A multi-jet based soft material synchronous printing method

Abstract

The application discloses a kind of soft material synchronous printing methods based on multiple spray heads, comprising: adjusting mobile device, so that the end of all spray heads is in the same horizontal plane and all points to the same point in space;With several spray heads as a group printing, a group of spray head group drops into suspended medium, and extrudes biological ink while moving in parallel, and biological ink collision realizes close fitting, forms filament;When any spray head group occurs physical interference, switch new spray head group, and the end of all spray heads is in the same horizontal plane and all points to the same point in space;When the structure in the same vertical direction is printed, switch spray head group, and according to the height of the printed filament, raise the spray head, repeat the printing process until the three-dimensional printing sample is completely printed.The application controls the resolution and topographic features of the printed structure by adjusting the printing speed and the rheological properties of the suspended medium, ensuring effective adhesion between different biological soft materials / layer and high printing fidelity.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological manufacturing, in particular to a soft material synchronous printing method based on multiple nozzles. BACKGROUND

[0002] Biological 3D printing is a manufacturing method that uses 3D printing means to manufacture a biological functional structure with individualization according to the requirements of biomorphology, biological function, cell growth microenvironment, etc. When a three-dimensional structure is constructed by biological 3D printing, a high-rigidity biological ink is needed to support itself to maintain shape fidelity, which may subsequently damage cell viability, migration or function. In order to solve the contradiction between printability and biocompatibility, a new type of 3D printing technology based on the deposition of biological ink in a support groove is developed, which is called embedded printing. Through the structural support provided by the yield stress of the suspension medium and the self-healing ability of the medium, low-rigidity biological ink can be printed and accurately and continuously deposited in the suspension medium.

[0003] Compared with the 3D printing process of biological ink in air, the suspension medium has greater viscous effect due to its high viscosity, which interacts with the support ability and self-recovery. The filament printed in the suspension medium can maintain the printed topography and be accurately fixed at the extrusion position, so when the printed filament line width and the distance set by the trajectory cannot be accurately matched, there will be a situation that the two filaments printed in succession cannot be fused together laterally. A simple and commonly used solution strategy is to design the printed adjacent filaments to overlap in space to ensure that they can be connected to each other. The distance between the designed adjacent printing paths will be less than the width of the printed filament to achieve better lateral adhesion of adjacent filaments. For complex structures, the overlap of filaments may cause uncontrolled stacking and extrusion of adjacent filaments and endanger the spatial distribution of different materials in the printed structure. It is difficult to balance the adhesion of multi-layer soft materials and the topography fidelity, which limits the further application of biological 3D printed structures. SUMMARY

[0004] In view of the deficiencies of the prior art, the present application provides a soft material synchronous printing method based on multiple nozzles, which can construct a three-dimensional multi-layer complex soft material structure with good topography fidelity and bonding strength in the suspension medium.

[0005] The specific technical solutions are as follows:

[0006] A method for synchronous printing of soft materials based on multiple printheads is implemented using a multi-printhead printing system. The multi-printhead printing system includes: a printhead assembly, a suspension medium container, and a moving device. The printhead assembly contains multiple printheads with identical structures, and the printhead tip angle is adjustable. The printhead assembly is fixed to the moving device, which can move independently in three-dimensional space. The suspension medium container is located directly below the printhead assembly. Each printhead is filled with a bio-soft material as bio-ink, and the suspension medium container is filled with a suspension medium.

[0007] The method for simultaneous printing of soft materials based on multiple nozzles specifically includes the following steps:

[0008] Step 1: Adjust the moving device so that the ends of all nozzles are on the same horizontal plane and all point to the same point in space;

[0009] Step 2: Printing is performed by grouping several printheads together. The moving device is adjusted so that a group of printheads descends into the suspension medium. The printheads move in parallel in the suspension medium while extruding bio-ink. The extruded bio-ink collides together to achieve close adhesion and forms filaments as the printheads move.

[0010] Step 3: When any printhead group experiences physical interference, switch to a new printhead group, so that the new printhead group replaces the positions of each printhead in the original printhead group, and the bio-ink in the newly replaced printhead is the same as the bio-ink in the original printhead; the ends of all printheads in the new printhead group are on the same horizontal plane and all point to the same point in space.

[0011] Step 4: After the structure in the same vertical direction is printed, switch the nozzle group and raise the nozzle according to the height of the printed filament. Repeat the printing process of Step 2 and Step 3 until the 3D printed sample is completely printed.

