A coaxial needle, three-dimensional printing method and application thereof

Abstract

The coaxial needle provided by the present application includes a core needle and a shell needle arranged around the core needle, the core needle extends one end distance from the shell needle, the core needle can extrude a core sacrificial ink material, and the shell needle can extrude a shell ink material. The above coaxial needle can form a bifurcated structure by using a material with similar rheological properties to puncture the pipe wall on a section of the printed pipe structure as needed and then fill and heal it. In addition, the present application also provides a three-dimensional printing method based on the above coaxial needle and its application.

Description

Technical Field

[0001] The present invention relates to the field of advanced manufacturing technology, and in particular to a coaxial needle, a three-dimensional printing method and applications thereof. Background Art

[0002] As the most basic unit of the three-dimensional structure in nature, the tubular structure has a diameter ranging from a few microns to tens of meters. Through the sacrificial template method, the construction of a three-dimensional structure with interconnected pipes can be realized. However, the pipe formed after the template is sacrificed is misaligned at the bifurcation, that is, the central axis of the bifurcated pipe does not cross, which easily causes abnormal flow rate at the bifurcation of the fluid. At the same time, since the sacrificial template method often requires the participation of violent chemical reactions, its application in the biomedical field has great limitations. For existing three-dimensional printing technology, although the construction of tubular interconnected structures can be realized through extrusion printing (single line stacking or single line spiral winding), its poor sealing and long time-consuming disadvantages make this method difficult to promote. The use of coaxial needles has realized the direct manufacturing of tubular structures on demand, but the constructed hollow pipes cannot be interconnected, that is, they are series structures, and it is impossible to obtain interconnected mesh structures, and it cannot provide a three-dimensional environment conducive to fluid transmission.

[0003] Therefore, how to directly coaxially print a parallel structure with interconnected hollow channels and accurately control the merging and bifurcation of different channels in three-dimensional dimensions is a major challenge currently faced by coaxial three-dimensional printing technology in the construction of complex structures.

[0004] Although the current coaxial 3D printing technology has achieved on-demand manufacturing, the hollow tubular tissues constructed cannot achieve mutual penetration or connection of the pipes, and cannot provide a 3D support environment conducive to fluid transmission. The main reason is that the needle head of the existing coaxial needle is divided into a flat end, which does not effectively utilize the effect brought by the needle structure in printing. Summary of the invention

[0005] In view of this, it is necessary to provide a coaxial needle that can accurately print different tubular parallel structures according to actual needs.

[0006] To solve the above problems, this application adopts the following technical solutions:

[0007] The present application provides a coaxial needle, comprising a core needle and a shell needle arranged around the core needle, wherein the core needle extends one end distance further than the shell needle, the core needle can extrude a core sacrificial ink material, and the shell needle can extrude a shell ink material.

[0008] In some embodiments, there is at least one shell needle, which are arranged around each other.

[0009] In some embodiments, the core needle extends out of the shell needle by a distance ranging from 1 / 3 to 2 / 3 of the difference between the interlayer diameters of the core needle and the adjacent shell needle.

[0010] In some of the embodiments, the core sacrificial ink material is a degradable material having shear-to-thin rheological properties, and the degradable material includes but is not limited to at least one of shear-to-thin hydrogel or inorganic nanoclay or F127 or sodium alginate or thermosensitive glue or gelatin or carbomer or hyaluronic acid or artificial polymers.

[0011] In some of the embodiments, the inorganic nanoclay-based hydrogel uses inorganic nanoclay as a main material, with a content of 3% to 20%, and the remaining component is water.

[0012] In some of these embodiments, the shell ink material includes at least one of gelatin-based hydrogel or double-bond modified hyaluronic acid or sodium alginate or polyvinyl alcohol.

[0013] In some of the embodiments, the gelatin-based hydrogel is synthesized from a gelatin precursor, including 5% to 40% by mass of the gelatin precursor, 0.05% to 1% by mass of an ultraviolet light initiator, and the balance of water.

[0014] On the other hand, the present application also provides a three-dimensional printing method of the coaxial needle, comprising the following steps:

[0015] Design a corresponding printing program on the 3D printing platform according to the structure to be printed;

[0016] The core needle extrude core sacrificial ink material to construct a sacrificial structure according to the printing procedure, and the shell needle extrude shell ink material to construct an overall scaffold structure according to the printing procedure;

[0017] The overall support structure is cured;

[0018] The core sacrificial ink material in the solidified overall support structure is dissolved to obtain a printed structure.

