CN110239087B - 3D printing apparatus based on imaging principle - Google Patents
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B29C64/10—Processes of additive manufacturing
- B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
- B29C64/124—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified
- B29C64/129—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified characterised by the energy source therefor, e.g. by global irradiation combined with a mask
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
- B29C64/264—Arrangements for irradiation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
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Abstract
The invention provides a 3D printing device based on an imaging principle, which comprises an optical path conversion unit, wherein the optical path conversion unit can project one or more images generated by a projection device into a curing unit for curing, and in some preferred modes, the curing unit is fixed and the optical conversion unit is arranged around the curing unit in a circular motion mode. Thus, a complex structure can be printed, and the precision of the printed structure is improved.
Description
Technical Field
The present invention relates to an optical 3D bio-printing system and also to a biological material for printing.
Background
Clinically, there are a large number of patients who cannot live a normal life because of necrosis of tissues and organs. The current primary treatment modality relies on autologous tissue transplantation or allogeneic organ donation. But the donation of the foreign body tissues and organs is far from meeting the actual clinical requirement. Moreover, transplantation of foreign tissues or organs also presents the risk of rejection, resulting in graft failure. Therefore, there are still a large number of patients who are not treated or who are not effectively treated.
In recent years, with the development of tissue engineering and regenerative medicine, the in vitro construction of tissues and organs with biological activity has become a hot research topic. However, the conventional tissue engineering means can only construct tissue engineering tissue with a simple structure, and there is no way to simulate tissues and organs in vivo from outside. The 3D printing technology is widely used in the field of tissue engineering and regenerative medicine as a more convenient and effective three-dimensional structure construction means.
Currently, the mainstream optical 3D printing methods mainly include Stereolithography (STL) printing and Digital Light Processing (DLP) based optical 3D methods.
DLP photocuring printing and extrusion printing. The DLP photocuring printing equipment comprises a liquid tank capable of containing resin and used for containing the resin which can be cured after being irradiated by ultraviolet light with specific wavelength, a DLP imaging system is arranged below the liquid tank, an imaging surface of the DLP imaging system is just positioned at the bottom of the liquid tank, and a thin layer of resin with certain thickness and shape can be cured each time through energy and graphic control (the cross section of the resin layer is completely the same as that of the resin layer obtained by cutting in the front). A lifting mechanism for lifting the tray is arranged above the liquid tank, the tray is stepped to form a thick forming surface between the tray (or a formed layer) and the liquid tank, and after each section exposure is finished, the tray is lifted upwards by a certain height (the height is consistent with the layering thickness), so that the solid resin which is cured at present is separated from the bottom surface of the liquid tank and is bonded on a lifting plate or a resin layer which is formed at the last time, and thus, a three-dimensional entity is generated by layer-by-layer exposure and lifting. The optical system of the DLP type 3D printer is fixed, and the optical system only completes printing one layer thickness at a time. Typically a first lifting and then lowering mode is used, i.e. if printing in a 0.1mm layer thickness, the first lifting is 5mm and then the lowering is 4.9 mm. The molding surface is on the liquid level every time, and the mold is immersed in the material liquid after molding. However, this method has a problem that the surface tension of the liquid affects the thickness of the molding layer and the molding effect. Moreover, the forming surface is on the liquid level every time, so the liquid tank needs to be filled every time of printing, even if the actual material consumption of the entity to be formed is far less than the volume of the liquid tank, the liquid tank needs to be filled, and the forming surface on the liquid level every time can be ensured; in addition, the remaining liquid cannot be reused after molding. In addition, DLP photocuring printing is carried mechanism and is also soaked in the feed liquid to in order to make the face of shaping at every turn at the liquid level, need balance to carry the volume difference that the mechanism of pulling sinks and lead to, therefore still need set up the balancing piece in the cistern, carry and pull mechanism, balancing piece and tray and all be located the cistern, carry and pull mechanism, balancing piece and occupy the sectional area of cistern, lead to effective shaping area (tray area) to be less than the sectional area of cistern, effective shaping area is little.
The existing preparation method of artificial soft tissue by extrusion and photocuring composite molding comprises the following steps: 1. modeling the artificial soft tissue to obtain an artificial soft tissue model; 2. processing the contour of each layer in the artificial soft tissue model: calculating the outline information of each layer in the artificial soft tissue model by using 3D printing layering software, and generating the outline information into a running path of the extrusion nozzle; 3. preparing a photocuring composite solution: mixing living cells, growth factors and a collagen solution to obtain a mixed solution, injecting photocuring hydrogel into the mixed solution, and then adding a visible light photoinitiator to obtain a hydrogel compound capable of keeping a certain shape; 4. taking the photocuring composite solution prepared in the step 3 as a raw material, and adopting a 3D printer to prepare the artificial soft tissue: 4-1, controlling a hydraulic extrusion head to extrude a hydrogel compound on a working platform according to a running path to form a semi-solidified gel layer; and 4-2, carrying out photocuring on the colloid layer to obtain a cured layer. The hydraulic extrusion head is fixedly connected with the light curing head, and when the hydraulic extrusion head is in a working state, the light curing head is closed; when the hydraulic extrusion head is reset according to the movement track during working, the hydraulic extrusion head is closed, and the light curing head is in a working state.
The disadvantages of this way of shaping biological tissue are: 1. in both the DLP method and the extrusion method, a plurality of materials cannot be used to cooperatively complete a biological tissue forming task, and thus, a mixed processing of a plurality of materials cannot be realized. The active organism is a heterogeneous mixed system containing various structures and various material components, and the method cannot complete the forming of the heterogeneous mixed system. 2. DLP's feeding, shaping is fast, but the extravagant feed liquid is many, and the one-time use rate of feed liquid is low. This also requires improved design over existing conventional printing, and it is desirable to be able to print more complex structures of bioactive materials.
However, human tissues and organs have complicated assembly structures and various compositions, and tissue or cell heterogeneity is an inherent property of living tissues. There is a need for an improved method for 3D printing of biological living tissue material or scaffolds to more closely approach the properties of natural living tissue, thereby providing more medical application value.
Disclosure of Invention
Therefore, to construct a bionic tissue and organ with physiological activity in vitro, the structure and components of a natural healthy tissue and organ need to be simulated simultaneously during 3D so as to realize the simulation of the physiological function in vitro, and thus, the living material with more application value can be provided.
The group of the invention can realize integrated printing of a complex structure based on the principle of integrated imaging, and can realize replacement of biological ink to simulate different components of tissues in the printing process by installing pipelines for feeding and discharging the biological ink at the upper end and the lower end of the resin tank. Therefore, it is completely feasible to develop an integrated color light 3D bio-printing system to construct bionic tissues and organs with physiological activities in vitro.
One of the purposes of the invention is to provide a 3D biological printing system which can realize integral forming and alternately supply a plurality of materials.
