Method and system for producing printable objects

Abstract

The present disclosure relates to a method for printing a 3D printable object, for example for biomedical purposes, comprising: moving an ejection tip (120) of a printing element included in a printing device at least horizontally within a support material (115) such that the ejection tip forms a cavity in the support material, the support material being a complex fluid having a semi-solid gel consistency, the cavity corresponding to the shape of the 3D printable object; ejecting a printing material (110) into the cavity using the ejection tip, the printing material being comprised of a biodegradable or biostable resin or an infusion resin composite; and covering the printing material with a flow of support material after the ejection tip movement.

Description

[Technical Field]

[0001] The present disclosure relates to the production of objects manufactured using additive manufacturing. [Background technology]

[0002] In the production of 3D printed objects with a variety of shapes, shapes or portions of shapes, such as overhangs, may exist. These shapes may be significant overhangs that cannot be balanced by the main body of the printable object and may therefore collapse under gravity. Various approaches can be used to overcome this problem, including printing materials in a support bath and multichannel plotting by co-extruding a temporary (or provisional) support material with the primary printing material. The first approach generally suffers from contamination of the printed layer with bath material that prevents the layers from fusing together, insufficient support effect against gravity, and clogging of the jetting head. The second approach is limited by the need to remove the temporary support material from the actual printed object. Temporary co-extrusion systems also overcome challenges related to protecting the printable material from the negative effects of ambient air on polymerization. With the present technology, there may still be a need to print an object in multiple parts and then glue these parts together to form a single final object.

[0003] In the fabrication of tissue engineering scaffolds, implantable or orally administered drug-releasing devices, tumor cell invasion scaffolds, soft and hard tissue replacement and reconstruction, and other technical devices, geometries can actually contain overhangs, thereby limiting single-piece printing. Furthermore, when printing with bioinks containing cells or thermosensitive compounds, the high temperatures of the printing environment, including the support bath, can be harmful to the thermosensitive compounds and cells. This limitation can arise when using current bioink printing processes because some bioink and support bath materials are based on thermoplastic polymers or hydrogels with heat-sensitive viscosities. Indeed, many printing bath hydrogels may require high temperatures to achieve gel consistency and to be compatible with the printing substrate. Furthermore, if the support material hydrogel is optimized to have a viscosity that provides adequate support by increasing the temperature of the support material, the printable resin monomer system that is polymerized by a free radical reaction may begin to polymerize prematurely, which can cause problems such as clogging of the jetting tip. Summary of the Invention

[0004] The scope of protection sought for various embodiments of the invention is indicated by the independent claims. To the extent there are exemplary embodiments and features described herein that do not fall within the scope of the independent claims, they should be construed as examples useful for understanding various embodiments of the invention.

[0005] According to a first aspect, there is provided a method for manufacturing a printable object, the method comprising using a printing element having one or more print heads, each including a movable injection tip, to inject a printing material, which may be environmentally friendly, into a support material, the support material being a complex fluid semi-solid gel-consistency material, wherein the injection tip moves horizontally in an xz direction within the material to form a cavern-shaped path for the printing material. It should be noted, however, that the injection tip can also be configured to move vertically.

[0006] In an exemplary embodiment according to the first aspect, the support material has a complex fluid, semi-solid gel consistency for supporting the printable material at temperatures and pressures suitable for the printable material.

[0007] In an exemplary embodiment according to the first aspect, the cavity has a width the diameter of the moving ejection tip, and the formed cavity is filled with injected printing material when the ejection tip moves, for example, horizontally.

[0008] In an exemplary embodiment according to the first aspect, movement of the ejection tip results in a local thixotropic decrease in viscosity at the walls of the cavity, the cavity is closed by a flow of support material, and the printing material is covered with support material that protects the printing material from the ambient environment but may promote polymerization.

[0009] In an exemplary embodiment according to the first aspect, the support material after flowing over the printed material protects the printed material from the polymerization inhibiting effects of oxygen, such that the printed object has a fully polymerized and glossy surface after being printed and polymerized in the support material.

[0010] In an exemplary embodiment according to the first aspect, the support material has a low Poisson's ratio, and the volume change of the support material due to the ejection tip and the volume of the ejected material occurs in a vertical direction towards the surrounding air.

