Printing nozzle, biological 3D printer and printing control method

Abstract

Disclosed in the present invention are a printing nozzle, a biological 3D printer and a printing control method. The printing nozzle of the present invention comprises a main body, a nozzle and a drive module, a plurality of bio-ink cavities being defined in the main body. The nozzle comprises a discharge section and a plurality of branch sections, each branch section being connected to the discharge section. A first channel is defined inside each branch section, and a second channel is defined inside the discharge section, one end of each first channel being communicated with a corresponding bio-ink cavity, and the other end of each first channel being communicated with the second channel. The drive module is connected to the main body, and is used for driving each bio-ink cavity to supply a bio-ink to the nozzle. The present printing nozzle can achieve the extrusion of various bio-inks and can realize precise and orderly spatial arrangement of various cells or biological materials by means of voxelization programming, thereby facilitating construction of complex tissue or organs.

Description

Printing nozzle, biological 3D printer and printing control method TECHNICAL FIELD

[0001] The present application relates to the technical field of 3D printing, in particular to a printing nozzle, a biological 3D printer and a printing control method. BACKGROUND

[0002] Biological 3D printing is a rapid prototyping technology based on the principle of "discrete accumulation" to build three-dimensional functional class organization / organ in a layer-by-layer manner. In the printing process, the solution containing cells or factors is controlled by a computer, and is extruded in the form of droplets or microfilaments through a nozzle, and is quickly cross-linked and solidified on the surface of the substrate, and through layer-by-layer stacking, it is expected to achieve the purpose of accurately constructing three-dimensional complex tissue and organ structure.

[0003] In the prior art, the single nozzle of the biological 3D printer is only provided with a biological ink channel, and only one kind of cells and materials can be printed at a time, and the fine structure printing of multiple cells and materials cannot be achieved.

[0004] SUMMARY

[0005] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application provides a printing nozzle capable of extruding multiple biological inks and achieving precise and orderly arrangement of multiple cells or biological materials in space through voxel programming, so as to construct complex tissues or organs.

[0006] The present application also provides a biological 3D printer having the above printing nozzle.

[0007] The present application also provides a printing control method having the above biological 3D printer.

[0008] The printing nozzle according to the first aspect of the present application comprises:

[0009] a main body, the main body defining a plurality of biological ink cavities;

[0010] a nozzle comprising a discharge section and a plurality of branch sections, each of the branch sections being connected with the discharge section, the inside of each of the branch sections defining a first channel, the inside of the discharge section defining a second channel, one end of each of the first channels being in communication with a corresponding one of the biological ink cavities, and the other end being in communication with the second channel;

[0011] a driving module connected with the main body and configured to drive the biological ink cavities to supply biological ink to the nozzle.

[0012] The printing nozzle according to the present application has at least the following beneficial effects:

[0013] In the embodiment of the present application, the printing nozzle can realize the extrusion of multiple biological inks through the same nozzle. Compared with the prior art 3D printer which can only print a single biological ink, the printing nozzle of the present application can realize the extrusion of multiple biological inks, so as to realize the precise and orderly arrangement of multiple cells or biological materials in space through voxel programming, so as to construct a complex tissue or organ. Compared with the disc-type multi-nozzle 3D printer, the integrated single nozzle of the present application does not need to rotate the disc when switching the printing material, and only needs to switch the supply relationship of each biological ink to realize the switching of the printing material, so the switching speed is faster. The printing nozzle of the present application can switch the discharging frequency of different biological ink cavities to 1 Hz to 50 Hz, which has a higher printing speed. Since it is not limited by the size of the disc, the nozzle of the present application can be connected to a larger number of branch sections, so as to correspond to a larger number of biological ink cavities, and has more material storage capacity and material selection capacity compared with the disc-type 3D printer. Moreover, the position of the nozzle does not change when the material is switched, and the switching of the material does not affect the position accuracy of the nozzle, effectively avoiding the movement of the nozzle position before and after the material switching, thereby improving the printing accuracy of the 3D printer. In addition, since each printing material needs to be extruded through the second channel when extruded, before and after the printing material is switched, different biological inks still have good continuity, which ensures the forming effect of the printing nozzle.

[0014] According to some embodiments of the present application, the driving module comprises a plurality of electromagnetic valves and a plurality of air inlet pipes, one end of each air inlet pipe is connected to an external pressure source, and the other end is connected to the biological ink cavity, the electromagnetic valve is connected to the air inlet pipe and used to control the opening and closing of the air inlet pipe;

[0015] In response to the air inlet pipe being connected, the corresponding biological ink cavity supplies biological ink to the nozzle, and in response to the air inlet pipe being cut off, the corresponding biological ink cavity stops supplying biological ink to the nozzle.