Accordingly, in a first aspect of the invention, there is provided a printing system comprising an optical imaging unit by which a printed subject is converted into an optical image. In some modes, the optical path conversion unit is further included; the unit allows the optical path of the image to be projected into the bio-ink which can be photo-cured, thereby allowing the image formed to photo-cure the bio-ink by focusing the light.
In some forms, a supply unit for supplying bio-ink, and a discharge unit for discharging bio-ink, the two units being connected directly or indirectly to the unit containing bio-ink for replacement of different bio-ink. The bio-ink, which is typically photo-cured, is contained in a curing unit. In some approaches, the curing unit may have bio-ink from a supply unit.
In some approaches, the image presented by the optical imaging unit comes from an image processing unit.
In some aspects, the image processing unit includes a computed tomography module that processes the three-dimensional image. In this case, after image processing, different digital image signals are formed and projected by a projection device, thereby exhibiting a layer in some partial or multi-layer structure of the subject to be printed.
In some embodiments, the image processed by the image processing unit is a three-dimensional modeled model, and slice images are rotated at regular angular intervals about a central axis. The model that the slice images collectively form here is a 3D printed structure that is either biomimetic or has the ability to carry biologically active cells.
In some preferred modes, the curing unit may be, for example, a quartz resin bath; the upper and lower outer sides of the curing unit are respectively communicated with the feeding unit and the discharging unit.
In other embodiments, the photo-crosslinkable bio-ink of the curing unit can be directly crosslinked by the image light, and the resin reservoir is independent of the optical system.
So-called independent, the position where the bio-ink is cured and the position where the optical imaging unit is relatively independent do not interfere with each other. Generally, the position (curing unit) where the bio-ink is cured is kept stationary, and the optical imaging system is in a changing state, which may be a position change, an optical imaging or a light wave change. In some modes, a light path conversion unit may be further included, and the unit performs position change with respect to the curing unit. At this time, neither the projection device nor the curing unit moves, but the conversion of transferring the projected image and projecting it to the curing unit is performed by means of a light converter. When a complex structure needs to be printed, an object is always a three-dimensional structure and is always a three-dimensional structure, which allows the angle and position of the optical path conversion unit to be adjusted, thereby performing the overall curing of different materials. The following detailed description is specific to particular embodiments.
This allows the bio-ink to be solidified and still, and thus, more precise and complicated structures can be formed, because when a plurality of bio-inks of different compositions are printed (solidified) continuously or simultaneously, the bio-inks are all fluid, such as liquid or semi-solid (non-solid), and the light solidification needs a certain time to complete, and if the solidification unit is moved, different bio-inks may be mixed during the solidification process, thereby causing cross contamination. When the light source is in a fixed position, the light source is changed, so that the position or the volume of curing can be accurately controlled, more precise printing is realized, and the light source has practical application significance particularly for the generation of a complex multi-dimensional structure.
The change or conversion of light can be embodied as a change in the location of the focused light, a change in intensity, to achieve different structures at different locations, or the printing or processing of more complex structures. Printing and processing herein are interchangeable and mean the same.
The curing unit can be a resin tank or a quartz tank, and aims to enable the optical system to project a real image in the central area of the quartz resin tank, so as to realize the photo-curing of the bio-ink. The material supply unit is arranged outside the optical system, the material liquid of the material supply unit is arranged outside the photocuring area of the optical system, and during printing, the photocuring of the biological ink can be carried out without moving the quartz resin tank. The optical system is spatially independent of the quartz resin bath, meaning that movement of the optical system does not result in movement of the quartz resin bath. In one form, the curing unit includes an inner container for receiving the bio-ink, wherein the inner container is stationary.
In some forms, the outer container includes a movable outer container on an exterior of the inner container, the outer container being rotatable about the inner container. In some forms, the rotation is a circumferential rotation. The outer container may be considered to rotate around the inner container. In the rotating process, the light is used for solidifying the biological ink at a fixed point, so that accurate printing can be realized
In a second aspect of the invention, a printing system is provided that includes an optical imaging unit that causes a printed subject to form one or more optical images that are projected into a print curing unit for photocuring.
In a preferred mode, the optical imaging unit comprises an image processing unit and a projection unit.
In a preferred mode, the image processing unit includes a module that performs a division process on an image of the printing subject.
In a preferred mode, the curing unit is connected with a plurality of discharge ports, and each discharge port of the plurality of discharge ports corresponds to different bio-ink, so that the bio-ink in the curing unit is removed.
In a preferred mode, the curing unit comprises a lifting platform, and the lifting platform can move upwards.
In a preferred mode, the image is projected from the bottom to the top through the curing unit.
In a preferred mode, the curing unit is located between the lifting platform and the projection device.
In a preferred form, the segmentation is a partial structure segmentation of the printed body, the segmented image being projected into a curing unit.
In a preferred mode, the system further comprises a feed inlet connected with the curing unit, and the feed inlet comprises a detachable bio-ink device which can bear a plurality of different bio-inks.
In a third aspect, the present invention provides a printing apparatus comprising an optical path conversion unit capable of projecting one or more images generated from a projection apparatus into a curing unit for curing.
Preferably, the curing unit comprises an ink reservoir for containing bio-ink, the image being projected into the ink reservoir.
Preferably, the light path conversion unit and the curing unit are arranged in a relative rotation manner.
Preferably, the curing unit is stationary, and the light path conversion unit is disposed in a circular motion manner around the curing unit.
Preferably, the light path conversion unit projects the projection image into the curing unit by reflection of light.
Preferably, wherein the reflected light is perpendicular to the curing unit.
Preferably, the longitudinal axis of the curing unit is perpendicular to the image axis of the projection device.
Preferably, the apparatus further comprises a case containing an ink container, the case surrounding the ink container, and a liquid having a refractive index close to that of the ink contained between the ink container and the case.
Preferably, the optical path conversion unit includes a lens and/or a mirror.
Preferably, the lens converts light from the projection device into parallel light, and the mirror projects the parallel light perpendicularly into the curing container.
Preferably, the optical path conversion unit is rotatably disposed relative to the curing unit.
Preferably, the optical path conversion unit includes a mirror.
Preferably, the apparatus further comprises a rotation angle measuring device for measuring the angle of rotation of the optical path conversion unit around the curing unit.
Preferably, the projection apparatus further comprises a computer system for adjusting the angle of the projected image by the angle measured by the angle measuring device.
In a fourth aspect of the present invention, the present invention provides an integrated colored light 3D bioprinting method based on imaging principle, the method comprising: providing a three-dimensional modeling graph of the printed subject; the image processing unit is used for dividing the three-dimensional graph to form image information, the projection device is used for converting the image information into one or more images, and the optical conversion unit is used for transferring the images to the curing unit to perform photocuring on the biological ink.
