs or tissues. It involves the cross-integration of a series of disciplines such as clinical medicine, biomaterials, cell biology, molecular biology, and bioengineering, and can be divided into two types: cellular and non-cellular. In recent years, tissue engineering has made remarkable achievements. As the forefront of the development of medical science, its great scientific significance and attractive clinical applications have made some important progress. In addition, the development of bioregenerative technology has injected fresh blood into tissue engineering. The development of new technologies represented by cell printing has made it possible to construct living tissues and organs in vitro.
[0004] In 3D cell printing technology, biomaterials, biochemicals and living cells as well as functional components are precisely positioned layer by layer and placed in space to manufacture 3D structures. 3D cell printing is mainly divided into inkjet, micro-extrusion and laser-assisted printing. Inkjet printing is the most commonly used type of printing for non-biological and biological applications. It is formed by controlling the delivery of liquid to a predetermined location. Inkjet printing has the advantages of fast printing speed, low cost and wide application range. However, the risk of cells and materials being exposed to thermal and mechanical stress, low droplet directionality, uneven droplet size, frequent nozzle clogging and unreliable cell encapsulation bring considerable disadvantages to the application of inkjet printing in 3D bioprinting. Micro-extrusion bioprinting is usually composed of a temperature-controlled material handling and dispensing system and a workbench. Its printing inks include hydrogels, biocompatible copolymers and cell spheroids. Its main advantage is the ability to deposit very high cell density. Achieving physiological cell density in tissue engineering organs is the main goal in the field of bioprinting. However, due to the shear stress it exerts on cells in viscous fluids, the cell survival rate is low (between 40 and 86%). Laser-assisted bioprinting is based on the principle of laser-induced forward transfer. Laser-induced forward transfer technology was originally used to transfer metals and has now been successfully applied to transfer biomaterials such as peptides, DNA, and cells. Because laser-assisted bioprinting is nozzle-free, the problem of cell or material clogging is avoided. Laser-assisted bioprinting has the advantages of good viscosity compatibility, fast printing speed, and high cell deposition density. However, it is expensive and not suitable for printing multiple materials at the same time.
[0005] High-voltage electrospinning technology is a method of preparing nano-micron fiber materials by using the breakdown effect of high-voltage electrostatic fields on polymer solutions. It can easily prepare one-dimensional fibers at the micro and nano scales and is widely used in the preparation of various nanofibers. However, electrospinning often cannot accurately control the spatial location of the ink, which limits its ability to form three-dimensional products. Summary of the invention
[0006] In order to improve the current problems of cell 3D printing technology such as low precision and low cell survival rate, the present invention provides a solution bath near-field cell 3D printing molding device and a molding method thereof.
[0007] The present invention provides the following technical solutions:
[0008] A solution bath near-field cell 3D printing molding device, comprising a near-field module, an extrusion-control module and a solution bath collection module;
[0009] The extrusion-control module is arranged above the solution bath collection module;
[0010] The near-field module is disposed between the extrusion-control module and the solution bath collection module, and the near-field module is connected to the extrusion-control module and the solution bath collection module respectively;
[0011] The solution bath collection module includes an insulating container, an electrolyte solution contained in the insulating container, and a deposition platform immersed in the electrolyte solution.
[0012] According to an embodiment of the present invention, the extrusion-control module includes a print head and a pneumatic extrusion control module, and the print head is connected to the bottom end of the pneumatic extrusion control module.
[0013] According to an embodiment of the present invention, the number of print heads can be at least 1, for example, 2, 3, 4 or more print heads can be set; optionally, when multiple print heads are set, coaxial print heads or non-coaxial print heads can be selected. For example, a temperature adjustment module can be optionally set on one or more print heads, and the setting of the temperature adjustment module can achieve -10 to 260 ° C adjustment, and the printing of different cell inks can be satisfied by adjusting the temperature. For another example, the extrusion-control module can optionally set one or more coaxial print heads, and the inner channel and outer channel of the coaxial print head can print different cell inks.
[0014] According to an embodiment of the present invention, the diameter of the print head can be 0.3mm-1mm, for example, the diameter is 0.4mm, 0.6mm or 0.8mm. Further, for a coaxial print head, its inner diameter can be 0.15mm-1.5mm, and its outer diameter can be 0.3mm-2mm, for example, the inner diameter is 0.51mm and the outer diameter is 0.82mm. For example, the material of the print head can be a biocompatible conductive metal material, such as medical stainless steel.