[0011] In exemplary embodiments according to the first aspect, the configuration (or composition) and gel consistency of the support material reduces turbulent fluid flow when the ejection tip moves within the support material.

[0012] In an exemplary embodiment according to the first aspect, the force transmitted to the injection tip by movement of the injection tip exceeds the yield shear strength of the support material, so that the support material does not deform the injection tip.

[0013] In exemplary embodiments according to the first aspect, the support material comprises molecules, solids, emulsion additives, or bubbles that promote Mie and Rayleigh scattering when light is directed at the support material. Scattering disperses the light, reducing the light irradiation intensity reaching the head of the jetting tip and preventing clogging of the jetting tip when the injected material is photopolymerizable.

[0014] In an exemplary embodiment according to the first aspect, the support material has a gel consistency that retains evenly distributed protective gases for polymerization of the injection material, thereby preventing the gases from escaping from the material into the surrounding atmosphere.

[0015] In an exemplary embodiment according to the first aspect, the support material has a gel consistency that retains diffused oxygen or oxygen bubbles that are evenly distributed throughout the support material, providing oxygen to living cells throughout the support material.

[0016] In exemplary embodiments according to the first aspect, the printable material can be invaded by cells or compounds from the support material if the support material serves a second role as a reservoir for cell culture medium or a substance (or substrate) to be incorporated into the printable object. [Brief explanation of the drawings]

[0017] [Figure 1] Figure 1 shows the injection of printing material into the support material and the formation of a cavity for the printing material as the print head moves horizontally, and also shows the closure of the cavity by the flow of support material from the wall covering the printing material with support material. [Figure 2] FIG. 2 shows the time it takes for the cavities in the support material to close (closure time) when the amount of sucrose (or sugar) in the support material is changed. [Figure 3] FIG. 3 shows the amount of clogged material in the jetting tip when the support material contains varying amounts of sucrose. [Figure 4] FIG. 4 shows printing of molten thermoplastic printing material that solidifies in a support material. [Figure 5] Figure 5 shows the printing of a hollow object, where components of the support material are encapsulated. [Figure 6] FIG. 6 shows a variation of the printing system / method embodiment shown in FIG.

[0018] [Detailed explanation] The following embodiments are illustrative. Although this specification may refer to "an," "one," or "some" embodiments in several places throughout the text, this does not necessarily mean that each reference refers to the same embodiment or that a particular feature applies to only one embodiment. Features of different embodiments may be combined to form other embodiments.

[0019] One group of materials employed in additive manufacturing (AM) that have good physical properties and can be used for 3D printing are resin-based materials, resin-based composites, and hydrogels. These materials can also be processed by several AM techniques. However, current AM techniques have some limitations when manufacturing objects with complex shapes and objects that require good biocompatibility and surface quality. In bioprinting, a material commonly applied as a bioink is hydrogel. Hydrogels or other gel-like materials can also be considered as support bath materials (hereinafter referred to as support materials).

[0020] In the gelation of hydrogels, also known as aquagels, water is trapped within a network of material forming a gel. Gels are generally complex fluids characterized by binary mixtures with the coexistence of two or more states of matter: solid-liquid, liquid-gas, and liquid-liquid. Additives can alter the gel network formation and cause trapped liquid to escape from the spaces between the gelling agents. This can result in syneresis and increased gel viscosity. Gels also exhibit thixotropy, meaning that they become fluid when physically stressed by shaking or otherwise mixing, but become solid again when left at rest.

[0021] Hydrogels, also known as aquagels, are crosslinked hydrophilic polymer systems that are insoluble in water. During hydrogel gelation, water is trapped within the gel-forming material network, and intermolecular associations exist along the polymer chains. Hydrogels possess physicochemical properties that make them suitable for a wide range of biomedical applications. Their highly viscous nature, similar to that of natural soft tissue, allows them to be used as biomaterials in soft tissue augmentation. Furthermore, hydrogels can incorporate bioactive substances and cells, allowing them to be used as printable materials known as bioinks in additive manufacturing. The consistency and viscosity of hydrogels can be controlled by temperature. In some hydrogels, increasing temperature increases viscosity, while in others, the opposite is true. Hydrogels have low mechanical strength, which may make them unsuitable for use as load-bearing implants. However, they can be crosslinked to maintain their shape.