Preferably, the image processing unit is a file including a software Matlab to read the model.
Preferably, wherein the segmentation of the Image is performed on the 3D model using Image Processing Toolbox in the software Matlab.
Preferably, the model uses Image Blending Package in the software Matlab for Image fusion.
Preferably, a central symmetry axis of the model is found, a plane containing the symmetry axis is made, and data is output by mapping the 3D model on the plane; and rotating the plane in the clockwise direction, cutting once at certain same angle, and obtaining the processed result file data after the cutting process is circulated.
Preferably, the resulting file data is transformed by the projection device to obtain one or more images.
Preferably, wherein the optical conversion unit is caused to move in a circular motion around the curing unit.
Preferably, the optical conversion unit converts the vertical light into parallel light and makes the parallel light perpendicularly incident into the curing container.
Detailed Description
Image processing system
In some approaches, the image processing system is based on the basic principle of Computed Tomography (CT). First, a two-dimensional slice digital image of an object to be printed is obtained from a three-dimensional model thereof. Then, each slice image is projected at certain angle intervals along the direction of 360 degrees, and one-dimensional line integrals along all projection directions are obtained. The angle here may be any angle, for example, 1 degree, 2 degrees, 5 degrees, etc. In a certain projection direction, the line integrals of all the slice images are superposed along the slice cutting direction to obtain a two-dimensional projection image in the projection direction.
The smaller the angular interval of the projected image, the higher the resolution of the printed object. Theoretically, a higher resolution can be achieved with a projection interval of 1 °. In some approaches, the projection images are filtered to avoid "star artifacts" in the reconstructed object. Since the filtered projection inevitably introduces negative pixel values, in order to realize normal projection and obtain the highest possible printing resolution, the system designs and applies an iterative optimization algorithm so as to obtain the highest printing quality.
Image processing is the pre-processing of the three-dimensional modeling of printing, and it is desirable to segment the modeled subject into different fragmentary parts so that different complex structures can be accurately machined. As is well known, in these complex structures, the living body is not in a state of continuous mean but in a state of discontinuous non-mean, and only the subject of the processing is infinitely or precisely divided to form different divided units, and the texture and structure of the divided units are not completely the same, so that the processing can be performed with different bio-inks, and the processing can be performed for each divided unit, and the processing of the complex structure can be completed finally. The image segmentation may be either longitudinal or transverse, and then the three-dimensional image of the printed subject is divided into a plurality of image elements, each image representing a layer of the structure to be photocured, and finally the subject is a complete structure consisting of numerous images and, upon photocuring, numerous cured layers.
When the division is performed, the complex structure is actually analyzed or decomposed to form different image units, and the image units are subjected to layered curing processing. These image elements are based on optical images, which are typically realized by means of a projection device. After the image unit is projected into the bio-ink, the image unit is cured, and after the curing is completed, if the structure indicated by the next image unit is different from the structure indicated by the previous image, such as texture, density, whether a blank exists or not, different inks need to be replaced for curing, at this time, the ink of the previous image is removed, another corresponding different ink is added to cure the next image, and so on, so that the so-called color printing can be realized. If the higher the resolution of the image processing, the smaller the image unit, the tighter and finer the printing effect.
When the image is projected, the image is not directly projected into the curing unit, but the image is converted into the light path, so that the light of the image is converted into the light path, and the light is perpendicular to the curing unit, so that the light is cured. Generally, the intensity of light of one image is the same (when the printed areas corresponding to the images are made of the same material), the areas with light are cured, and the areas without light are not cured (for example, the corresponding printed areas are made of the same material, but have structures such as holes, etc.). The light used for curing is the light converted from the light path. It can be understood that the image processing is to continuously divide the three-dimensional model to form a plurality of different image units, each image unit represents a surface of the main body to be printed, the length or thickness of the surface can be freely set, and can be rectangular, circular or any shape, and the thickness can be different from several micrometers to several millimeters. If the composition of the print main pattern is a plurality of different structural compositions, the image processing is divided according to the different structures, thereby obtaining different divided image data.
For example, a specific image processing method will be described with reference to fig. 8, 9,10, and 11 as an example as follows:
1. the target printing structure is created by modeling with CAD software, and may be, for example, a columnar structure with upper and lower layers, such as the upper and lower side structures shown in FIG. 8, or a three-dimensionally constructed structure with different internal structures.
2. The upper and lower layers of the model are separated and exported to the format files of the upper layer structure (upper.stl) and the lower layer structure (bottom.stl), respectively, as shown in fig. 9 and 10.
3. The stl files of upper and bottom are read using the software Matlab.
4. The Image Processing Toolbox in the software Matlab was used to segment the images of both the upper and bottom 3D models (degree of segmentation was 0.9 °).
5. The two models of upper and bottom are image fused by using the ImageBlendingPackage in the software Matlab, and the holes are corresponding.
6. Finding out the central symmetry axes of the upper model and the bottom model, making a plane containing the symmetry axes, and outputting the mapping of the 3D model on the plane, wherein the output is a digital mode;
7. rotating the plane clockwise, cutting once every certain same angle, as shown in fig. 11, after the cutting process is completed in a circulating manner, obtaining a result file after the processing is completed, and outputting a digital pattern ().
Projection apparatus and optical path conversion unit
In some approaches, the core of the optical system is a DLP projector 1005 and/or stepper motor 1004. A DLP projector is a fixed device that is responsible for converting image processed information into an optical image (one or more images), where the image data is from an image of a three-dimensional model processed by an image processing system.
The outgoing light from the projector 1005 is projected through the optical path conversion system or conversion unit 1002 into the container containing the bio-ink, thereby rendering an image to be cured in the container. The image is the same as the generated optical image or processed image, the images are all represented by light, the light is converted through the light path, the emergent light is converted into the curing container, and therefore the light is focused and cured, and the cured shape and the image can be in one-to-one correspondence.
In some embodiments, the light emitted from the projector is converted into parallel light by the lens 1003 and then reflected by the mirror 10129,10128,10127 and directed into the container 1102 containing bio-ink. The optical path conversion unit may include a lens and/or a mirror here.
In some embodiments, where light is projected into the curing container, which may be disturbed, it is desirable that 100% of the reflected light is projected into the curing container without changing its direction, so that the size and quality of the projected image projected into the curing container is consistent with the projected image, and that the projected image is consistent with the actual segmented image. By uniform is meant size, location, and pixels, and the like. However, it is not easy to do this. This actually involves light interference and image distortion.