[0016] According to some embodiments of the present application, when any of the air inlet pipes is connected, the remaining air inlet pipes are cut off by the electromagnetic valve.

[0017] According to some embodiments of the present application, the connection position of each branch section to the discharge port of the discharge section is equal, and each branch section is distributed along the circumference of the discharge section.

[0018] Alternatively, the distance from the connection position of each branch section to the discharge port of the discharge section is not equal, and each branch section is sequentially connected to the discharge section along the length direction of the discharge section.

[0019] According to some embodiments of the present application, the printing nozzle switches the discharging frequency of different biological ink cavities at 1 Hz to 50 Hz.

[0020] According to some embodiments of the present application, the printing nozzle further comprises a temperature control module connected with the main body, for controlling the temperature in the biological ink cavity at 0℃ to 40℃.

[0021] The biological 3D printer according to the second aspect of the embodiments of the present application comprises:

[0022] A rack provided with a movement module;

[0023] A printing nozzle connected with the movement module and moving with the movement of the movement module, as described in any of the above embodiments;

[0024] A controller in communication connection with the movement module and the printing nozzle respectively, for regulating the position and printing parameters of the printing nozzle

[0025] The biological 3D printer according to the embodiments of the present application has at least the following beneficial effects:

[0026] In the printing process, the cell or factor solution is extruded in the form of droplets or microfilaments through the nozzle under the control of the computer, rapidly cross-linked and solidified on the substrate surface, and stacked layer by layer to achieve the purpose of precisely constructing a three-dimensional complex tissue and organ structure. Based on the integrated printing nozzle and with the aid of the programmable highly controllable air pressure control process, continuous extrusion of multiple materials can be realized, and cell / material controllable change hydrogel filament units can be constructed. Further, through the movement and positioning of the nozzle, stable accumulation of hydrogel filaments can be realized, voxel-level stacking of cell arrangement from point units to line units to surface units is achieved, and the model printing resolution is improved.

[0027] According to some embodiments of the present application, the driving module is configured to drive each biological ink cavity to supply biological ink to the nozzle in a set order in response to the instruction of the controller, so that the nozzle sprays different biological inks in a set order.

[0028] And / or, the movement module is configured to drive the printing nozzle to move along a set path in response to the instruction of the controller, so that the nozzle sprays the biological ink along the set path.

[0029] The printing control method according to the third aspect of the embodiments of the present application comprises the following steps:

[0030] Constructing a three-dimensional model of the object to be printed;

[0031] The three-dimensional model is divided into functional structures, and different biological ink cavities are filled with corresponding biological ink corresponding to different functional structures, and each functional structure is matched with at least one biological ink.

[0032] The printing nozzle is controlled to print the to-be-printed object, and when printing any functional structure, the biological ink cavity corresponding to the functional structure is driven to supply biological ink to the nozzle.

[0033] According to some embodiments of the present application, the functional structures include at least hard tissue components and soft tissue components, and the main body defines at least a first biological ink cavity filled with a first viscosity material and a second biological ink cavity filled with a second viscosity material, wherein the viscosity of the first viscosity material is less than the viscosity of the second viscosity material.

[0034] When the printing nozzle is ready to print the soft tissue component, the first biological ink cavity is driven to supply the first viscosity material to the nozzle; and when the printing nozzle is ready to print the hard tissue component, the second biological ink cavity is driven to supply the second viscosity material to the nozzle.

[0035] Additional aspects and advantages of the present application will be given in part in the following description, some of which will become apparent from the following description, or will be learned by practice of the present application. BRIEF DESCRIPTION OF DRAWINGS

[0036] The present application will be further described below in conjunction with the accompanying drawings and embodiments, wherein:

[0037] Fig. 1 is a structural schematic diagram of a printing nozzle according to an embodiment of the present application;

[0038] Fig. 2 is a structural schematic diagram of the printing nozzle according to an embodiment of the present application from another angle;

[0039] Fig. 3 is a structural schematic diagram of the printing nozzle according to an embodiment of the present application with part of the main body and the temperature control module hidden;

[0040] Fig. 4 is a connection schematic diagram of a biological ink tube and a nozzle according to an embodiment of the present application;