[0019] In some of the embodiments, a material supply cavity is provided in the channels of the core needle and the shell needle.

[0020] In some of the embodiments, in the step of curing the overall support structure, the curing includes ultraviolet light curing, thermal polymerization, or ionic cross-linking.

[0021] In some of the embodiments, in the step of dissolving the core sacrificial ink material in the solidified overall support structure to obtain the structure to be printed, the dissolving method includes soaking in water or heating or using a solvent for dissolving, and the solvent includes sodium citrate.

[0022] In some of the embodiments, the structure to be printed is a mesh-like interconnected hollow channel structure.

[0023] In addition, the present application also provides an application of a three-dimensional printing method, which can be used for printing a variety of cells.

[0024] By adopting the above technical solution, the technical effects achieved by the present invention are as follows:

[0025] The coaxial needle provided in the present application includes a core needle and a shell needle arranged around the core needle, the core needle extends one end distance longer than the shell needle, the core needle can extrude a core sacrificial ink material, and the shell needle can extrude a shell ink material. The above-mentioned coaxial needle can form a cross or bifurcated structure by using a type of material with similar rheological properties to puncture the pipe wall on a section of the pipe structure that has been printed and then fill and heal it as needed.

[0026] The coaxial needle provided in the present application can be used for three-dimensional printing. According to the printing program, the core needle extrude the core sacrificial ink material to construct a sacrificial structure. According to the printing program, the shell needle extrude the shell ink material to construct an overall support structure. The overall support structure is solidified, and the core sacrificial ink material in the solidified overall support structure is dissolved to obtain a hollow pipe network three-dimensional support, thereby realizing direct coaxial printing of a parallel structure in which hollow channels are interconnected, and accurately controlling the merging and bifurcation of different channels in three-dimensional dimensions.

[0027] The three-dimensional printing method of the coaxial needle provided by the present invention can be used to construct human or animal tissues or organs in vitro. Cells can be mixed in biological ink, and the distribution of cells in the three-dimensional scaffold can be accurately controlled. The printed cells can have a very high concentration and can contact each other, effectively solving the problem that cells cannot be distributed in the tube wall by the sacrificial template method. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments of the present invention or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0029] Figure 1 A schematic structural diagram of a coaxial needle provided in an embodiment of the present invention.

[0030] Figure 2 A flowchart of the steps of the three-dimensional printing method of the coaxial needle provided in an embodiment of the present application.

[0031] Figure 3 This is a T-shaped structure designed by a program, the moving direction of the coaxial printing needle and the actual diagram of the printed structure provided in Example 1 of the present application.

[0032] Figure 4 Verification of the connectivity of the T-structured pipeline printed by the parallel coaxial printing method provided in Example 1 of the present application.

[0033] Figure 5 A physical diagram of the Y-shaped structure, the moving direction of the coaxial printing needle and the printed structure designed by a program provided in Example 2 of the present application.

[0034] Figure 6 Verification of the connectivity of the Y-shaped pipe printed by the parallel coaxial printing method provided in Example 2 of the present application. DETAILED DESCRIPTION

[0035] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, and should not be construed as limiting the present invention.

[0036] In the description of the present invention, it is necessary to understand that the terms "upper", "lower", "horizontal", "inside", "outside", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0037] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0038] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments.

[0039] See also Figure 1, is a schematic diagram of the structure of a coaxial needle provided by an embodiment of the present invention, comprising a core needle 110 and a shell needle 120 arranged around the core needle 110, the axes of the core needle 110 and the shell needle 120 coincide, the core needle 110 extends one end distance from the shell needle 120, the core needle 110 can extrude a core sacrificial ink material 130, and the shell needle 120 can extrude a shell ink material 140. The specific implementation of each component is described in detail below.

[0040] In some embodiments, there is at least one shell needle 120, which are arranged around each other.

[0041] It can be understood that the number of layers of the shell needle 120 can be designed according to actual needs.

[0042] In some embodiments, the core needle 110 extends from the shell needle 120 by a distance of 1 / 3 to 2 / 3 of the diameter difference between the core needle 110 and the adjacent shell needle 120. Further, the printing effect is better when the core needle 110 extends from the shell needle 120 by a distance of half the diameter difference between the core needle 110 and the adjacent shell needle 120, and in practice, printing can still be completed with a certain difference between these values.