In one embodiment, the curing container is generally curved, for example circular, as the light path conversion unit moves around the curing unit or curing container, so that an image can be projected into the ink in the container over a 360 degree range. However, the container has a wall with a certain thickness, and the parallel light from the reflector 1002 is projected onto the wall of the cylindrical curing container, and it is desirable that the direction of the parallel light is not changed and enters the bio-ink. However, since the wall of the cylinder is not a mirror surface, refraction or reflection of light (a plane not perpendicular to the parallel light) occurs on the wall of the other curved surface, thereby causing distortion of the image and reduction in the intensity of light. Therefore, to reduce refraction, a polarizing element is provided around the curved wall, which corrects the direction of the light entering the container, making each light as perpendicular as possible to the curved wall, thereby reducing the light deviation. In one form, the polarising unit may be an original of a cube, and a liquid having a refractive index close to that of the bio-ink is filled between the cube and the curved wall, so that light entering the curing container is always vertical and does not affect the change in shape of the image. In some preferred embodiments, to reduce the refraction of the projected light by air entering the resin bath (or curing container 1102), the resin bath is placed 1101 in a box containing a liquid 1104 having a refractive index similar to that of the bio-ink, and the main light of the projector is always incident perpendicular to the surface of the box, so that the light entering the curing container is always kept perpendicular. The square box is located outside the curing unit and surrounds the curing unit, and may be a container of any shape matching the curing container in which the curing container is located. Bio-inks are generally liquid and, when light is present, can be cured by light to form a solid. The structure similar to the square box can be integrated with the light path conversion system, and when the light path conversion unit moves, the square box also moves around the curing unit together. This makes it possible to always keep the reflected light incident perpendicularly into the curing container. It can be understood that the square box and the curing unit can be kept in a fixed state in a unified structure, and the light path conversion unit can rotate relatively to project light into the curing container. The curing vessel may be any shape, and a rectangular parallelepiped, a cylindrical body, or the like may be used.
In other embodiments, the polarizing element may be a glass prism and/or a cylindrical lens. In some embodiments, a glass prism and a cylindrical lens are disposed around the curing container, wherein one surface of the glass prism is curved and conforms to the curved surface of the ink container, and the rest is flat. The joint with the ink container is filled with oil with the same refractive index as that of the prism and is used for light penetration and lubrication during rotation. The cylindrical lens is used to compensate for a shift of an image focal plane caused by a refractive index deviation between the glass prism and the ink. So that light enters the curing container and the image is kept consistent with the size of the projected image. For example, as shown in fig. 19 and 20, the curved container wall 6001, the glass prism 6002, and the cylindrical lens 6003 have a lubricant at the joint between the container wall 6001 and the glass prism 6002, which reduces the friction of the glass prism when rotating around the container, and keeps the direction of light entering the container as parallel as possible because the refractive index of the lubricant is the same as that of the prism. When parallel light passes through the cylindrical lens, enters the glass prism, passes through the oil, and then passes through the wall of the container, the light is still parallel in the container, so that the shape and position of the image formed in the container keep a precise position with other solidified images, thereby keeping the solidified structure in the container consistent with the actually designed modeled structure, or the printing precision is not enough, especially for complex and tiny structures, the precise printing is more required. This is to project the parallel light from the reflector into the ink in the curing container as much as possible, and to make the direction of the light not change; are all parallel light. For example, as shown in fig. 11, the image processing system is longitudinally cut along the central axis to form different rectangular bodies, which are actually longitudinal sections (for example, faces of a rectangular body) of a cylinder, and the images are input to the projection apparatus after passing through the image processing system, and then projected by the projection apparatus to form a rectangular face in a container containing ink by projection and reflection of light, while at the place where the light is irradiated, the light passes through the ink, and is focused on the formed rectangular body face to cure the ink, thereby forming a cured rectangular body face. When the next surface needs to be printed, the projector continues to project the next image, then passes through the optical path turning system, and generates another graph in the container filled with ink, and the focusing position is changed, so that the optical path needs to be rotated, and the light is focused on another plane, so that the ink is solidified.
When in fact a projected image is not a complete plane but a locally notched plane where there is a hole (e.g., the 106 cut plane of fig. 9), the projection is a projected notched image, where there is no focus of light, so that no curing occurs. Thus, a complete three-dimensional structure is printed in the bio-ink through continuous circulation.
In the printing process, the stepping motor 1004 drives the light path conversion unit 1002 to make a circular motion around the curing unit. In some embodiments, the mirror and the cube are rotated synchronously, and the projector and the resin tank are stationary, or the lens is stationary. The centers of rotation of the mirror and the cube coincide with the geometric center of the curing unit, e.g., the resin bath. And according to the preset angle interval of the image processing system, the stepping motor drives the reflector and the square box to rotate by an angle in the same direction every time the stepping motor rotates by an angle, and meanwhile, the projector quickly switches to the next projection image to complete exposure in one projection direction. After 360-degree exposure, specific exposure distribution is formed in the resin tank, the positions exceeding the photocuring exposure threshold of the biological ink are solidified and formed, and the rest positions are still liquid, so that 3D printing of the model is realized.
Therefore, how to determine the image division is determined according to different image division modes through light conversion or rotation. In some embodiments, the division may be performed tangentially to form different image elements. The division of fig. 8-11, for example, is in the form of a circle. For example, the upper layer of cylinders and the lower layer of cylinders are of different texture, but the upper layer structure itself is of the same texture except for the holes, so that one ink is sufficient. However, if the superstructure itself has other different properties, such as different sizes, different locations, or different textures of the apertures, the image processing needs to continue with the decomposition, knowing that the decomposition into different image elements is to be done for single image-by-one curing printing.
The optical system will be described with reference to fig. 13 by printing the two-layer structure shown in fig. 8.
1. And importing the file processed by the image processing system into the optical system.
2. The DLP projector is turned on to produce a different projected optical image, typically one image after the other.
3. The GelMA feeding unit 1 is used for feeding bio-ink GelMA from the lower part of the inner layer container, and the height of the bio-ink is slightly larger than that of the lower layer structure.
4. Starting a printing program, the projected image of the DLP projector is projected to a container loaded with bio-ink through the optical path turning system, wherein the inner container 1102 is loaded with bio-ink and is fixed, and the outer container (square box 1101) rotates along with the rotating platform. Model cutting images of DLP projection at different angles can be subjected to corresponding angle transformation by means of a light path turning system to realize 3D printing of the model. The realization method is that the stepping motor drives the light path turning system to rotate through the transmission device, so that the projection image can be projected randomly along the direction of 360 degrees. (PC program control stepping motor rotation and projector image synchronous switching)
5. After the light path turning system rotates 360 degrees, the biological ink GelMA in all the angle projection areas is solidified and formed, and the rest positions are still liquid, so that the printing of the lower layer structure is completed.
6. The discharging unit completely pumps out the uncured biological ink GelMA from the bottom of the inner-layer container. Then a supply unit 2 filled with SilMA injects bio-ink SilMA into the resin tank from the lower part of the inner container, and the height of the bio-ink is slightly larger than the height of the top surface of the upper layer structure corresponding to the resin tank.