[0015] According to an embodiment of the present invention, the pneumatic extrusion control module includes a gas inlet and a cell ink containing chamber. The cell ink is extruded and the flow rate and stop of the cell ink can be controlled by adjusting the air pressure of the gas inlet. The cell ink is a low-viscosity cell ink, for example, the cell ink can use at least one of sodium alginate, silk fibroin, collagen, etc., for example, sodium alginate.
[0016] According to an embodiment of the present invention, the material of the pneumatic extrusion control module can be selected from biologically inert insulating materials, such as biocompatible PP (polypropylene) material and the like.
[0017] According to an embodiment of the present invention, the distance between the print head of the extrusion-control module and the liquid surface where the electrolyte solution contacts the air is 0.5-40 mm, for example, 1-15 mm, 3-10 mm, 5-8 mm.
[0018] According to an embodiment of the present invention, the near-field module is arranged on a side close to the print head. The near-field module can be a high-voltage near-field module or a low-voltage near-field module, preferably a low-voltage near-field module; further, the voltage of the low-voltage near-field module can be 0.1 to 10 kV, such as 0.5 to 8 kV, 1 to 7 kV, or 3 to 5 kV.
[0019] According to an embodiment of the present invention, the near-field module comprises a positive electrode and a negative electrode, the positive electrode is electrically connected to the print head, and the negative electrode extends into the electrolyte solution in the insulating container.
[0020] According to the embodiment of the present invention, the shape of the insulating container is not particularly limited, and may be a regular shape or an irregular shape, preferably a regular shape, such as a square or a cylinder.
[0021] According to an embodiment of the present invention, the deposition platform can be a lifting deposition platform, preferably a deposition platform with a precisely controllable lifting height. The deposition platform is used to receive the cell ink extruded, stretched and solidified from the print head; preferably, the deposition platform is required to gradually descend as the number of printing layers increases; for example, the distance between the top of the print deposited on the deposition platform and the liquid surface where the electrolyte solution contacts the air is maintained between 0.5-2 mm, such as 0.8-1.5 mm, exemplified by 1 mm. Furthermore, the deposition platform is made of an inert biocompatible insulating material, such as glass or PP.
[0022] According to an embodiment of the present invention, the deposition platform comprises a sealing member to prevent the electrolyte solution from entering the dry area along the side pillars of the deposition platform.
[0023] According to an embodiment of the present invention, the deposition platform comprises a water-electric isolation component to prevent the dry area from leaking electricity and being transferred into the electrolyte solution.
[0024] According to an embodiment of the present invention, the electrolyte solution is a conductive solution, and the electrolyte solution can quickly gel the cell ink printed from the print head. For example, the electrolyte solution can be selected from a salt solution, such as at least one of a CaCl2 solution, a SrCl2 solution, and a MgCl2 solution, and an exemplary CaCl2 solution is used. Further, the electrolyte solution is connected to a ground wire.
[0025] According to an embodiment of the present invention, the 3D printing molding device also includes a 3D printing motion mechanism, which is connected to the extrusion-control module. Wherein, the 3D printing motion mechanism can be selected from known motion mechanisms in the art, for example, it can include a linear motion module, a rotational motion module, and a control mechanism connected to the linear motion module and the rotational motion module respectively, and the linear motion module and the rotational motion module are respectively connected to the extrusion-control module. Wherein, the linear motion module includes an X-axis linear motion mechanism, a Y-axis linear motion mechanism, and a Z-axis linear motion mechanism, which can realize the precise printing of the position of the nozzle in three-dimensional space. The rotational motion module is a 4th axis rotational motion device, which is directly connected to the printing nozzle and can realize the movement of the nozzle within a hemisphere. The control mechanism includes a servo motor controlled by a computer program. Limit sensors are set at both ends of the track of the X, Y, and Z axis linear motion mechanisms to ensure the safe operation of the motion mechanism. Under the control of the program, the servo motor drives the three linear motion mechanisms X, Y, and Z and a rotary motion mechanism to move precisely, which can complete 3D printing manufacturing in three-dimensional space; at the same time, due to the existence of the rotary motion mechanism, more complex parts can be printed.
[0026] According to an embodiment of the present invention, the 3D printing molding device also includes a 3D printing support platform, the 3D printing motion mechanism is arranged on the 3D printing support platform, and the insulating container is placed on the 3D printing support platform.