[0022] Several 3D printing techniques, devices, and resins are available for fabricating tissue engineering scaffolds, implants, implantable or orally administered drug-releasing devices, dental structures, and even living cell constructs. 3D printing can also be used to fabricate tumor cell-infiltrated scaffolds used in anticancer drug development and testing. One example of biostable device fabrication is the use of thermosetting monomer systems in implants and dental restorations. The printed materials are monofunctional or polyfunctional acrylate or methacrylate monomer systems, or filled resin composites. Alternatively, biodegradable resin-based materials can be selected for tissue engineering scaffolds and drug-releasing structures. Monomers cure via radical polymerization, cationic polymerization, cationic photopolymerization, or frontal polymerization, which are reactions inhibited by oxygen, e.g., ambient oxygen. To achieve complete cure, i.e., the degree of cure (DC), referred to as the monomer conversion of the monomer from the interior to the surface, oxygen should not be present during the curing process. The adverse effects of ambient oxygen can be prevented, for example, by using an oxygen protection barrier before final curing of the object. One oxygen protection barrier in AM technology is the support material, which can contain diffused or bubbly polymerization protective gas. Ideally, the protective gas should be evenly distributed throughout the support material and retained within the support material for the duration of the printing process. This can be achieved by adjusting the consistency and viscosity of the support material to prevent the gas from escaping the material too quickly. By too fast, we mean the duration of the printing process, for example, from a few seconds to several days.

[0023] A key issue in all 3D printing processes is first securing the printable material to a support and then supporting the print object while printing the material layer by layer. In the production of 3D printed objects with diverse geometries, in some instances, significant overhangs cannot be balanced by the printable object's body, resulting in the print material collapsing under gravity. One attempt to overcome this problem is multichannel plotting, which uses a temporary support material along with the main print material. This system is called a polyjet printing system. In one example, polyjet 3D printing allows a separate support material to be printed simultaneously with the print material. The support material then becomes an integral part of the printable object and must be removed later. After removing the polyjet support material, the printed object has a sticky, polymerization-inhibited, non-glossy, and non-biocompatible surface due to the printing process occurring in ambient air.

[0024] An alternative printing method involves injecting materials into a non-solid support material. The support material can be a fluid, complex fluid, colloid, gel, or semi-solid material. Systems using this method can be used, for example, to deposit and crosslink bioinks—a mixture of cells, a support matrix, and nutrients—to create tissue-like constructs. For example, bioinks can be printed onto poloxamer gels, a biocompatible poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer (PEO-PPO-PEO) gel that supports the printing bioink. However, when poloxamer gels and other gels are used as support materials for 3D printing with thermosetting monomers or composites using robocasting techniques, the gel can contaminate the surface of the printed layer, causing the printed layers to fail to adhere to each other via polymerization and resulting in weak structures in the printable object. Furthermore, movement of the printing tip through the support gel can cause turbulence and unsteady vortices, resulting in poor accuracy in the printed object formed from the printing material. Additionally, the fluid dynamics within the supporting liquid can cause movement of the supporting material itself, which deforms the printed object through elongation.

[0025] It would therefore be beneficial to have a system and / or method that can be at least partially controlled using a computing device (or computing equipment) for producing printable objects having planned shapes and dimensions by printing materials with extrusion injection techniques. It is desirable to print materials onto a support material that has a consistency and viscosity at room temperature and pressure (RTP), physiological temperature, or a temperature appropriate for the printing material being processed, and that allows the jetting tip of the printing device to move freely and support the printing material against gravity and lateral spreading, eliminating the effects of oxygen inhibition of free radical polymerization on the surface of the printing material.

[0026] In an exemplary embodiment of the desired support material system, the support gel-consistency material allows the tip of the printing tip to form a cavity in the support material as the tip of the printing tip moves horizontally. The force required to form the cavity needs to be small so as not to deform the tip of the jetting head. Thus, the shear stress to cut through the support material and form the cavity needs to be less than the stress that deforms the jetting tip.