7. And (5) repeating the steps 4 and 5 to finish printing the whole model of the figure 8.
FIG. 12 is a microscopic structure of each layer, in which top views of different cavity sizes can be seen, and side holes and top-view holes are arranged identically to each other. Meanwhile, a fluorescence structure diagram of 400um is observed under a fluorescence microscope. This allows more elaborate printing of complex structures.
In some modes, the light path conversion unit can do circular motion around the curing unit or relative up-and-down motion; or the alternating of the circular movement and the up-and-down movement can be freely arranged. These setting modes are decided according to the main body of printing. If different locations inside the printed body have different structures, e.g. the same printed body, e.g. like the structure of fig. 9, the structure is loose at the lower side close to the lower face 102 and tight at the upper side, or the whole structure gradually transitions from loose to tight at the lower and upper side, except for having a hollow. When printing such a structure, in the case of three-dimensional image processing, the image is divided in the transverse direction, the loose structure and the fine structure are divided in the transverse direction, and then the material having the same texture is divided in the longitudinal direction. When the texture structure is in a transitional state, but when images are divided, the dividing precision needs to be high, the texture in each image is basically the same, but the images may be different, and when printing is carried out, ink needs to be replaced for many times, and the light projection angle needs to be adjusted for many times. For example, when the first image represents a loose underlying textured material, the pattern of the loose underlying material is cured, but the second image represents a tight texture print, the loose and fine texture images lying in the same longitudinal split plane, and at this point the ink representing the tight texture can be replaced, and the light conversion system moved upward to cure the tight textured surface of the print on the loose surface. There may be no circumferential movement at this time, but up and down movement. If the image elements are close-packed or loose-packed in succession from the lower layer to the upper layer, the transverse and longitudinal division can be performed, and each image element finally divided represents a print-cured element which can be large or small in area, even a few micrometers, a few millimeters or centimeters, etc., so that only one light beam is required for the so-called image element during photocuring.
In summary, the image size and segmentation are performed by the image processing unit, and the projection device reflects the image of the image segmentation, and the optical path conversion is performed to print the solidified layer with the size consistent with the image or with the scaling up or scaling down.
Rotation angle detection device
In other embodiments, the system further comprises a rotation angle detection device, which is connected to the computer system and is used to monitor and control the rotation angle, or alternatively, to correct the image. In the present invention, the relative positions of the mirrors are generally fixed and different, and these mirrors are moved circumferentially around the curing container, i.e. are moved circumferentially around the curing container. After the image transmitted from the projection device passes through the lens, the direction of the light rays is changed, and at least the light rays are changed into light in the vertical direction, such as parallel light, the light in the vertical direction is transmitted for multiple times through the reflecting mirror, and the direction of the light rays is changed into the parallel light which enters the curing container to form the image. However, when the rotation is required and the next image is to be printed, no matter what angle the rotation is, the angle of the projection mirror and the reflection mirror in the horizontal direction changes, so that the direction of the light emitted from the projection mirror and impinging on the reflection mirror 10129 changes (compared with the previous image), although the light is reflected for 2 times or for multiple times, the image itself changes in angle in this case, the shape of the image may not change, but the angle of the image changes, so that the angle of the image projected into the curing container changes, and an error occurs in the printed material. In this time, the rotation angle tester monitors the horizontal rotation angle of the reflector in real time, and after the actual angle is input into the computer control system, the computer calculates the actual angle to compensate the projected angle in advance, so that the angle is not changed after the light of the projected image passes through the lens and is reflected.
For example, in fig. 18, when the projected first image is 0 degree, the projected first image is projected at an angle of 0 degree after the optical path is converted by the lens and the reflection, but when the mirror is horizontally shifted by a certain angle (for example, 45 degrees), if the projection apparatus still transmits the second image of 0 degree, as explained above, the second image projected to the curing container is also at an angle of 45 degrees, which is deviated from the first image of 0 degree, and thus is not in accordance with the image actually required to be printed. In order to reduce such errors, the angle of rotation is measured by a rotation angle detection device and then input to a computer system which is operated to advance the projected grazing image by an angle of 45 degrees and then, after conversion of the optical path, to project the projected image into the curing container at an angle of 0 degrees so that the angles of the two images are coincident. It will be appreciated here that when the angles of the two images to be printed are identical, a change in the angular position of the projected image is required, this change being due to the adjustment made by the change in the angles of rotation of the projection and mirror. If a certain angle is required between the images which are originally desired to be printed, the angle of the projected image is still required to be adjusted to be consistent with the angle between the designed images by monitoring the rotating angle through a rotating angle detection device.
Similarly, when the image is rotated by 90 degrees, the projected image also needs to be adjusted to be rotated by 90 degrees in advance through calculation, and as can be seen from fig. 18, the image of 0 degree and the image of 90 degrees have the same size, but different directions and different angles, so that the angles of the images projected to the curing container are all 0 degrees.
The method of adjustment here is to filter the projection image. The introduction of negative gray pixels in the filtered projected image is inevitable. The program uses a gray threshold constrained optimization algorithm to eliminate negative gray pixels to obtain an optimized projected image that can be displayed by the projector. The optimization algorithm is shown in fig. 21. The exposure distribution threshold of the biological ink gelling is determined through experiments, the constraint gray level is determined according to the exposure threshold, the gray level is utilized to constrain the projection image, so that the correct exposure distribution in the final biological ink is ensured, namely, the exposure of the model is higher than the threshold for solidification, and the exposure of the rest positions is still liquid when being lower than the threshold.
The device drives the rotating platform to rotate through the stepping motor, so that a projection image of the projector can be projected onto biological ink in any direction through the light path turning device. The projected image of the projector is synchronously switched along with the rotation of the stepping motor. The stepping motor and the projector are controlled by a PC program. The control program is based on the Boost of C + + language, namely an Asio library, and the serial port communication protocol is an RS-232 communication protocol. During the rotation of the platform, the light path of the light path turning device determines that the projected image projected on the bio-ink rotates along with the rotation of the platform, and the rotating angle of the platform in unit time is equal to the rotating angle of the emergent image. Therefore, during programming, the projected image in each direction is read into the memory by rotating by a corresponding angle along the opposite direction of rotation and then is sent to the projector, so that the image projected on the biological ink is ensured not to rotate.
This, of course, has the advantage of ensuring the accuracy of the image, i.e. the accuracy in terms of the angle at which the image is printed. The reason is that the stepping motor drives the original structure 1002 where the reflector is located to rotate, which is the movement of a mechanical structure, mechanical errors are inevitably generated among all parts, when a precise structure is printed, one mechanical error exists every time the precise structure is rotated by one angle, when the cutting angle is 0.01 degrees, a three-dimensional structure has 36000 longitudinally cut images, each secondary image needs to be projected once and exposed once, 36000 times of rotation are needed, the mechanical error is larger, the more images are actually printed, the smaller the angle is, and the larger the generated mechanical error is. The angle change is monitored by adopting the rotation angle detection device, the change of the rotation angle can be accurately measured, and the angle of the image is adjusted according to the change, so that the change of the image angle caused by mechanical errors is overcome.