[0027] Furthermore, the present invention also provides a cell printing method using the solution bath near-field cell 3D printing device, which comprises the following steps: the cell ink squeezed out from the print head is drawn into filaments under the action of the electric field force; the filamentous cell ink is accurately printed onto a deposition platform, and the cell ink falling onto the deposition platform is rapidly gelled under the action of the electrolyte solution, completing the printing of one layer; then the deposition platform descends to start printing the next layer;
[0028] During the printing process of each layer, the distance between the top of the printed part and the liquid surface in contact with the electrolyte solution and the air must be maintained between 0.5-3 mm, such as 0.8-1.5 mm, and 1 mm is exemplary.
[0029] According to an embodiment of the present invention, the cell ink is extruded from the print head under the action of air pressure, and the air pressure is the driving force for the extrusion of the cell ink. For example, the air pressure is between 0.05-1MPa, such as 0.05-0.4MPa, 0.05-0.6MPa, 0.05-0.8MPa.
[0030] According to an embodiment of the present invention, the electric field force is generated by a near-field module, and the near-field module can be a high-voltage near-field module or a low-voltage near-field module, preferably a low-voltage near-field module. For example, the voltage of the low-voltage near-field module can be 0.1 to 10 kV, such as 0.5 to 8 kV, 1 to 7 kV, or 3 to 5 kV.
[0031] According to an embodiment of the present invention, due to the effect of the electric field force, the diameter of the cell ink filament can be 10 nm to 100 μm, such as 30 nm to 90 μm, 500 nm to 50 μm, or 1 to 10 μm.
[0032] According to an embodiment of the present invention, the print head has the meaning as described above. Further, the print head can be a multi-print head structure, which can realize the mixed printing of cell ink and scaffold material, and can also print the scaffold material separately from the cell ink and its culture medium. For example, the print head can be divided into two types, one print head prints cells and their culture matrix, and the other print head prints the scaffold. Further, the nozzle for printing cells can use multiple print heads to print different cells. In particular, a coaxial print head can also be used, and its inner channel and outer channel can print different cell inks.
[0033] According to an embodiment of the present invention, the 3D printing motion mechanism, the deposition platform and the electrolyte solution all have the meanings as described above.
[0034] According to an embodiment of the present invention, the cell printing method comprises the following steps:
[0035] (1) Generate air pressure through the extrusion-control module to extrude the cell ink from the print head;
[0036] (2) A potential difference is generated between the positive and negative electrodes of the low-voltage near-field module, thereby generating an electric field;
[0037] (3) Under the action of the electric field force, the extruded cell ink is drawn into a filament, and the cell ink is precisely printed onto the deposition platform under the control of the 3D printing motion mechanism. Under the action of the electrolyte solution, the cell ink falling on the deposition platform is quickly gelled to complete the printing of one layer; then the deposition platform descends and the printing of the next layer begins;
[0038] During the printing process of each layer, the distance between the top of the printed part and the liquid surface in contact with the electrolyte solution and the air must be maintained between 0.5-3 mm, such as 0.8-1.5 mm, and 1 mm is exemplary.
[0039] Beneficial effects of the present invention:
[0040] 1. The present invention greatly improves the fineness of cell 3D printing ink through the action of the electric field force of the near-field module. The printing method of the present invention can achieve a minimum fineness of 10nm for cell ink, thereby improving the accuracy of cell 3D printing, and the printing accuracy can reach 10μm. At the same time, the fineness of the device is adjustable, and the printing requirements of inks of different finenesses can be met.
[0041] 2. A solution bath collection module is provided in the 3D printing molding device of the present invention, so that the ink is gelled immediately at the moment of extrusion, which avoids the collapse caused by the low viscosity of the ink. At the same time, the low-viscosity cell ink can also have a higher cell density, higher cell viability, and better cell 3D printing performance.
[0042] 3. For the near-field module of the present invention, its positive electrode is a metal nozzle, and its negative electrode is in contact with the electrolyte liquid surface. As the printing progresses, the deposition platform continuously descends and the highest point of the printed part is always lower than the liquid surface of the electrolyte solution, so that the liquid surface is always kept horizontal, and the electrostatic field is therefore always uniform. This avoids the problem of electrostatic field disturbance caused by the increasing thickness of the printed part, and thicker printed parts can be printed.
[0043] 4. The present invention can realize simultaneous printing of multiple nozzles and can print different cell inks. At the same time, it can also realize the separate printing of cell ink and its matrix and scaffold material, which can save costs and make the printed product have more complex structure and function.