[0027] FIG. 1 illustrates an exemplary embodiment of a system configured to implement a method for manufacturing printable objects using 3D printing. In this exemplary embodiment, the system includes a printing device, which may include a computing device or may be connected to a computing device that executes computer instructions such that printing of the printable object is controlled, at least in part, by the computing device. Furthermore, the printing apparatus includes one or more print heads, each print head including a jetting tip. One jetting tip is shown in FIG. 1 . In this exemplary embodiment, the system includes a printing device jetting tip 120 in the shape of a conical cylinder, which moves horizontally in the direction of the arrow and is used to cut cavities in a support material 115 into which a printing material 110 is injected. This is illustrated in scenario 100 in FIG. 1 . 1 also shows, in scenario 105, the backdrop of the horizontally moving jetting tip after a time period of approximately 0.5-60 seconds, where support material 115 flows out from the walls of the cavity (side arrows), covering the printable material 110 and protecting it from the inhibiting effects of oxygen in the ambient air. The cavity is gradually filled completely (vertical arrows) due to the thixotropy of the support material caused locally by the moving jetting tip.

[0028] The printing material 110 may be a biodegradable or biostable resin or resin composite of one of several functional reactive groups comprising a polymerizable monomer or comonomer system with compounds that allow addition or condensation polymerization: free radical polymerization, ionic polymerization, ring-opening polymerization, or head-on polymerization of the resin or resin composite. After polymerization, the resin may be any type of thermoplastic, thermoset, copolymer, blend, or interpenetrating polymer network (IPN). The printing material may also be a crosslinkable hydrogel or elastomer. It should be noted that the printing material may further comprise additional substances or materials.

[0029] The support material 115, in this exemplary embodiment, is a complex fluid-gel-consistency liquid that supports the printing material 110 against gravity and lateral spreading, protects the polymerization of the printable material from oxygen inhibition, keeps intentionally applied gases (protective gas for free-radical polymerization of printable resins or oxygen for live cells in printable bio-inks) evenly distributed in the support material during printing, and, in the case of light-induced polymerization, scatters the polymerization light and prevents it from being focused directly in the area of ​​the jetting tip, reducing the risk of jetting tip clogging.

[0030] The support material 115, in this exemplary embodiment, is ethyl or methyl cellulose (MC) (C6H7O2(OH)) at a concentration of 0.5 to 50.0 wt %, preferably 5 wt %, in water. x (OCH3) yMC is a type of gel-consistent material, such as MC or carboxymethylcellulose hydrogels. MC is a biocompatible homopolymer composed of glucose units linked by β-1,4 bonds. The methyl substitution of 1.6–1.8 makes it water-soluble at room temperature. Therefore, MC is water-soluble and is also used as a binder or thickener for pharmaceutical and food applications. MC is a cellulose ester, such as hydroxypropylmethylcellulose, hydroxyethylcellulose, and carboxymethylcellulose. Due to its viscosity characteristics and biocompatibility (FDA Inactive Ingredients Search for Approved Drugs), MC hydrogels are used as bioinks in extrusion-based printing. When heated, MC gels in water and exhibits thermoreversible properties. However, MC hydrogels are not gels at RTP or physiological temperature (37 °C), a property that is desirable for bioprinting and 3D printing of free-radical polymerizable resins and resin composites, or thermoplastics that need to be cooled and solidified by a low-temperature support material gel.

[0031] In RTP, MC-hydrogels lack gel viscosity, limiting their ability to support the printing material 110 against gravity and lateral spreading. Turbulent flow due to the forces generated by the jetting tip 125 movement can lead to dimensional errors (or dimensional inaccuracies) in the printable object. To avoid these problems, the consistency of a support material 115 such as an MC-hydrogel can be adjusted by adding molecular or colloidal particle systems. Suitable consistency adjusters include disaccharides of glucose and fructose (sucrose) or difructose anhydride (caramel), lactose, maltose, galactose, or liquid sugar, which, at concentrations between 0.5 and 99%, change the consistency of the hydrogel to a more jelly-like consistency while allowing the jetting tip 125 to move through the material and apply shear forces to cut cavities into the material.