Feeding material
The feeding unit feeds into a curing container, such as a quartz resin tank, and the feeding amount is substantially equal to the amount of bio-ink corresponding to the highest height of the target structure at the stage of molding each time. By substantially equal, it is meant that the amount of feed is sufficient to provide the amount of bio-ink required for formation. In some embodiments, the number of feed units is greater than or equal to 2. Each feeding unit has its own independent charging barrel, and the feeding rods are connected with the quantitative driving mechanism, but have a common discharge port at the bottom of the quartz resin tank, and the feeding rods are connected with the quantitative driving mechanism. The feed rod pushes the biological ink in the charging barrel to flow out of the discharge port, and the biological ink flows into the quartz groove and reaches the target height. The discharge port is arranged at the bottom of the quartz resin tank, so that the mechanical impact of the biological ink on the formed structure during feeding can be avoided. The feed units are provided with a plurality of feed units and are used for providing bio-ink with different properties to realize the generation of non-homogenized bio-materials.
The feeding mode is controlled by a controller and a sensor, and the sensor and the controller control the feeding of the quantitative driving mechanism. Preferably, a certain feeding unit is designated for feeding, or a plurality of feeding units alternately realize the processes of feeding, photocuring, discharging, re-feeding and photocuring. For example, there are two units of the first feeding unit and the second feeding unit, the first feeding unit feeds and photocures, then the discharging unit discharges uncured bio-ink from the first feeding unit, and then the second feeding unit feeds and photocures, thereby realizing cross feeding of different units.
Or a plurality of feeding units feed materials simultaneously, and light curing is carried out after the feeding is finished. For example, there are two units of first feeding unit and second feeding unit, and first feeding unit and second feeding unit feed simultaneously, and the feed sum of all units satisfies the required feed liquid volume of current layer shaping, carries out the photocuring after the feed is accomplished.
Or the appointed feeding unit is adopted for feeding in one or more molding stages, the multiple units are adopted for feeding in one or more molding stages at the same time, and the multiple units are adopted for feeding in one or more molding stages alternately. Or, one of the feeding units is designated to feed, and the other units are suspended. In this way, a single material print is formed.
Quantitative driving mechanism
The quantitative driving mechanism is used for quantitatively pushing the feeding rod, and realizes control of a feeding mode by controlling the quantitative driving mechanism. In some preferred aspects, the dosing drive mechanism includes a feed drive member, and the feed drive member is coupled to the feed bar. Preferably, the feeding driving part comprises a clamp, and the feeding rod is clamped on the clamp and connected with the feeding driving part. When the clamp loosens the feeding rod, the feeding rod is separated from the feeding driving piece. The feeding driving part adopts a motor, a transmission mechanism (such as a screw rod mechanism), an electric push rod, a cylinder and the like.
Preferably, each cartridge has a respective cartridge holder to which the cartridge is secured. Preferably, the cartridge holder includes a fixing portion and a connection portion with the robot arm. The fixed part is fixed with the feed cylinder, guarantees the stability of the ejection of compact, and the change of feed cylinder is realized to arm connecting portion.
Discharging
In a multi-material print job, it is sometimes necessary to first drain the first bio-ink and then add the second bio-ink. In some preferred embodiments, the printing system has an outfeed unit. Preferably, the discharging unit comprises a discharging port positioned at the bottom edge of the quartz resin tank, a discharging pipeline connected with the discharging port and a negative pressure aspirator. After the first biological ink is printed, the discharging unit starts negative pressure suction to suck away the residual uncured biological ink. After the former biological ink is discharged, the second feeding unit works and the second biological ink is added, so that the mutual influence and interference of the two biological inks can be avoided.
Material and feed liquid:
in the present invention, a material or feed liquid refers to a material or mixture intended to be processed by a printer. When processed with the 3D printer of the present invention, some of the existing biomaterials can be used for printing. For example, many materials include natural polymers: collagen, silk fibers, gelatin, alginate and synthetic polymers: polyethylene glycol (PEG) or any combination thereof may be used in the printer of the present invention for processing. These are also referred to as "bio-inks" as materials for bio-3D printing. Although the material itself is conventional, it can be printed using well-defined printing. The printed biological material has a three-dimensional structure or a thought space, and any through hole can be arranged.
In some forms the cartridges are receptacles containing different materials and different cartridges may be used to hold the same material. Optionally, different materials or biological inks can be contained in the material cylinder, for example, the material cylinder A contains one biological material, the material cylinder B contains another biological material, the properties of the two materials are different, and the printing technology of the invention can realize the printing of complex biological tissues or organs. This is because a biological material or organ is not uniform in structure but has a difference in structural or biological properties. For example, mammalian skin materials, including epidermis, dermis, which has blood vessels and tissues connected to muscles, have different structures at different parts, different thicknesses, and different transition structures between the tissues, and such differences include density, pore size, and the like. Thus, if printing by conventional printing is required, all structures or tissues are the same, and by the printing technique of the present invention, biomaterials of different structures can be processed at once.
In some embodiments, the material of the present invention may be processed or printed in combination with stem cells, such that the material serves as a scaffold and the cells can be differentiated as an active agent, ultimately forming viable tissue. Of course, it is also possible to print the scaffold structure and then allow the stem cells to fill the space of the scaffold, eventually also forming living tissue.
In general, the newly designed printing of the present invention can print any suitable material.
In some embodiments, the present invention provides a new 3D printing bio-ink, also known as new materials. In some specific modes, the invention provides a light-controlled 3D printing biological ink or material, which comprises macromolecules modified by a light-responsive crosslinking group, macromolecules modified by an o-nitrobenzyl type photo trigger, and a photoinitiator. In some examples, water, such as deionized water, is also included. In some preferred modes, the mass final concentration of the macromolecule modified by the photoresponsive crosslinking group and the mass final concentration of the macromolecule modified by the o-nitrobenzyl type photo-trigger are both 0.1-10% of the mass of deionized water.
In some preferred modes, the mass final concentration of the photoinitiator is 0.001-1% of the mass of the deionized water.
In some preferred modes, the grafting substitution rate of the photoresponse crosslinking group in the macromolecule modified by the photoresponse crosslinking group is 10-90%, and the photoresponse crosslinking group is methacrylamide, methacrylic anhydride, glycidyl methacrylate or acryloyl chloride.
In some preferable modes, the graft substitution rate of the o-nitrobenzyl light trigger in the o-nitrobenzyl light trigger modified macromolecule is 1-100%.