[0012] Furthermore, the bio-soft material includes: gelatin, sodium alginate, chitosan, methacrylic anhydride gelatin, and collagen.

[0013] Furthermore, the suspension medium is any one of nano-clay, carbomer, or a mixture of PF-127 and H-HPMC.

[0014] Furthermore, printing is performed using two printheads as a group, with different bio-ink materials in the two printheads.

[0015] Furthermore, the collision patterns of the bio-ink include center-to-center collisions and eccentric collisions.

[0016] Furthermore, the speed range of the parallel movement of the nozzle assembly is 1-20 mm / s.

[0017] Further, the nozzle adopts a bent needle head, and the outer diameter of the needle head is 0.31mm-1.08mm.

[0018] The present application has the following advantages:

[0019] (1) The present application utilizes the rheological properties of the suspending medium and the dynamics of the bio-ink extrusion process to make the bio-inks extruded from different nozzles collide together to form a close fit during the extrusion process, and controls the resolution and topological features of the printed structure by adjusting the printing speed and the rheological properties of the suspending medium.

[0020] (2) The present application adopts the method of synchronous printing in the suspending medium to construct a complex three-dimensional multi-layer structure, and makes the bio-inks extrude a certain distance and firmly fuse with each other without overlapping the printing paths of the nozzles; the extrusion and stacking behaviors of the bio-inks are controlled to ensure the effective adhesion between different bio-soft materials / layers and high printing fidelity. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 is a process schematic diagram of the present application using the soft material synchronous printing method based on multiple nozzles for printing in the suspending medium.

[0022] Figure 2 is a flow chart of the soft material synchronous printing method based on multiple nozzles of the present application.

[0023] Figure 3 is a cross-sectional fluorescent particle diagram of the filaments printed by the synchronous printing and the filaments printed by the distributed printing of the present application, wherein (i) is a cross-sectional fluorescent particle diagram of the filaments printed when the parallel motion speed of the nozzle group is 4mm / s and the proportions of PF-127 and H-HPMC are different; (ii) is a cross-sectional fluorescent particle diagram of the filaments printed when the proportion of PF-127 and H-HPMC is 10:3 and the parallel motion speed of the nozzle group is changed.

[0024] Figure 4 is a schematic diagram of a double-layer hollow straight pipe obtained by synchronous printing in the embodiment of the present application, wherein (a) is a front view and a top view of the double-layer hollow straight pipe in the suspending medium, (b) is a front view and a top view of the double-layer hollow straight pipe in deionized water, and (c) is a partial cross-sectional view of the double-layer hollow straight pipe.

[0025] Figure 5 is a schematic diagram of a double-layer hemisphere obtained by synchronous printing in the embodiment of the present application, wherein (a) is a front view and a top view of the double-layer hemisphere in the suspending medium, (b) is a front view and a top view of the double-layer hemisphere in deionized water, and (c) is a partial cross-sectional view of the double-layer hemisphere.

[0026] Figure 6Figure 1 is a schematic diagram of a double-layer Y-shaped tube obtained by simultaneous printing in an embodiment of the present application, wherein (a) is a front view and a top view of the double-layer Y-shaped tube in a suspension medium, (b) is a front view and a top view of the double-layer Y-shaped tube in deionized water, and (c) is a partial sectional view of the double-layer Y-shaped tube.

[0027] Figure 7 Figure 2 is a schematic diagram of a double-layer structure similar to small intestine obtained by simultaneous printing in an embodiment of the present application, wherein (a) is a front view of the printed sample in a suspension medium, (b) is a front view of the printed sample in deionized water, (c) is a sectional view of part A of the printed sample, and (d) is a sectional view of part B of the printed sample.

[0028] Figure 8 Figure 3 is a schematic diagram of a double-layer structure similar to liver obtained by simultaneous printing in an embodiment of the present application, wherein (a) is a front view of the printed sample in a suspension medium, (b) is a front view of the printed sample in deionized water, (c) is a sectional view of part A of the printed sample, and (d) is a sectional view of part B of the printed sample.

[0029] Figure 9 Figure 4 is a schematic diagram of a process for detecting the mechanical properties of the bonding strength of a T-shaped sample obtained by simultaneous printing and step-by-step printing, respectively, in an embodiment of the present application.

[0030] Figure 10 Figure 5 is a schematic diagram of a curve of the tensile force versus displacement in the detection results of the mechanical properties of the bonding strength of a T-shaped sample.

[0031] Figure 11 Figure 6 is a schematic diagram of the detection results of the mechanical properties of the bonding strength of a T-shaped printed sample under different manufacturing methods.