[0032] When sugars are added to MC hydrogels at RTP, the polymer chains of the MC interact with each other, supporting the formation of intermolecular associations between the methyl groups of the polymer chains and the alkyl groups of the MC. This intermolecular association occurs spontaneously at temperatures above 42.5°C. Figure 2 shows the intermolecular associations 200 of MC with a degree of methyl substitution (DS) of 1.7-2.0. This intermolecular association makes the MC water-soluble and allows the polymer chains to form highly viscous gels at RTP. Gelation of MC in water at RTP occurs when sucrose dissolves in water and the MC hydrogel is mixed with water simultaneously. The hydroxymethyl groups 210 of the dissolved sucrose form weak chemical interactions with the methyl groups 220 of the MC polymer, and water molecules 230 are trapped in the intermolecular structure of the MC polymer chains 240. The resulting environmentally and biocompatible MC-sucrose hydrogels have gel viscosities suitable for applications requiring such viscosities at room temperature or physiological temperatures.

[0033] In the application of support materials for 3D printing, cavities should be closed to protect the printable material from the effects of ambient gases, such as air. In MC-hydrogel, the appropriate amount of sucrose to obtain the aforementioned properties is 80 wt%. Figure 3 shows a graph 300 of the effect of increasing the sucrose content of MC-hydrogel on the time of spontaneous cavity closure in RTP. An 80 wt% sucrose content in MC-hydrogel supports the printed material of the dimethacrylate resin composite against gravity and lateral spreading.

[0034] A sucrose disaccharide molecule (C) with a diameter of approximately 20 angstroms (2 nm) 12 H 22 O 11) crystallizes to a certain extent in the MC-hydrogel, reaching the size of colloidal particles, where the sucrose nanoparticles, especially at low temperatures, begin to scatter light (Tyndall effect), which is used to photopolymerize and crosslink printable materials with a typical light wavelength of 465 nm. Light scattering prevents direct light from concentrating in the area of ​​the ejection tip, reducing the local light intensity and power, thus preventing clogging of the ejection tip during photopolymerization of the injected material. Therefore, printing systems such as those described above can take advantage of light scattering. Figure 4 shows a graph 400 of the amount of printed material of a particle-filled resin composite, measured with a 465 nm LED curing light device irradiated (approximately 900 mW / mm) from a distance of 30 mm in an Erlenmeyer flask. 2 ) toward the ejection tip, the amount of printing material that can be injected into the MC-hydrogel before clogging occurs is shown for both the presence and absence of 80 wt% sucrose. Furthermore, if the MC-hydrogel containing sucrose, which is the support material in this example, contains tiny bubbles of a protective gas such as nitrogen or argon, light scattering is enhanced.

[0035] The MC hydrogel support material, with sucrose as a viscosity modifier at low temperature (RTP), allows for the printing of a molten thermoplastic polymer onto the support material. Figure 5 shows a modification of the printing system described in the exemplary embodiment of Figure 1. In this exemplary embodiment, there is a print material 510 and a support material 515, both of which are temperature-controlled in this exemplary embodiment. The print material 510 has a direction 535 and is a thermoplastic, heated print material that solidifies at the low temperature of the support material. In this exemplary embodiment, there is also a thermoelement 540 that keeps the support material cold and the sucrose to provide a jelly consistency. In this exemplary embodiment, the print material 510, which is polycaprolactone (PCL), is melted at a temperature of 60°C within the jetting tip and then injected by the system into the support material 515, which has a jelly-like viscosity at a temperature of 20°C. When the molten printing material 510 reaches the cooler support material 515, solidification occurs and the printed object assumes the intended shape and size. The direction of jetting tip movement is indicated by arrow 525, and support by the support material 515 is indicated using arrow 545.

[0036] MC hydrogels with sucrose additives and physiological oxygen (O2) partial pressure can be used as tissue engineering media. The oxygen partial pressure (headspace O2) level is approximately 18%. Figure 6 shows another variation of the printing system / method of the exemplary embodiment shown in Figure 1. In this exemplary embodiment, the support material 615 is an MC-sucrose support material, which acts as a cell and tissue culture medium composed of components including sucrose 654 and O2 656 for cell health. The support material 615 may also contain pharmaceutical or other biologically active compounds 652. When printing hollow structures such as balls or closed cylinders, the ejection tip 620 ejects the printing material 610 in a direction 635, trapping the support material 615 containing cells and components within the printable object. If the printable material is biodegradable or resorbable, the printable object, which can be implantable or drug-releasing, releases cells and active compounds at a targeted target area, for example, to initiate healing of a tissue defect or disease.