[0041] Fig. 5 is a structural schematic diagram of a nozzle according to an embodiment of the present application;

[0042] Fig. 6 is an electrical control schematic diagram of a biological 3D printer according to an embodiment of the present application;

[0043] Fig. 7 is a schematic diagram of a sample printed by a biological 3D printer according to an embodiment of the present application;

[0044] Fig. 8 is a schematic diagram of a lung alveolus organ printed by a biological 3D printer according to an embodiment of the present application;

[0045] Fig. 9 is a schematic diagram of a biological 3D printer printing glomerulus organ according to an embodiment of the present application;

[0046] Fig. 10 is a schematic diagram of a biological 3D printer printing bone organ according to an embodiment of the present application.

[0047] Reference signs:

[0048] Body 100; biological ink pipe 110;

[0049] Nozzle 200; discharge section 210; branch section 220;

[0050] Drive module 300; electromagnetic valve 310;

[0051] Temperature control module 400; finned heat sink 410; exhaust fan 420;

[0052] To be printed 500;

[0053] Controller 600. DETAILED DESCRIPTION

[0054] The embodiments of the present application are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference signs represent the same or similar elements or elements having the same or similar functions throughout. The embodiments described below by referring to the accompanying drawings are exemplary and are only used to explain the present application, and cannot be understood as a limitation of the present application.

[0055] In the description of the present application, it should be understood that the orientation description, such as the orientation or position relationship indicated by up, down, front, back, left, right, etc. is based on the orientation or position relationship shown in the drawings, and is only for the convenience of describing the present application and simplifying the description, and does not indicate or imply that the device or element indicated must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation of the present application.

[0056] In the description of the present application, if the meaning of several is more than one, the meaning of multiple is more than two, greater than, less than, more than, etc. is not included in the number, and above, below, etc. is included in the number. If it is described as first, second, it is only used for the purpose of distinguishing technical features, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features or the order of indicated technical features.

[0057] In the description of the present application, unless otherwise explicitly limited, the words such as setting, installing, connecting, etc. should be broadly understood, and the person skilled in the art can reasonably determine the specific meaning of the above words in the present application in combination with the specific content of the technical solution.

[0058] In the description of the application, the description of the terms "one embodiment", "some embodiments", "illustrative embodiment", "example", "specific example", or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the application. In the description, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in one or more embodiments or examples.

[0059] Biological 3D printing is a rapid prototyping technology based on the principle of "discrete-piling" to construct three-dimensional functional class tissues / organs in a layer-by-layer manner. In the printing process, the solution containing cells or factors is controlled by a computer, and is extruded in the form of droplets or microfilaments through a nozzle, and is quickly cross-linked and solidified on the surface of the substrate. Through layer-by-layer stacking, it is expected to achieve the purpose of accurately constructing three-dimensional complex tissue and organ structures.

[0060] Compared with traditional tissue construction methods, biological 3D printing not only has unique technical advantages in constructing large-size centimeter-level class tissues / organs, but also can simultaneously locate living cells and extracellular matrix in the specified layer-by-layer stacked tissue, accurately control the spatial distribution of living cells, proteins, DNA, drugs, growth factors and other bioactive substances, and control the formation of biological tissues. At the same time, the biological 3D printing method has the advantages of precision, repeatability and strong size controllability in constructing class organs. However, the existing biological 3D printing technology can only control the initial relative position of a single type of living cells and biological materials, while the real tissue and organ development is the result of the ordered action of multiple cells and multiple growth factors and other factors in time and space.

[0061] Specifically, in the prior art, the single nozzle of the biological 3D printer is equipped with only one biological ink channel, and only one type of cells and materials can be printed at a time, which cannot realize the fine structure printing of multiple cells and materials, and cannot construct a class tissue or organ model with high structural and functional simulation.

[0062] To solve the above problems, the application provides a printing nozzle, as shown in FIGS. 1-3, which comprises a main body 100, a nozzle 200 and a driving module 300, wherein the main body 100 is a frame of the printing nozzle, used for mounting the nozzle 200, the driving module 300 and a temperature control module 400, etc., and the main body 100 is defined with a plurality of bio-ink cavities for storing bio-ink. In the embodiment shown in FIG. 3, the main body 100 is defined with a receiving cavity, in which a bio-ink tube 110 is arranged, and the bio-ink tube 110 is defined with a bio-ink cavity for storing bio-ink. Bio-ink is a material containing bioactive components specially used for 3D bio-printing. It can realize in-vitro construction of cells, tissues and organs, and can be divided into two categories: cell-based bio-ink and non-cell-based bio-ink. The cell-based bio-ink mainly contains living cells, which is used for constructing complex tissues or organs with physiological functions; and the non-cell-based bio-ink mainly contains bioactive molecules, which is used for regulating cell behavior or providing bioactive support.