[0043] In some of the embodiments, the core needle and the shell needle may be made of metal, plastic or other materials, depending on actual use requirements.

[0044] In some embodiments, the core sacrificial ink material 130 is a degradable material having shear-thinning rheological properties.

[0045] Furthermore, the degradable material includes but is not limited to at least one of sheared to dilute hydrogel or inorganic nanoclay or F127 or sodium alginate or thermosensitive gel or gelatin or carbomer or hyaluronic acid or artificial polymer.

[0046] Furthermore, the inorganic nanoclay-based hydrogel uses inorganic nanoclay as a main material, with a content of 3% to 20%, and the remaining component is water.

[0047] In some of the embodiments, the shell ink material 140 includes at least one of gelatin-based hydrogel or double-bond modified hyaluronic acid or sodium alginate or polyvinyl alcohol.

[0048] It can be understood that since the gelatin-based hydrogel is a shear-thin hydrogel and the hydrogel macromolecule modified with a double bond is used as a cross-linking agent, the cross-linking agent may be other double-bond modified macromolecules.

[0049] Furthermore, the gelatin-based hydrogel is synthesized from a gelatin precursor, including 5% to 40% by mass of the gelatin precursor, 0.05% to 1% by mass of an ultraviolet light initiator and the balance of water.

[0050] It can be understood that the present application uses methacrylated gelatin as the shell ink material 140 to carry cells and can be applied to tissue engineering.

[0051] The coaxial needle provided in the present application, wherein the core needle can extrude a core sacrificial ink material, and the shell needle can extrude a shell ink material, can form a bifurcated structure by using a class of materials with similar rheological properties to puncture the tube wall on a section of the printed pipe structure as needed and then fill and heal it.

[0052] See also Figure 2 The three-dimensional printing method of the coaxial needle provided in the embodiment of the present application comprises the following steps:

[0053] Step S110: designing a corresponding printing program on a three-dimensional printing platform according to the structure to be printed.

[0054] It can be understood that the software required for building the 3D printing platform includes but is not limited to Rhino, Grasshopper, GhPython, and GeSiM. The program can be designed according to different needs to print out 3D tubular parallel structures of different morphologies.

[0055] Step S120: the core needle extrude core sacrificial ink material to construct a sacrificial structure according to the printing procedure, and the shell needle extrude shell ink material to construct an overall support structure according to the printing procedure.

[0056] It is understandable that before printing begins, the position of each needle used in printing needs to be calibrated, and the bottoms of all needles connected to the channels are on the same horizontal line. The position of the needle on the printing platform is adjusted based on the needle of the first bracket material group to be discharged.

[0057] Furthermore, due to the coaxial needle, the core needle from the outside to the inside extends one end distance longer than the shell needle. By using the improved needle, the printing program design can be the same as the direct single-axis printing of the outermost needle, and the extruded core sacrificial ink material of the core needle can be automatically connected at the intersection (see Figure 1 ); The first line printed by the shell needle is the same as that printed by an ordinary coaxial needle. A designed line is written on the printing platform. Starting from the second line, if there is a bifurcated structure, the coaxial needle can be directly positioned at the intersection or the end of the branch, and then written to the end of the branch or the intersection; for the annular structure, the initial point and the end point can be set overlapping to complete the connection of the lines.

[0058] It can be understood that since there can be multiple shell needles, and the material extruded by the shell needles can be a single component or a composition containing different materials and different proportions, a three-dimensional composite integral bracket structure composed of different levels of materials can be printed.

[0059] In some of the embodiments, a material supply cavity is provided in the channels of the core needle and the shell needle.

[0060] In some of the embodiments, the needles connected to the various channels can move up, down, left, and right relatively without being restricted by each other.

[0061] It can be understood that during the printing process, the printing substrate does not move, and each time a line is printed, all the needles move upward, and the upward movement distance or speed is related to the needle diameter and material properties.

[0062] Step S130: curing the overall support structure.

[0063] In some of the embodiments, in the step of curing the overall support structure, the curing includes ultraviolet light curing, thermal polymerization, or ionic cross-linking.

[0064] It can be understood that the UV curing method is relatively gentle and causes little damage to cells.

[0065] Step S140: dissolving the cured core sacrificial ink material in the overall support structure to obtain a printed structure.