[0032] In the figure, the nozzle 1, the first nozzle 11, the second nozzle 12, the third nozzle 13, the fourth nozzle 14, the suspension medium 2, the first bio-ink 31, and the second bio-ink 32. DETAILED DESCRIPTION

[0033] The present application will be described in detail below with reference to the accompanying drawings and preferred embodiments, and the objects and effects of the present application will become more apparent. The following further describes the present application in detail with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely intended to explain the present application and are not intended to limit the present application.

[0034] As Figure 1As shown, the present application is realized based on a multi-jet printing system, which comprises a jet assembly 1, a suspension medium container, a moving device (not shown in the figure), the jet assembly 1 comprising four structurally identical jets: a first jet 11, a second jet 12, a third jet 13, and a fourth jet 14. The first jet 11, the second jet 12, the third jet 13, and the fourth jet 14 are respectively fixedly installed on the moving device with independent three degrees of freedom, all the four jets are needle heads with small outer diameters, and the needle head angles are adjustable, the ends of different jets can have direct contact or no direct contact; the four jets are respectively filled with biological soft materials, which are used as biological ink for printing. The biological soft material refers to a viscoelastic material with an elastic modulus less than 5000 Pa, and the optional biological soft materials include: gelatin, sodium alginate, chitosan, methacrylated gelatin, and collagen, and the biological soft materials filled in different jets can be the same or different, which is determined by the requirements of the three-dimensional printing sample to be printed. When filling, the jets of the first jet 11, the second jet 12, the third jet 13, and the fourth jet 14 are all placed towards the vertical upward direction to make the bubbles float up, and after there are no bubbles in the needle cylinder, they are fixedly installed on the moving device according to the requirements.

[0035] The suspension medium 2 is arranged in the suspension medium container, in the present embodiment, the suspension medium 2 is arranged in a transparent box. The suspension medium 2 is selected from nano-clay, carbomer, or a mixture of PF-127 and H-HPMC. When arranging, the prepared suspension medium 2 at high temperature is poured into the transparent box, sealed by a sealing film and placed in the air for a period of time, so that the bubbles in the suspension medium 2 float up to form a clear homogeneous fluid.

[0036] In the present embodiment, the first jet 11, the second jet 12, the third jet 13, and the fourth jet 14 all adopt bent-angle needle heads, the outer diameter of the needle head is 0.31mm-1.08mm; the first jet 11 and the third jet 13 are filled with the first biological ink 31, which is methacrylated gelatin; the second jet 12 and the fourth jet 14 are filled with the second biological ink 32, which is sodium alginate; and the suspension medium 2 is selected from a mixture of PF-127 and H-HPMC. Two kinds of polystyrene microspheres with different fluorescence excitation wavelengths are respectively and uniformly mixed into the first ink 31 and the second ink 32, and the diameter of the polystyrene microspheres is 4 microns.

[0037] As shown in Figure 1 , Figure 2 The soft material synchronous printing method based on the multi-jet is specifically as follows:

[0038] Step one: adjust the moving device, select the end of one jet as the origin and keep it still, adjust the spatial positions of the other jets and the needle head angles, so that the ends of all the jets are in the same horizontal plane and all point to the same point in space.

[0039] Step two: first, the first nozzle 11 and the fourth nozzle 14 are used as a group to print, the moving device is adjusted so that the first nozzle 11 and the fourth nozzle 14 are lowered into the suspension medium 2, the first nozzle 11 and the fourth nozzle 14 move in parallel in the suspension medium 2, the speed range of the parallel movement of the two nozzles is 1-20 mm / s. At the same time, the first nozzle 11 and the fourth nozzle 14 extrude the first bio-ink 31 and the second bio-ink 32 respectively, the extruded bio-ink is sprayed a distance on the extension line of the nozzle, in the process of spraying, the first bio-ink 31 and the second bio-ink 32 collide together to realize close adhesion, and form a filament with the movement of the nozzle; wherein, the collision form of the bio-ink includes concentric collision and eccentric collision, and close adhesion refers to the existence of overlapping parts in the profile of adjacent filaments.

[0040] Step three: when the first nozzle 11 and the fourth nozzle 14 printed synchronously physically interfere with each other, the nozzle group is switched, specifically:

[0041] The moving device is adjusted to correspond to the switching of the second nozzle 12 and the third nozzle 13, so that the second nozzle 12 replaces the fourth nozzle 14 and the third nozzle 13 replaces the first nozzle 11. After the switching of the nozzle group, the ends of the different nozzles used for printing still need to point to a spatial point. If the second nozzle 12 and the third nozzle 13 physically interfere with each other, the nozzle group is switched again.