[0063] The nozzle 200 is in communication with the bio-ink cavities, used for outputting bio-ink and stacking bio-materials, cells and growth factors, etc. according to a preset three-dimensional model, so as to construct tissues and organs with specific morphology, structure and function. The bio-ink filled in each bio-ink cavity can be inconsistent, for example, the cell-based bio-ink is filled in one bio-ink cavity, and the non-cell-based bio-ink is filled in another bio-ink cavity, so that the nozzle 200 can call different bio-ink for printing.

[0064] Specifically, as shown in FIGS. 4 and 5, the nozzle 200 of the application comprises a discharging section 210 and a plurality of branch sections 220, the discharging section 210 is defined with a discharging port, and each branch section 220 is defined with an inlet port. Each branch section 220 is connected with the discharging section 210. The inside of each branch section 220 is defined with a first channel, and the inside of the discharging section 210 is defined with a second channel, one end of each first channel (i.e. the end defined with the inlet port) is in communication with the corresponding bio-ink cavity, and the other end is in communication with the second channel, so that the bio-ink can be extruded from the discharging port of the discharging section 210 through the first channel and the second channel.

[0065] The nozzle 200 can be formed by 3D printing with metal or resin material, or by mold processing.

[0066] It can be understood that the bio-ink has a certain viscosity, and the pipe diameters of the first channel and the second channel in the nozzle 200 are small, and the first pipe and the second pipe are capillary pipes, and the size of the discharge port is in the range of 50 μm to 500 μm. Without the action of external driving force, the bio-ink is affected by surface tension and is stagnant in the bio-ink cavity. Therefore, the printing nozzle of the embodiment of the present application further has a driving module 300 connected with the main body 100, which acts on the bio-ink cavity to drive any one of the bio-ink cavities to supply bio-ink to the nozzle 200.

[0067] In some more specific embodiments, the driving module 300 can drive the bio-ink to flow to the nozzle 200 by adjusting the size of the air pressure in the bio-ink cavity, for example, as shown in FIGS. 3 and 4, the driving module 300 includes a plurality of electromagnetic valves 310 and a plurality of air inlet pipes, one end of each air inlet pipe is connected with an external pressure source, and the external pressure source is a high pressure source. The other end of each air inlet pipe is connected with the bio-ink cavity, and the electromagnetic valve 310 is connected with the air inlet pipe for controlling the opening and closing of the air inlet pipe. When the electromagnetic valve 310 is opened and the air inlet pipe is connected, the bio-ink cavity is connected with the high pressure source, and under the action of high pressure, the bio-ink in the bio-ink cavity flows towards the nozzle 200 and is extruded from the nozzle 200; when the electromagnetic valve 310 is closed and the air inlet pipe is blocked by the electromagnetic valve 310, the bio-ink cavity restores to normal pressure, and the bio-ink cavity stops supplying bio-ink to the nozzle 200.

[0068] By controlling the pressure size of the high pressure source or by controlling the opening degree of the electromagnetic valve 310, the extrusion speed of the bio-ink can be adjusted, and the greater the pressure difference between the high pressure source and the bio-ink cavity or the greater the opening degree of the electromagnetic valve 310, the faster the extrusion speed of the bio-ink. By controlling the opening time of the electromagnetic valve 310, the extrusion volume of the bio-ink can be adjusted, and the longer the opening time, the greater the extrusion volume of a single bio-ink.

[0069] It can be understood that the gas injection method mentioned in the above embodiment adjusts the extrusion of the bio-ink at the nozzle 200 by controlling the inlet of high pressure gas through the electromagnetic valve 310. The advantage of this method is that the action of gas flow on the biological material will not produce hysteresis effect, and the material will not produce flow saliva and other adverse printing conditions at the discharge port. In the printing process, the high pressure source such as a digital pressure regulator, an air pump, etc. provides pressure to the bio-ink cavity filled with bio-ink, and the electromagnetic valve 310 controls the opening and closing of the gas path. The electromagnetic valve 310 is operated by a digital relay from 0 to 24V, and in order to ensure the stability of the printing process, each bio-ink cavity has an independent air pressure control path.