[0066] In some of the embodiments, in the step of dissolving the core sacrificial ink material in the solidified overall support structure to obtain the structure to be printed, the dissolving method includes soaking in water or heating or using a solvent for dissolving, and the solvent includes sodium citrate.

[0067] In some of the embodiments, the structure to be printed is a network of interconnected hollow channel structures, and according to different program designs, three-dimensional tubular parallel structures with different morphologies can be printed.

[0068] The three-dimensional printing method provided in the present application can extrude the core sacrificial ink material according to the core needle of the printing program to construct a sacrificial structure, extrude the shell ink material according to the shell needle of the printing program to construct an overall support structure, solidify the overall support structure, and dissolve the core sacrificial ink material in the solidified overall support structure to obtain a hollow pipe network three-dimensional support, thereby realizing direct coaxial printing of a parallel structure in which hollow channels are interconnected, and accurately controlling the merging and bifurcation of different channels in three-dimensional dimensions.

[0069] The three-dimensional printing method provided in the present application can be used for printing a variety of cells and can be used to construct human or animal tissues or organs in vitro.

[0070] Furthermore, cells may be mixed in the extruded materials of the core needle 110 and the shell needle 120 .

[0071] Furthermore, when used for biological 3D printing, cells are mixed into the material and the entire printing process is completed in a biosafety cabinet to ensure that the overall operating environment is sterile.

[0072] The three-dimensional printing method of the coaxial needle provided by the present invention can be used to construct human or animal tissues or organs in vitro. Cells can be mixed in biological ink, and the distribution of cells in the three-dimensional scaffold can be accurately controlled. The printed cells can have a very high concentration and can contact each other, effectively solving the problem that cells cannot be distributed in the tube wall by the sacrificial template method.

[0073] The above technical solution of the present invention will be described in detail below in conjunction with embodiments.

[0074] Example 1

[0075] A. The main structure of the shell structure is gelatin-based hydrogel, the components of the hydrogel precursor are 15% of double-bond-modified gelatin macromolecules, 0.2% of ultraviolet light initiator, and the remaining components are water.

[0076] B. Inorganic nanoclay-based hydrogel is used as the core sacrificial structure, and the mass fraction of inorganic nanoclay is 7%.

[0077] C. According to the printing procedure, the core needle extrude the inorganic nanoclay-based hydrogel to construct the sacrificial structure, and according to the printing procedure, the shell needle extrude the gelatin-based hydrogel to construct the overall scaffold structure.

[0078] Construction of DT font structure: Verify the ability to write horizontally by vertically piercing from the bifurcation point, and the moving direction of the coaxial printing needle (see Figure 3 , where the circle is the starting point of the needle's falling movement, the arrow is the end point of the needle's lifting movement, the black part is the first moving path, and the gray part is the second moving path).

[0079] Specifically, the coaxial needle moves to the starting point and falls, continuously applying pressure in the two barrels to squeeze out the core ink and the shell ink at the same time; at the same time, the coaxial needle moves along the black line or gray line to the arrow at a certain speed, stops applying pressure and lifts the needle to complete printing.

[0080] E. After the composite scaffold is printed, it can be placed in a UV cross-linker for photocuring for 120 seconds to make the gel plastic.

[0081] F. After cross-linking, the three-dimensional composite scaffold is taken out and soaked in water, or placed in a shaker to slowly release the sacrificial inorganic nanoclay wrapped in the gelatin shell structure to obtain a true hollow tubular three-dimensional composite scaffold ( Figure 3 ).

[0082] G. Finally, red ink is injected into the hollow pipe structure to verify the connectivity and tightness of the pipe ( Figure 4 , perfuse from the main channel in air to verify the patency from the main channel to the branch channel).

[0083] Example 2

[0084] A. The main structure of the shell structure is gelatin-based hydrogel, the components of the hydrogel precursor are 15% of double-bond-modified gelatin macromolecules, 0.2% of ultraviolet light initiator, and the remaining components are water.

[0085] B. Inorganic nanoclay-based hydrogel is used as the core sacrificial structure, and the mass fraction of inorganic nanoclay is 7%.

[0086] C. According to the printing procedure, the core needle extrude the inorganic nanoclay-based hydrogel to construct the sacrificial structure, and according to the printing procedure, the shell needle extrude the gelatin-based hydrogel to construct the overall scaffold structure.

[0087] Construction of DY font structure: Verify the ability to write horizontally from the end of the branch to the intersection, and the moving direction of the coaxial printing needle (see Figure 5 , the circle is the starting point of the needle's falling movement, the arrow is the end point of the needle's lifting movement, the black part is the first moving path, and the gray part is the second moving path).