[0044] 5. Compared with traditional electrospinning, the present invention can accurately control the deposition site of the cell ink, thereby having the ability to print parts with complex geometric structures. BRIEF DESCRIPTION OF THE DRAWINGS
[0045] Figure 1 This is a schematic diagram of the structure of the near-field 3D printing molding device described in Example 1.
[0046] Figure 2 This is a schematic diagram of the structure of the gantry-type 3D printing motion mechanism in the 3D printing molding device described in Example 1.
[0047] Figure 3 This is a schematic diagram of the structure of the coaxial printing nozzle in the 3D printing molding device described in Example 1.
[0048] Figure numerals: 1-1 3D printing support platform 1-2 3D printing motion mechanism, 1-3 extrusion-control module, 1-4 cell ink receiving chamber, 1-5 low-voltage near-field module, 1-6 printing nozzle, 1-7 insulating container, 1-8 lifting deposition platform, 1-9 conductive electrolyte solution;
[0049] 2-1X axis linear motion mechanism, 2-2Y axis linear motion mechanism, 2-3Z axis linear motion mechanism, 2-4 4th axis rotation motion mechanism;
[0050] 3-1 coaxial print head. DETAILED DESCRIPTION
[0051] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of protection of the present invention. In addition, it should be understood that after reading the contents disclosed in the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope of protection defined by the present invention.
[0052] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, materials, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels.
[0053] Example 1
[0054] like Figure 1 The solution bath near-field cell 3D printing molding mechanism shown includes a 3D printing support platform 1-1, a 3D printing motion mechanism 1-2, an extrusion-control module 1-3, a cell ink receiving chamber 1-4, a low-pressure near-field module 1-5, a printing nozzle 1-6 and a solution bath collection module. The solution bath collection module includes an insulating container 1-7, a conductive electrolyte solution 1-9 placed in the insulating container 1-7, and a lifting deposition platform 1-8 immersed in the conductive electrolyte solution 1-9.
[0055] 3D printing motion mechanism 1-2 uses a gantry type 3D printing mechanism, such as Figure 2 As shown, it includes a linear motion module, a rotary motion module, and a control mechanism connected to the linear motion module and the rotary motion module respectively, and the linear motion module and the rotary motion module are connected to the extrusion-control module 1-3 respectively. The linear motion module mainly includes an X-axis linear motion mechanism 2-1, a Y-axis linear motion mechanism 2-2 and a Z-axis linear motion mechanism 2-3, which are used to realize the precise control of the position of the print nozzle 1-6 in three-dimensional space. The rotary motion module includes a fourth axis rotary motion mechanism 2-4, which is directly connected to the print nozzle 1-6, and is used to realize the movement of the print nozzle 1-6 in a hemispherical surface. The control mechanism mainly includes controlling the servo motor through a computer program, and setting limit sensors at both ends of the track of the X, Y, and Z axis linear motion mechanisms to ensure the safe operation of the motion mechanism. Under the control of the program, the servo motor drives the three linear motion mechanisms of X, Y, and Z and a rotary motion mechanism to move accurately, and 3D printing manufacturing in three-dimensional space can be completed. At the same time, due to the existence of the rotary motion mechanism, printing of more complex parts can be realized.
[0056] Extrusion-control module 1-3 is arranged above solution bath collection module, and it comprises pneumatic extrusion control module and print nozzle, and pneumatic extrusion control module comprises gas inlet and cell ink holding chamber 1-4, and the lower end of cell ink holding chamber 1-4 is connected to print nozzle 1-6. By adjusting the air pressure (air pressure range is 0.05-1MPa) passed into gas inlet, cell ink is extruded, and the rate of cell ink extrusion is controlled. The cell ink in cell ink holding chamber 1-4 has low viscosity and can make cells survive better. The material of pneumatic extrusion control module is biocompatible PP material.
[0057] Print head 1-6 is a medical stainless steel nozzle, which is connected to the positive electrode of low voltage near field module 1-5 (voltage range is 0.1-10kV). Print head 1-6 is a coaxial print head, and its structure is as follows Figure 3 As shown, the inner diameter is 0.15mm-1.5mm and the outer diameter is 0.3mm-2mm.
[0058] The low voltage near field module 1-5 is arranged on a side close to the print head 1-6, the voltage of the low voltage near field module 1-5 is 0.1-10 kV, and the negative electrode of the low voltage near field module 1-5 extends into the conductive electrolyte solution 1-9 in the insulating container 1-7.