[0042] Step four: after the structure in the same vertical direction is printed, the nozzle group is switched, and the nozzle is raised according to the height of the printed filament, and the printing process of steps two and three is repeated until the three-dimensional printed sample is completely printed. During the printing process, the nozzle group is switched and the material is stacked in the vertical direction, so that the three-dimensional multi-layer structure is stacked and constructed.

[0043] As shown in Figure 3 FIG. 4, it is a cross-sectional fluorescent particle diagram of the filaments printed synchronously and the filaments printed distributively in this embodiment, which is taken by a confocal microscope. Figure 3 (i) is a cross-sectional fluorescent particle diagram of the filaments printed when the nozzle moves in the suspension medium 2 with different proportions of PF-127 and H-HPMC at a speed of 4 mm / s, wherein the first row is printed by using the synchronous printing method of the present application, and the second row is printed by using a single nozzle. Figure 3 (ii) is a cross-sectional fluorescent particle diagram of the filaments printed when the nozzle moves in the suspension medium 2 with a proportion of 10:3 of PF-127 and H-HPMC at different parallel movement speeds, wherein the first row is printed by using the synchronous printing method of the present application, and the second row is printed by using a single nozzle.

[0044] The average aspect ratio of the filaments printed by the two nozzles in simultaneous printing is taken as the aspect ratio of the synchronously printed filament; similarly, the average width of the filaments printed by the two nozzles in simultaneous printing is taken as the width of the synchronously printed filament. Figure 3 It can be seen that changing the synchronous printing speed and the rheological properties of the suspension medium 2 (i.e., the ratio of PF-127 to H-HPMC) alters the width and aspect ratio of the synchronously printed filaments. Comparing the aspect ratio and width of the synchronously printed filaments with those of filaments printed from a single printhead shows that, under the same printing speed and rheological properties of the suspension medium 2, the synchronously printed filaments maintain almost the same morphological characteristics as those printed from a single printhead. At a PF-127 to H-HPMC ratio of 10:3 and a printing speed of 12 mm / s, the minimum width of the synchronously printed filaments is approximately 100 μm, and the aspect ratio is close to 1, ensuring the printing result matches the trajectory planning.

[0045] In summary, the width of the printed filament is jointly regulated by the nozzle movement speed and the extrusion air pressure. Under conditions of high printing speed and low viscosity, by selecting appropriate printing parameters (i.e., nozzle movement speed and extrusion air pressure) and suspension medium, we can still print high-precision filaments with good positional fidelity. This is helpful for the three-dimensional manufacturing of microstructures and also enables us to manufacture complex heterogeneous structures.

[0046] like Figures 4-6 The figures show schematic diagrams of the double-layer hollow straight tube, double-layer hemisphere, and double-layer Y-shaped tube obtained by simultaneous printing in embodiments of the present invention. As can be seen from the figures, no delamination was observed during the process of transferring the printed sample from the suspension medium 2 to deionized water for cleaning. In particular, it can be clearly seen from the top view that two layers of different colors are combined to form a uniform multilayer structure. To further evaluate the adhesion between the multilayer structures and the printing accuracy, the printed sample was cut along the axial direction, and the cross-section was observed using a bright-field microscope. From the cross-sectional view, it was observed that the two layers of the structure are tightly connected together, while maintaining a clear interface between the two layers, and there is no residual suspension medium 2 between the two layers; the thickness of the two layers is the same, with a measured value of approximately 200 μm, proving that the selection of printing parameters (i.e., nozzle movement speed and extrusion air pressure) can precisely control the accuracy of the printed sample and maintain good consistency with the design parameters.

[0047] like Figure 7 , Figure 8As shown, the method of simultaneous printing is used to print double-layer structures similar to small intestine and liver, respectively, in which the structure of the intestine is similar to the real organ's wrinkle structure. The cross-section of the two human organ models is enlarged, and the results show that the two-layer structure achieves good fitting. Therefore, for complex structures, the simultaneous printing method used in the present application can also accurately print double-layer structures with optimal fitting and morphology.