[0070] Further, when any air inlet pipe is connected, the remaining air inlet pipes are blocked by the electromagnetic valve 310, so that the nozzle 200 extrudes a single bio-ink.

[0071] In some embodiments, the driving module 300 can also be a gas pump, a hydraulic pump or the like device, so as to squeeze the bio-ink in the bio-ink cavity to adjust the hydraulic pressure to drive the bio-ink to flow to the nozzle 200. For example, the driving module 300 comprises a plurality of gas pressure pumps (not shown in the figure), each of which corresponds to a bio-ink cavity. The output shaft of the gas pressure pump can be extended or retracted relative to the pump body, one end of the output shaft is connected with the pump body, and the other end is inserted into the bio-ink cavity and is in sealing connection with the cavity wall of the bio-ink cavity. When the output shaft is extended to squeeze the liquid in the bio-ink cavity, the bio-ink escapes from the first pipeline and is extruded from the nozzle 200. Similarly, by controlling the extrusion speed of the gas pressure pump, the extrusion speed of the bio-ink can be controlled, and the greater the extrusion speed of the gas pressure pump, the faster the extrusion speed of the bio-ink. By controlling the output shaft to extend at a constant speed, the bio-ink can be extruded at a constant speed.

[0072] The driving module 300 can also be in other forms of settings, such as pumping bio-ink into the bio-ink cavity to increase the hydraulic pressure, and the like, which will not be described in detail herein.

[0073] It should be noted that in some embodiments, the driving module 300 only drives the bio-ink in a single bio-ink cavity to supply the nozzle 200 at the same time, and the bio-ink in the remaining bio-ink cavities remains unchanged. In some other embodiments, the driving module 300 can also drive the bio-ink in multiple bio-ink cavities to supply the nozzle 200 at the same time, so as to realize the mixed extrusion of multiple biological materials.

[0074] Based on the above, in the embodiments of the present application, the printing nozzle can realize the extrusion of multiple bio-inks through the same nozzle 200. Compared with the 3D printer in the prior art which can only print a single bio-ink, the printing nozzle of the present application can realize the extrusion of multiple bio-inks, so as to realize the precise and orderly arrangement of multiple cells or biological materials in space through voxel programming, so as to construct a complex tissue or organ.

[0075] Compared with the 3D printer of the wheel disc type multi-nozzle 200, the integrated single nozzle 200 of the present application does not need to rotate the wheel disc when switching the printing material, and only needs to switch the supply relationship of each bio-ink to realize the switching of the printing material, and the switching speed is faster. The discharge frequency of the printing head of the present application for switching different bio-ink cavities can reach 1Hz to 50Hz, which has a higher printing speed. Since it is not limited by the size of the wheel disc, the nozzle 200 of the present application can be connected to a larger number of branch sections 220, so as to correspond to a larger number of bio-ink cavities, and has more material storage capacity and material selection capacity compared with the wheel disc type 3D printer. Moreover, the position of the nozzle 200 does not change when the material is switched, and the switching of the material does not affect the position accuracy of the nozzle 200, effectively avoiding the movement of the nozzle 200 position before and after the material switching, thereby improving the printing accuracy of the 3D printer. In addition, since each printing material needs to be extruded through the second channel, the different bio-inks still have good continuity before and after the printing material is switched, which ensures the forming effect of the printing head.

[0076] In some embodiments, as shown in FIG. 5, the connection position of each branch section 220 to the discharge port of the discharge section 210 is equal to the distance of the discharge port of the discharge section 210, that is, each branch section 220 is connected to the same length position of the discharge section 210, and each branch section 220 is distributed along the circumference of the discharge section 210, thereby forming an umbrella structure. Alternatively, as shown in FIG. 6, each branch section 220 is connected to the same length position of the discharge section 210 and is arranged at different angles with the discharge section 210. It can be understood that the discharge section 210 of such a nozzle 200 can be arranged to be shorter, thereby shortening the distance of the bio-ink from the bio-ink cavity to the discharge port, and further reducing the damage of the temperature, pressure, etc. to the biological material in the process.

[0077] In other embodiments (not shown in the figure), the distance from the connection position of each branch section 220 to the discharge port of the discharge section 210 is not equal to the distance of the discharge port of the discharge section 210, that is, along the length direction of the discharge section 210, each branch section 220 is connected to the discharge section 210 in turn, thereby forming a tree structure. It can be understood that the length of the discharge section 210 of such a nozzle 200 can be determined according to the number of branch sections 220, which can accommodate more branch sections 220, and is suitable for printing scenarios where more types of bio-ink are required.