[0037] MC hydrogels can also be used as reservoirs for live cells used in drug discovery to test the effects of drugs on cancer cell invasion. At a temperature of 37°C, MC support materials containing cells, such as cancer cells, and sucrose as a viscosity modifier are used to print objects of predetermined size and shape on Matrigel or myomagel (Myogel) printable materials. In the absence of an effective drug against cancer cells, the cells invade, proliferate, and migrate through the support material into the Matrigel or Myogel printed object. Conversely, if the drug is effective against cancer cells, cell invasion into the printed Matrigel or Myogel object is inhibited. Cell invasion into the printed object, indicating the efficacy of the drug, is investigated by microscopic, colorimetric, or immunological means from the printable object. The precise shape and volume of the printable object, due to the jelly-like consistency of the support material, are necessary to calculate the degree of cell invasion.

[0038] In addition, the viscosity of hydrogels other than MH can be adjusted by adding sucrose molecules or some other molecules. Nonionic polyacrylamide (PAM) ((C3H5NO) n Biodegradable hydrogels include polyacrylamide gels (PAHs), cellulose microfibrils, cellulose nanocrystals, potassium salts, chitosan, alginate, polyvinyl alcohol, starch, and gelatin. These hydrogels can be tailored to the consistency required for 3D printing support materials or bioink applications. Biodegradable hydrogels are either naturally derived hydrogels such as polysaccharides (e.g., chitosan) and proteins (e.g., collagen), or synthetic hydrogels such as polylactic acid (PLA), polyglycolic acid (PGA), and polypropylene fumarate (PPF).

[0039] Due to its environmental properties, MC-sucrose-hydrogel can be used as a support or printable material for 3D printing in any technological field, and due to its biocompatibility, it can be used in any field of biotechnology and pharmaceutical development and manufacturing, as well as in food ingredients and food production.

[0040] Although the present invention has been described with reference to examples based on the accompanying drawings, it is clear that the present invention is not limited thereto and can be modified in several ways within the technical scope of the appended claims. Therefore, all terms and expressions should be interpreted broadly and are intended to illustrate, not limit, the embodiments. It will be obvious to those skilled in the art that, as technology advances, the concept of the present invention can be implemented in various ways. Furthermore, it will be obvious to those skilled in the art that the described embodiments may, but need not, be combined with other embodiments in various ways.

Claims

1. 1. A method for printing a 3D printable object, the method comprising: moving an ejection tip of a printing element included in the printing device at least horizontally within the support material such that the ejection tip forms a cavity in the support material, the support material being a complex fluid having a semi-solid gel consistency, the cavity corresponding to a shape of the 3D printable object; Injecting a printing material into the cavity with an ejection tip, the printing material comprising a biodegradable or biostable resin or an injection resin composite; and Covering the printing material with a flow of support material after the ejection tip has moved A method comprising:

2. The method of claim 1 , wherein the movement of the injection tip causes a local thixotropic decrease in viscosity at the wall of the cavity.

3. 3. The method of claim 1 or 2, wherein the force transmitted to the injection tip by movement of the injection tip exceeds the yield shear strength of the support material.

4. 4. The method according to claim 1, wherein the support material has a gel consistency that keeps the protective gas of the polymerization of the injection material evenly distributed on the support material.

5. 5. The method of any one of claims 1 to 4, wherein the support material has a gel consistency that retains diffused oxygen or oxygen bubbles evenly distributed in the support material.

6. The method according to any one of claims 1 to 5, the support material comprises molecules, solids, emulsion additives or gas bubbles that promote Miller-Rayleigh type light scattering; The method further comprises applying photopolymerization of the printing material.

7. The method according to any one of claims 1 to 6, The support material is a methylcellulose hydrogel with added sucrose; the support material is a gel at room temperature and pressure, or physiological temperature; The method further includes melting the printing material at the ejection tip before injecting it into the cavity.

8. The method of claim 7 , further comprising maintaining the temperature of the support material at a temperature lower than the temperature of the print material.

9. 1. A system including a printing device, the printing device comprises at least one print head including an ejection tip; A system configured to perform the method according to any one of claims 1 to 8.

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