[0088] Specifically, the coaxial needle moves to the starting point and falls, and continues to apply pressure in the two barrels to squeeze out the core ink and the shell ink at the same time. At the same time, the coaxial needle moves along the black or gray line at a certain speed to the arrow, stops applying pressure and lifts the needle to complete printing.

[0089] E. After the composite scaffold is printed, it can be placed in a UV cross-linker for photocuring for 120 seconds to make the gel plastic.

[0090] F. After cross-linking, the three-dimensional composite scaffold is taken out and soaked in water, or placed in a shaker to slowly release the sacrificial inorganic nanoclay wrapped in the gelatin shell structure to obtain a true hollow tubular three-dimensional composite scaffold ( Figure 5 ).

[0091] G. Finally, red ink is injected into the hollow pipe structure to verify the connectivity and tightness of the pipe ( Figure 6 , and fill it to verify the connectivity and sealing of the pipeline. The red liquid is dyed water).

[0092] The above are only preferred embodiments of the present invention, and only specifically describe the technical principles of the present invention. These descriptions are only for explaining the principles of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations here, any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention, and other specific implementations of the present invention that can be associated with by technicians in this field without creative labor, should be included in the scope of protection of the present invention.

Claims

1. A three-dimensional printing method of a coaxial needle, characterized in that: The coaxial needle head comprises a core needle head and a shell needle head arranged around the core needle head, the axes of the core needle head and the shell needle head coincide with each other, the core needle head extends a distance from the shell needle head, the core needle head can extrude a core sacrificial ink material, and the shell needle head can extrude a shell ink material; The core sacrificial ink material is a degradable material with shear-thin rheological properties; The degradable material includes but is not limited to at least one of inorganic nano-clay-based hydrogel or sodium alginate or thermosensitive gel or gelatin or carbomer or hyaluronic acid; The shell ink material includes at least one of gelatin-based hydrogel or double-bond-modified hyaluronic acid or sodium alginate or polyvinyl alcohol; The three-dimensional printing method of the coaxial needle comprises the following steps: Design a corresponding printing program on the 3D printing platform according to the structure to be printed; The core needle extrude core sacrificial ink material to construct a sacrificial structure according to the printing procedure, and the shell needle extrude shell ink material to construct an overall scaffold structure according to the printing procedure; The overall support structure is cured; Dissolving the core sacrificial ink material in the solidified overall support structure to obtain a structure to be printed; The structure to be printed has a cross or bifurcated structure; During printing, the coaxial needle punctures the wall of a section of the pipe structure that has already been printed, continues printing, and then fills and heals to form a cross or bifurcated structure.

2. The three-dimensional printing method according to claim 1, characterized in that: The channels of the core needle and the shell needle are both provided with material supply cavities.

3. The three-dimensional printing method according to claim 1, characterized in that: In the step of curing the overall support structure, the curing includes ultraviolet light curing, thermal polymerization or ion cross-linking.

4. The three-dimensional printing method according to claim 1, characterized in that: In the step of dissolving the core sacrificial ink material in the solidified overall support structure to obtain the structure to be printed, the dissolving method includes soaking in water or heating or using a solvent for dissolving, and the solvent includes sodium citrate.

5. The three-dimensional printing method according to claim 1, characterized in that: The structure to be printed is a mesh-like interconnected hollow channel structure.

6. The three-dimensional printing method according to claim 1, characterized in that: There is at least one shell needle head, which are arranged around each other.

7. The three-dimensional printing method according to claim 1, characterized in that: The core needle head extends out of the shell needle head by a distance ranging from 1 / 3 to 2 / 3 of the difference between the interlayer diameters of the core needle head and the adjacent shell needle head.

8. The three-dimensional printing method according to claim 1, characterized in that: The inorganic nano-clay-based hydrogel uses inorganic nano-clay as a main material, the mass content of which is 3% to 20%, and the remaining component is water.

9. The three-dimensional printing method according to claim 1, characterized in that: The gelatin-based hydrogel is synthesized from a gelatin precursor, including 5% to 40% by mass of the gelatin precursor, 0.05% to 1% by mass of an ultraviolet light initiator and the balance of water.

10. An application of the three-dimensional printing method according to claim 1, characterized in that: Used for printing of various cells.

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