[0078] In some embodiments, because the bio-ink usually contains bioactive components such as cells, proteins, DNA or other biological molecules, these components are very sensitive to temperature changes. Therefore, the printing head further comprises a temperature control module 400 connected with the main body 100, which is used to control the temperature in the bio-ink cavity at 0℃ to 40℃, so as to maintain the activity of the bioactive components in the bio-ink.

[0079] Specifically, each bio-ink tube 110 can be arranged in parallel as shown in FIG. 6, or arranged in an array as shown in FIG. 3. The temperature control module 400 can include a temperature sensor arranged on the cavity wall of the accommodating cavity of the main body 100, for detecting the temperature in the accommodating cavity, so as to feedback to the temperature control module 400 for temperature adjustment. The temperature control module 400 can further include a heat dissipation member, such as the embodiment shown in FIGS. 2 and 3, which includes a finned heat sink 410, the main body of which is attached to the outer wall of the main body 100, thereby absorbing heat and conducting it to the fins, which have a large contact area with air, thereby being able to dissipate to the surrounding environment through air convection, to achieve cooling. To speed up the heat dissipation speed of the finned heat sink 410, the heat dissipation member further includes an exhaust fan 420 to increase the heat exchange speed between the finned heat sink 410 and the air.

[0080] In addition, it can be understood that the temperature control module 400 can further include a heating member (not shown), which is connected to the main body 100 and can provide heat to the accommodating cavity to avoid the temperature in the accommodating cavity being too low to cause the bio-ink to be inactivated. Through the synergistic effect of the heat dissipation member and the heating member, the temperature in the accommodating cavity can be kept relatively constant, thereby improving the survival rate of cell printing.

[0081] In other embodiments, the temperature control module 400 can also be a water bath device, in which each bio-ink tube 110 is stored in a water tank, and the temperature of the water is adjusted to maintain the temperature of the bio-ink within a suitable range and relatively stable. It can be understood that, due to the large specific heat capacity of water, the temperature change is small, which can have a good constant temperature effect.

[0082] The second aspect embodiment of the present application proposes a biological 3D printer, which includes a rack, a controller 600, and a printing nozzle mentioned in any of the above embodiments. The rack is provided with a motion module, which can be an XYZ three-axis moving mechanism, or a mechanical arm, a mechanical hand, etc. with more degrees of freedom. The printing nozzle is connected to the motion module and moves with the motion module, so as to print a three-dimensional structure layer by layer on a substrate. The controller 600 is in communication connection with the motion module and the printing nozzle, to control the position and printing parameters of the printing nozzle, including but not limited to: the type of extruded bio-ink, the extrusion speed, the extrusion volume, etc.

[0083] It can be understood that, by using an integrated printing nozzle, the biological 3D printer can realize voxel-level printing of relatively complex tissues or organs, and has a faster printing speed and better printing effect.

[0084] Specifically, during the printing process, the driving module 300 drives each bio-ink chamber to supply bio-ink to the nozzle 200 according to a set order in response to the instruction of the controller 600, so that the nozzle 200 sprays different bio-ink according to the set order. Moreover, the motion module coupled with the driving module 300 also drives the printing nozzle to move along a set path in response to the instruction of the controller 600, so that the nozzle 200 sprays bio-ink along the set path.

[0085] In the embodiment shown in FIG. 3, the driving module 300 is a pneumatic module controlled by the electromagnetic valve 310. During the printing process, the cell or factor solution contained therein is extruded through the nozzle 200 in the form of droplets or microfilaments under the control of a computer, rapidly cross-linked and solidified on the surface of a substrate, and stacked layer by layer to achieve the purpose of precisely constructing a three-dimensional complex tissue or organ structure. Based on the integrated printing nozzle and with the aid of a programmable highly controllable pneumatic control process, continuous extrusion of multiple materials can be achieved, and a hydrogel filament unit with controllable changes in cells / materials can be constructed. Further, through the movement and positioning of the printing nozzle, stable accumulation of the hydrogel filament can be achieved, voxel-level stacking of cell arrangement from a point unit to a line unit and then to a surface unit is realized, and the model printing resolution is improved.