In some preferred modes, the o-nitrobenzyl type photo-trigger modified macromolecule is shown as a formula (I), wherein R is1is-H or is selected from-CO (CH)2)xCH3、-CO(CH2CH2O)xCH3、-CO(CH2)x(CH2CH2O)yCH3Ester bonds of (2) selected from- (CH)2)xCH3、-(CH2CH2O)xCH3、-(CH2)x(CH2CH2O)yCH3、
Ether bond of (A) selected from-COO (CH)2)xCH3、-COO(CH2CH2O)xCH3、-COO(CH2)x(CH2CH2O)yCH3Carbonate bond of (2) selected from-CONH (CH)2)xCH3、-CONH(CH2CH2O)xCH3、-CONH(CH2)x(CH2CH2O)yCH3Wherein x and y are not less than 0 and are integers; r2is-H or is selected from-O (CH)2)xCH3、-O(CH2CH2O)xCH3、-O(CH2)x(CH2CH2O)yCH3Wherein x and y are integers not less than 0; r3Selected from amino linkages-O (CH)2)xCONH(CH2)yNH-, halogeno-type connecting bond-O (CH)2)x-and a linkage of the carboxyl type-O (CH)2)xCO-, wherein x and y are integers of not less than 1; r4is-H or-CONH (CH)2)xCH3Which isWherein x is not less than 0 and is an integer; p1Is a macromolecule;
further, the o-nitrobenzyl type optical trigger is preferably o-nitrobenzyl.
In some preferred modes, the natural biological macromolecule in the macromolecule modified by the photoresponsive crosslinking group and the macromolecule modified by the ortho-nitrobenzyl light trigger is one of glucan, hyaluronic acid, gelatin, sodium alginate, chondroitin sulfate, fibroin, chitosan, carboxymethyl cellulose or collagen, polyethylene glycol or citric acid Polymer (PEGMC).
In some preferred forms, the photoinitiator is one of 2-Hydroxy-4'- (2-hydroxyethoxy) -2-methylpropiophenone (2-Hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone, I2959) or phenyl (2,4, 6-trimethylbenzoyl) lithium phosphate (LAP); the mass ratio of the photoinitiator to the macromolecule grafted and modified by the photoresponsive crosslinking group is 1-3: 100.
In some preferred modes, the graft substitution rate of the macromolecule modified by the photoresponsive crosslinking group is 10-30%; the graft substitution rate of the macromolecules modified by the o-nitrobenzyl optical trigger is 1-20%.
In some preferred forms, the macromolecule modified by the photo-responsive crosslinking group is one of a methacrylic anhydride-modified gelatin having a graft substitution rate of 10%, a methacrylamide-modified gelatin having a graft substitution rate of 90%, a methacrylic anhydride-modified gelatin having a graft substitution rate of 40%, a methacrylamide-modified gelatin having a graft substitution rate of 20%, a methacrylic anhydride-modified collagen having a graft substitution rate of 30%, a methacrylic anhydride-modified chondroitin sulfate having a graft substitution rate of 90%, or a methacrylamide-modified carboxymethyl cellulose having a graft substitution rate of 10%, an acryloyl chloride-modified polyethylene glycol having a graft substitution rate of 10%, and a glycidyl methacrylate-modified dextran having a graft substitution rate of 20%.
In some preferred modes, the o-nitrobenzyl-based photo-trigger-modified macromolecule is one of o-nitrobenzyl-modified hyaluronic acid with a graft substitution rate of 100%, o-nitrobenzyl-modified sodium alginate with a graft substitution rate of 50%, o-nitrobenzyl-modified chondroitin sulfate with a graft substitution rate of 10%, o-nitrobenzyl-modified gelatin with a graft substitution rate of 30%, o-nitrobenzyl-modified fibroin with a graft substitution rate of 90%, o-nitrobenzyl-modified collagen with a graft substitution rate of 100% or o-nitrobenzyl-modified chitosan with a graft substitution rate of 10%, and o-nitrobenzyl-modified citric acid Polymer (PEGMC) with a graft substitution rate of 10%.
In some preferred modes, the mass final concentration of the macromolecule modified by the photoresponsive crosslinking group is 3-10% by mass of deionized water, the mass final concentration of the macromolecule modified by the o-nitrobenzyl type photo-trigger is 2-4% by mass of the deionized water, and the mass final concentration of the photoinitiator is 0.03-0.2% by mass of the deionized water.
The invention also provides application of the light-operated 3D printing ink in skin injury repair.
The invention also provides application of the light-operated 3D printing ink in articular cartilage defect repair.
Further, the application is as follows: and printing the light-operated 3D printing ink into a stent by using a Digital Light Processing (DLP) -based 3D printing technology, and implanting the stent into a position with skin defect to realize skin tissue repair.
The invention utilizes the principle that an o-nitrobenzyl optical trigger generates aldehyde group after being excited by illumination, the generated aldehyde group and amino group can react to form a strong chemical bond, meanwhile, macromolecules modified by photoresponsive crosslinking groups are rapidly cured under illumination, the mechanical property is enhanced by double crosslinking networks, and the porous microscopic structure printed by 3D can achieve the purpose of rapidly repairing defects, thereby being an ideal light-operated 3D printing ink for repairing skin defects or osteochondral defects. The material can be in any form, can be in a solid form, and can be directly printed when needed in a liquid form or a liquid form.
The material and the bio-ink may be interchanged, and the material or the ink may include some active components, such as stem cells or other components, and it is also possible to print or process only the material or the ink itself and then add the active components.