[0059] The insulating container 1-7 is in the shape of a regular cylinder, and the lifting deposition platform 1-8 is used to receive the cell ink that is finally extruded, stretched and solidified. The lifting deposition platform 1-8 gradually descends as the number of printing layers increases, ensuring that the distance between the top of the print deposited on the lifting deposition platform 1-8 and the liquid surface of the conductive electrolyte solution 1-9 in contact with the air is maintained at 1mm. The deposition platform contains a sealing component and a water-electric isolation component. The sealing component can prevent the electrolyte solution from entering the dry area along the side column of the deposition platform, and the water-electric isolation component can prevent the dry area from leaking and entering the electrolyte solution. The conductive electrolyte solution 1-9 is connected to the ground wire. The insulating container 1-7 and the lifting deposition platform 1-8 are made of inert biocompatible insulating PP material. The conductive electrolyte solution 1-9 is a CaCl2 solution with good conductivity.
[0060] In the working state, the cell ink is extruded through the print head 1-6 under the action of air pressure, and is stretched and thinned by the electric field force under the action of the low-pressure near-field module 1-5, with the finest fineness reaching 10nm, and is deposited on the lifting deposition platform 1-8. The conductive electrolyte solution 1-9 has a gelling effect on the cell ink 1-4, and the printing ink 1-4 falling on the lifting deposition platform 1-8 will quickly form a gel. The print head 1-6 moves with the 3D printing motion mechanism 1-2 to complete the printing of a layer of pattern, and then the lifting deposition platform 1-8 descends to continue printing the next layer of pattern. During the printing process, the distance between the top of the print and the liquid surface of the conductive electrolyte solution 1-9 in contact with the air is always kept at 1mm.
[0061] The 3D printing motion mechanism 1-2 is arranged on the 3D printing support platform 1-1, and the insulating container 1-7 is placed on the 3D printing support platform 1-1.
[0062] Example 2
[0063] The difference from the first embodiment is that there are multiple print heads, and the multiple print heads are provided with a head temperature adjustment module for achieving adjustment at -10 to 260° C. to meet the printing requirements of different cells.
[0064] Example 3
[0065] Different from Example 1, the print head is a multi-nozzle structure, and the print heads are divided into two types: one nozzle is used to print cells and cell culture matrix, and can print multiple different cells; the other nozzle is used to print scaffolds. Similar to Example 1, the structure of the print head is a coaxial print head, and its inner channel and outer channel can print different cell inks.
[0066] Example 4 Solution bath near-field cell 3D printing molding method
[0067] This embodiment is a solution bath near-field cell 3D printing molding method, which is completed by the solution bath near-field cell 3D printing molding device provided in Example 3.
[0068] The solution bath near-field cell 3D printing molding method includes: generating air pressure through an extrusion-control module to extrude the cell ink from the printing nozzle; generating a potential difference between the positive and negative poles of the low-pressure near-field module, thereby generating an electric field; under the action of the electric field force, the extruded cell ink is drawn into filaments, and the cell ink is accurately printed onto a deposition platform under the control of a 3D printing motion mechanism; under the action of an electrolyte solution, the cell ink falling on the deposition platform is gelled at the moment of deposition; after completing the printing of one layer of pattern, the deposition platform descends and the printing of the next layer begins, and during the printing process, the distance between the top of the print and the liquid surface in contact with the electrolyte solution and the air is always maintained at 1 mm.
[0069] Among them, the power for extruding the cell ink is air pressure, which is 0.4Mpa. The electrostatic field is achieved by introducing a low-voltage near field, and the voltage of the low-voltage near field is 2.5kV. The cell ink is deposited under the action of the electrostatic field, and thinner filaments can be obtained compared to those deposited under gravity conditions. The diameter is controlled at 10nm~1μm, and the printing accuracy can reach 10μm. The cell ink uses sodium alginate as a template agent and 0.1M CaCl2 solution as an electrolyte solution.