[0086] Through coupling with a multi-channel electromagnetic valve, debugging printing is performed, and a sample as shown in FIG. 7 is formed. In the sample, each layer of cell structure contains multiple cells, and multiple layers of cell structure are sequentially stacked to form a three-dimensional complex cell tissue, which demonstrates the feasibility of the biological 3D printer of the present application.

[0087] The biological 3D printer of the present application can also be applied to the field of organ manufacturing. As shown in FIG. 8, the biological 3D printer of the present application is applied to design and print an alveolar organ, simulate an alveolar structure, and orderly distribute multiple different cell types at different positions in space through the multi-channel structure of the nozzle 200. The bio-ink chambers of the printing nozzle respectively include flat epithelial cells, secretory epithelial cells, septal cells, and vascular endothelial cells. The biological 3D printer can perform voxelized fine printing imaging to construct an alveolar organ.

[0088] In the embodiment shown in FIG. 9, the biological 3D printer of the present application is applied to design and print a glomerular organ, simulate a glomerular structure, and orderly distribute multiple different cell types at different positions in space through the multi-channel structure of the nozzle 200. The bio-ink chambers of the printing nozzle respectively include epithelial cells, glomerular basement membrane, and podocytes. The biological 3D printer can perform voxelized fine printing imaging to construct a glomerular organ.

[0089] In the embodiment shown in FIG. 10, the biological 3D printer of the present application is applied to design and print bone-like organs, simulate bone tissue structure, and orderly distribute different cell types at different positions in space through the multi-channel nozzle 200. The biological ink cavities of the printing nozzle respectively include mesenchymal stem cells, monocytes, vascular endothelial cells, nerve cells, etc. The biological 3D printer can perform voxelized fine printing imaging to construct bone-like organs.

[0090] The third aspect embodiment of the present application also proposes a printing control method applied to the biological 3D printer of the second aspect embodiment, which includes the following steps:

[0091] S100, constructing a three-dimensional model of a to-be-printed object;

[0092] When constructing the three-dimensional model of the to-be-printed object 500, the specific requirements and specifications of the printing target need to be determined first, including its shape, size, function, and expected biological compatibility, etc. Then, professional biological modeling software is used to perform fine three-dimensional modeling according to these requirements. Alternatively, in some other embodiments, a three-dimensional model can also be constructed by a scanning mechanism, etc.

[0093] S200, dividing the three-dimensional model into functional structures, and filling corresponding biological ink into different biological ink cavities corresponding to different functional structures, each of the functional structures being matched with at least one of the biological inks;

[0094] After obtaining the three-dimensional model, different functional structures (such as bones, muscles, blood vessels, etc.) in the model need to be divided. Each functional structure corresponds to one or more specific biological inks, which may include different cell types, growth factors, biological materials, etc. Then, these biological inks are filled into the corresponding biological ink cavities for on-demand supply during the printing process. The accurate division of functional structures and the reasonable matching of biological inks are the key to realizing the printing of complex biological bodies. Correct biological ink can promote cell growth and differentiation, simulate the natural process in the biological body, and thus endow the printed product with higher biological activity and functionality.

[0095] Then, the three-dimensional model is processed by layering with the help of printing software, and the path planning of the printing nozzle is performed to form digital printing instructions.

[0096] S300, controlling the printing nozzle to print the to-be-printed object, and driving the corresponding biological ink cavity to supply biological ink to the nozzle when printing any functional structure.

[0097] According to the printing instructions, the printing nozzle and the movement module execute the printing action. During the printing process, the printing nozzle needs to move accurately according to the preset printing path and parameters. These parameters include the moving speed of the nozzle 200, the extrusion pressure, the extrusion time, and the distance between the nozzle 200 and the substrate, etc. At the same time, the printing control system needs to monitor the state of each bio-ink cavity in real time to ensure that they can supply bio-ink to the nozzle 200 in time and accurately when needed. When printing any functional structure, the control system will trigger the driving module 300 of the corresponding bio-ink cavity to make the bio-ink be sprayed onto the printing platform at a stable speed and flow. With the movement of the printing nozzle and the layer-by-layer accumulation of the bio-ink, the biological body with complex structure and multiple functions is finally formed.