[0048] As shown in Figure 9 The prepared T-shaped samples were subjected to peeling tests to study the adhesion strength between the simultaneously printed samples. As shown in Figure 10 , Figure 11 The results of the peeling test were compared with the cast samples and the step-by-step printed samples, and the peeling test results of the three groups of samples showed different failure types. For the cast and simultaneously printed samples, tensile failure occurred on one of the clamps before the sample reached the maximum test distance, indicating that the bonding strength between the two biological soft materials in these two cases was greater than the material strength. For the step-by-step printed samples, the two soft materials gradually peeled off, and no tensile failure was observed before reaching the maximum test range, which means that for the step-by-step printed samples, the bonding strength is less than the strength of the biological soft materials themselves. During the test, the normalized maximum bonding force relative to the sample width was selected as the evaluation feature of the interfacial strength. The results prove that under the same trajectory, the bonding strength of the simultaneously printed samples is significantly greater than that of the samples printed by step-by-step printing. This may be due to the fact that during the step-by-step printing process, the two biological soft materials are mixed with the suspending medium and produce discrete interfaces; the suspending medium 2 used in the present application is removed after printing and cannot be cross-linked, so it does not provide any tensile strength; therefore, if any suspending medium remains between the inner and outer layers of the printed structure, the bonding strength will be reduced. The simultaneous printing method proposed in the present application better solves the current structural integrity problem of multi-layer structures.

[0049] The present application utilizes the rheological properties of the suspending medium and the dynamics of the biological ink extrusion process. During the printing process, the suspending medium 2 is subjected to a decrease in viscosity in the yield region, and the biological ink extrusion in this region is affected by dynamics and is ejected a certain distance along the nozzle extrusion direction. Under the premise that the nozzle tip is adjusted to point to the same point in space, the biological ink is made to collide together to form a tight fit without overlapping the nozzle printing path. By adjusting the printing speed and the rheological properties of the suspending medium, the resolution and topological features of the printed structure are controlled, the extrusion and stacking behavior of the biological ink is controlled, and the effective adhesion between different biological soft materials / layers and high printing fidelity are ensured.

[0050] Those skilled in the art can understand that the above description is only the preferred examples of the present application and is not used to limit the present application, and although the present application is described in detail with reference to the foregoing examples, those skilled in the art can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacements for part of the technical features. Any modification, equivalent replacement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A multi-jet based method for simultaneous printing of soft materials, characterized in that, The application discloses a multi-jet printing system and a soft material synchronous printing method based on the same. The multi-jet printing system comprises a nozzle assembly, a suspension medium container and a moving device. The nozzle assembly comprises a plurality of nozzles with the same structure and adjustable nozzle tip angles. The nozzle assembly is fixed on the moving device which can move independently in a three-dimensional space. The suspension medium container is located directly below the nozzle assembly. Each nozzle is filled with a biological soft material as a biological ink. The suspension medium container is filled with a suspension medium.

2. The multi-jet based soft material simultaneous printing method of claim 1, wherein, The soft material synchronous printing method based on the multi-jet printing system comprises the following steps.

3. The multi-jet based soft material simultaneous printing method of claim 1, wherein, Step 1: Adjust the moving device so that the tips of all nozzles are on the same horizontal plane and point to the same point in space.

4. The multi-jet based soft material simultaneous printing method of claim 1, wherein, Step 2: Print with several nozzles as a group.

5. The multi-jet based soft material simultaneous printing method of claim 1, wherein, Adjust the moving device so that the nozzle group is lowered into the suspension medium.

6. The multi-jet based soft material simultaneous printing method of claim 1, wherein, The nozzles move in parallel in the suspension medium while extruding the biological ink. The extruded biological ink collides together to achieve close adhesion and forms a filament with the movement of the nozzle group. Step 3: When any nozzle group is physically interfered, switch to a new nozzle group. The new nozzle group replaces the positions of the nozzles in the original nozzle group. The biological ink in the new nozzle group is the same as that in the original nozzle. The tips of all nozzles in the new nozzle group are on the same horizontal plane and point to the same point in space. Step 4: When the structure in the same vertical direction is printed, switch the nozzle group and raise the nozzles according to the height of the printed filament. Repeat the printing process of steps 2 and 3 until the three-dimensional printing sample is completely printed. The suspension medium is any one of nano-clay, carbomer or a mixture of PF-127 and H-HPMC. The biological soft material includes any one of gelatin, sodium alginate, chitosan, methacrylanated gelatin and collagen. Two nozzles are used as a group for printing. The biological ink materials in the two nozzles are different. The collision forms of the biological ink include concentric collision and eccentric collision. The speed range of the parallel movement of the nozzle group is 1-20 mm / s. The nozzle adopts a bent needle with an outer diameter of 0.31-1.08 mm.

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