[0070] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims
1. A solution bath near-field cell 3D printing device, characterized in that: The device includes a near-field module, an extrusion-control module, and a solution bath collection module; The extrusion-control module is arranged above the solution bath collection module; the extrusion-control module comprises a print head and a pneumatic extrusion control module, the print head is connected to the bottom end of the pneumatic extrusion control module; the pneumatic extrusion control module comprises a gas inlet and a cell ink receiving chamber; the cell ink is a low-viscosity cell ink containing at least one of sodium alginate, silk fibroin and collagen; The solution bath collection module includes an insulating container, an electrolyte solution contained in the insulating container, and a deposition platform immersed in the electrolyte solution; The distance between the printing nozzle of the extrusion-control module and the liquid surface where the electrolyte solution contacts the air is 0.5-40 mm; The near-field module is arranged between the extrusion-control module and the solution bath collection module, and the near-field module is connected to the extrusion-control module and the solution bath collection module respectively; the near-field module is arranged on a side close to the print nozzle, and the near-field module is a low-voltage near-field module; the near-field module is provided with a positive electrode and a negative electrode, the positive electrode is electrically connected to the print nozzle, and the negative electrode extends into the electrolyte solution in the insulating container; The deposition platform is a lifting deposition platform, and the deposition platform is used to receive the cell ink extruded, stretched and solidified from the printing nozzle; The deposition platform gradually descends as the number of printing layers increases. During the printing process of each layer, the distance between the top of the printed part deposited on the deposition platform and the liquid surface where the electrolyte solution contacts the air is controlled to be maintained at 0.5-3 mm; The deposition platform is made of an inert biocompatible insulating material; The electrolyte solution is selected from CaCl2 solution, SrCl2 solution and MgCl2 solution.
2. The solution bath near-field cell 3D printing device according to claim 1, characterized in that: The number of the printing nozzles is at least 1; When multiple print heads are set, coaxial print heads or non-coaxial print heads are selected; And / or, a temperature regulating module is provided on one or more print heads, and the temperature regulating module can be set to achieve regulation of -10 to 260°C; And / or, the diameter of the printing nozzle is 0.3mm-1mm; And / or, the printing nozzle is made of a biocompatible conductive metal material.
3. The solution bath near-field cell 3D printing device according to claim 2, characterized in that: The extrusion-control module is optionally provided with one or more coaxial printing nozzles, and the inner channel and the outer channel of the coaxial printing nozzle print different cell inks; And / or, the inner diameter of the coaxial printing nozzle is 0.15mm-1.5mm, and the outer diameter is 0.3mm-2mm.
4. The solution bath near-field cell 3D printing device according to claim 1, characterized in that: The material of the pneumatic extrusion control module is selected from biologically inert insulating materials.
5. The solution bath near-field cell 3D printing device according to claim 1, characterized in that: The insulating container has a regular shape or an irregular shape.
6. The solution bath near-field cell 3D printing device according to claim 1, characterized in that: The electrolyte solution is connected to a ground wire.
7. The solution bath near-field cell 3D printing device according to claim 1, characterized in that: The 3D printing molding device also includes a 3D printing motion mechanism, which is connected to the extrusion-control module.
8. The solution bath near-field cell 3D printing device according to claim 7, characterized in that: The 3D printing motion mechanism includes a linear motion module, a rotary motion module, and a control mechanism connected to the linear motion module and the rotary motion module respectively, and the linear motion module and the rotary motion module are respectively connected to the extrusion-control module; the linear motion module includes an X-axis linear motion mechanism, a Y-axis linear motion mechanism and a Z-axis linear motion mechanism, the rotary motion module is a fourth-axis rotary motion device, which is directly connected to the printing nozzle, and the control mechanism includes a servo motor controlled by a computer program.
9. The solution bath near-field cell 3D printing device according to claim 7, characterized in that: The 3D printing molding device also includes a 3D printing support platform, the 3D printing motion mechanism is arranged on the 3D printing support platform, and the insulating container is placed on the 3D printing support platform.
10. A cell printing method using the solution bath near-field cell 3D printing device according to any one of claims 1 to 9, comprising the following steps: the cell ink squeezed out from the print head is drawn into filaments under the action of an electric field force; the filamentous cell ink is accurately printed onto a deposition platform, and the cell ink falling onto the deposition platform is rapidly gelled under the action of an electrolyte solution, completing the printing of a layer; then the deposition platform descends to start printing the next layer; During the printing process of each layer, the distance between the top of the printed part and the liquid surface where the electrolyte solution and air are in contact must be maintained between 0.5-3mm.
11. The method according to claim 10, characterized in that The cell ink is squeezed out from the print head under the action of air pressure; And / or, the electric field force is generated by a near-field module; And / or, the diameter of the cell ink filament is 10 nm to 100 μm.
12. The method according to claim 11, characterized in that The air pressure is between 0.05-1 MPa; and / or the voltage of the near-field module is between 0.1 and 10 kV.
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