[0098] In the above step S200, further, the functional structure at least includes hard tissue components and soft tissue components, the soft tissue components include muscles, blood vessels, organs, etc., and the hard tissue components include bones, etc. At least one bio-ink cavity is filled with a first viscosity material, which is named as a first bio-ink cavity for convenience, and at least another bio-ink cavity is filled with a second viscosity material, which is named as a second bio-ink cavity for convenience. It should be noted that the viscosity of the first viscosity material is less than that of the second viscosity material. The first viscosity material can be a hydrogel material with shear thinning and rapid crosslinking characteristics, or a low-viscosity material that can provide a suitable microenvironment for maintaining cell viability and functionality. The second viscosity material can be a high-viscosity material that can provide mechanical support for the printed structure. By matching different bio-inks with different functional structures, the adaptability of the printing material and the to-be-printed object 500 can be improved, so as to construct more structure and function emulating biotissues and organ models.

[0099] The embodiments of the present application are described in detail above in combination with the drawings, but the present application is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the purpose of the present application. In addition, the embodiments of the present application and the features in the embodiments can be combined with each other without conflict.

Claims

1. A print head, characterized by, The printing nozzle comprises: a main body, the main body defining a plurality of bio-ink cavities; a nozzle comprising a discharge section and a plurality of branch sections, each of the branch sections being connected with the discharge section, the inside of each of the branch sections defining a first channel, the inside of the discharge section defining a second channel, one end of each of the first channels being in communication with a corresponding bio-ink cavity, the other end of each of the first channels being in communication with the second channel; a driving module connected with the main body, for driving each of the bio-ink cavities to supply bio-ink to the nozzle.

2. The print head of claim 1, wherein, The driving module comprises a plurality of electromagnetic valves and a plurality of air inlet pipes, one end of each of the air inlet pipes being in communication with an external pressure source, the other end of each of the air inlet pipes being in communication with a bio-ink cavity, the electromagnetic valves being connected with the air inlet pipes, for controlling the opening and closing of the air inlet pipes; wherein, in response to the air inlet pipe being in communication, the corresponding bio-ink cavity supplies bio-ink to the nozzle, and in response to the air inlet pipe being blocked, the corresponding bio-ink cavity stops supplying bio-ink to the nozzle.

3. The printing head of claim 2, wherein, When any of the air inlet pipes is in communication, the rest of the air inlet pipes are blocked by the electromagnetic valves.

4. The printing die of claim 1, wherein, The connection position of each of the branch sections to the discharge section is equal to the distance from the connection position to the discharge port of the discharge section. Alternatively, the connection position of each of the branch sections to the discharge section is not equal to the distance from the connection position to the discharge port of the discharge section, and each of the branch sections is sequentially connected with the discharge section along the length direction of the discharge section.

5. The printing die of claim 1, wherein, The printing nozzle switches the discharge frequency of different bio-ink cavities at 1 Hz to 50 Hz.

6. The printing die of claim 1, wherein, The printing nozzle further comprises a temperature control module connected with the main body, for controlling the temperature of the bio-ink cavities at 0°C to 40°C.

7. A biological 3D printer characterized by, The printing nozzle comprises: a rack provided with a movement module; the printing nozzle of any one of claims 1 to 6, the printing nozzle being connected with the movement module and moving with the movement of the movement module; a controller in communication connection with the movement module and the printing nozzle, for regulating the position and printing parameters of the printing nozzle.

8. The biological 3D printer according to claim 7, characterized in that, The driving module is configured to drive each of the bio-ink cavities to supply bio-ink to the nozzle in a set order in response to the instruction of the controller, so that the nozzle sprays different bio-ink in a set order; and / or, the movement module is configured to drive the printing nozzle to move along a set path in response to the instruction of the controller, so that the nozzle sprays bio-ink along the set path.

9. A print control method applied to the biological 3D printer of claim 7 or 8, characterized in that, The method comprises the following steps: constructing a three-dimensional model of a to-be-printed object; dividing the three-dimensional model into functional structures, filling different bio-ink cavities with corresponding bio-ink corresponding to different functional structures, each of the functional structures matching at least one bio-ink; regulating the printing nozzle to print the to-be-printed object, and driving the corresponding bio-ink cavity to supply bio-ink to the nozzle when printing any of the functional structures.

10. The print control method according to claim 9, characterized by, The functional structure includes at least a hard tissue component and a soft tissue component, the body defining at least a first bio-ink chamber filled with a first viscosity material and a second bio-ink chamber filled with a second viscosity material, the first viscosity material having a viscosity less than the second viscosity material; In response to the print head being ready to print the soft tissue component, the first bio-ink chamber is driven to supply the first viscosity material to the nozzle; In response to the print head being ready to print the hard tissue component, the second bio-ink chamber is driven to supply the second viscosity material to the nozzle. ​

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