Printing apparatus
In some aspects, the present invention provides a printing apparatus, such as the structures illustrated in fig. 13-17. In some aspects, the printing apparatus includes a curing unit having a reservoir 1102 that can contain bio-ink, and coupled to the reservoir can be a feed system and a discharge system. Typically, curing of the light occurs in the bio-ink within the container 1102. In some embodiments, the curing unit or the curing vessel is a stationary device. The printing device further comprises a light path conversion unit 1002 which can move relative to the curing unit and which converts light of the image of the projection device into the curing unit to realize curing printing of the light. In some approaches, the light conversion unit includes a lens 1003 and/or a mirror 10129 to effect the change in direction of the light. In some approaches, the projection device projects an image into the lens 1003, which effects conversion of the optical image from the projection device into parallel light that is reflected by the mirrors and projected into the light curing container 1102 to effect curing of the tube. In some approaches, the mirror may reflect light at one or more different angles to change the path of the light. For example, fig. 17 is a schematic diagram of the optical path transformation in an embodiment of the present invention, and a projection device 1005 projects an image 6000 into a lens 1003, where the image is an image unit after image processing, and the image unit represents the minimum unit required for printing. The light 5003 converted from the lens 1003 incident to the lens 5001 is incident in parallel to the reflective mirror 10129 to realize the first change of the optical path, the light projected to the reflective mirror 10128, the second change of the optical path is realized, and finally the light 5004 is projected to the reflective mirror 10127. The change of the optical direction is achieved to become parallel light which is projected into the curing vessel 1001 for curing of the light. The image of the general image unit 6000 is finally projected into the curing container via the change of the optical path, with the image 5000, the projection of the light achieves the curing of the bio-ink, thereby completing the printing of one image. In some aspects, the unit including the mirrors may be moved circumferentially around the curing vessel 1001, with circumferential movement generally denoting circular movement. The circular motion can be 360 degrees or a certain arc. In some approaches, the mirror is disposed in an optical path channel that effects a change in the direction of the light. The optical path passage 1002 realizes an integral rotational arrangement to be disposed around the rotation of the curing container 1001. The optical path is fixed to a rotating structure 1002, and rotation of the rotating structure causes a change in the optical path, thereby effecting rotation of the optical path. While the rotation 1002 of the rotating structure has a bracket structure 10124, connected to the direct structure is a rotating shaft 10143, which is connected to a stepper motor 1004 to effect rotation of the entire structure. And the radian or angle of rotation is the angle after the digitization process is performed during the image processing segmentation. Of course, when it is required to move the light path channel up and down relative to the curing unit, a motor for driving the light path channel to move up and down is required. The motion of these motors or stepper motors can be automatically controlled by computer software and the parameters controlled can be part of the parameters in the image processed data to know the trajectory and parameters of the motion. Of course, in order to avoid the external light from entering the light path channel or interfering the light of the projection image of the projection device, a totally enclosed channel can be implemented between the projection device and the lens or the light path channel, so as to avoid the external light from entering. In the light curing unit is projected through the reflected light, tight fit is also realized, and external stray light is prevented from entering so as to interfere with the curing of the light.
In some modes, the device also comprises a rotation angle monitoring device which is used for monitoring the change of the angle, so that the change degree of the angle is input into a computer, and the angle of the projected image is adjusted through the calculation of the computer, so that the angle between the images actually projected to the curing container is consistent with the angle of the designed image, and the precision of the printing angle is ensured.
Advantageous effects
The advantages of the invention for a newly designed printer are:
1. the use of a plurality of feed units and ejection of compact unit can realize adopting multiple material to print conveniently, can imitate natural tissue and organ multicomponent characteristic better.
2. The feed inlet of the feeding unit and the discharge outlet of the discharging unit are arranged on the outer side of the bottom of the quartz resin tank, so that the influence of the flow of the biological ink on the formed structure during feeding and discharging can be minimized.
3. The volume projection imaging principle is used for photocuring biological ink, and integrated printing of a target structure can be realized, rather than stacking layer by layer from top to bottom or from bottom to top. This allows more complex structures to be printed, which better mimic the complex structures of natural tissues and organs.
4. In the whole printing process, the quartz resin groove does not need to be moved, so that the shape of the printing structure is more stable.
Drawings
Fig. 1 is a schematic structural diagram of a feeding system, a material pool and an upgrading platform of the invention.
Fig. 2 is a schematic flow chart of printing an 8-color microcube.
Fig. 3 is a projection picture of a batch printed array of cell cubes 1 and 5 in an 8-color microcube.
Fig. 4 is a projection picture of a batch printed array of cell cubes 2 and 6 in an 8-color microcube.
Fig. 5 is a projection picture of a batch printed array of cell cubes 3 and 7 in an 8-color microcube.
Fig. 6 is a projection picture of a batch printed array of cell cubes 4 and 8 in an 8-color microcube.
Fig. 7 is an optical microscope photograph of an 8-color microcube batch printed by the printing flow of fig. 2.
FIG. 8 is a schematic diagram of a three-dimensional modeled three-dimensional structure of a printed subject according to an embodiment of the present invention.
FIG. 9 is a three-dimensional model diagram of the superstructure of the structure shown in FIG. 8.
FIG. 10 is a three-dimensional model of the underlying structure of the structure shown in FIG. 8.
Fig. 11 is a schematic diagram of a division manner of image processing of the upper layer structure of fig. 8.
FIG. 12 is a photographic image under a microscope of a physical representation of the structure shown in FIG. 8 printed by the printing method of the present invention.
Fig. 13 is a perspective view showing a configuration of a printing apparatus according to an embodiment of the present invention.
Fig. 14 is an exploded structural view of a printing apparatus in an embodiment of the present invention.
Fig. 15 is a schematic perspective view of a light conversion unit capable of relative movement according to an embodiment of the present invention.
Fig. 16 is a sectional view of a light conversion unit relatively moving and a sectional structure diagram of a curing container in an embodiment of the present invention.
FIG. 17 is a schematic diagram of the optical path change of an embodiment of the present invention.
Fig. 18 is a schematic view of the principle of the angular adjustment of the projected image.
Fig. 19 is a schematic view of a structure for keeping the direction of light for projecting an image constant.
Fig. 20 is a top view of the structure of fig. 19.
Fig. 21 is a schematic diagram of a method for image processing of angle change in rotation angle measurement.
Detailed Description
The present invention provides specific embodiments to illustrate the printing method of the present invention, and it should be understood that these embodiments are merely illustrative of how to implement the present invention and should not be construed as limiting the present invention, and the scope of the present invention is defined by the appended claims.
Example 1: fast batch for 8-color microcubesVolume printing
Preparation of biological ink 1) 75mg of o-nitrobenzyl modified hyaluronic acid (HA-NB), 250mg of methacrylic anhydride modified gelatin (GelMA) and 10mg of phenyl (2,4, 6-trimethylbenzoyl) lithium phosphate (LAP) are dissolved in 10ml of deionized water to prepare the light-controlled 3D printing ink containing 0.75% of HA-NB, 2.5% of GelMA and 0.1% of LAP.
The structure of printing apparatus is as shown in fig. 1, and the left side is the top view, and the right side is the stereogram, has 3 discharge gates A, B, C, gets rid of different inks respectively, and lift platform is located the higher authority of printing the pond, and light is projected in printing the pond from below, when printing the object of different materials, can conveniently get rid of different inks, and the kind of ink can conveniently be changed, can not cause the pollution between the ink. The printed material is more accurate. The structure of the printed object is also complicated by the different kinds of ink.
For example, as shown in fig. 2, a model of an array of four unit cubes is created, projection pictures of the four unit cubes are shown in fig. 3 to 6, and then program control is performed according to the created model, followed by printing. The printing steps are as follows:
1. the layer thickness is set first, e.g. 50um on a side of the unit cube, then the layer thickness is set to 50um (e.g. number 1 in fig. 2);
2. supplying ink A with a layer of thickness, and selecting a position 1 unit cube model to perform projection exposure printing;
3. sucking away uncured ink a;
4. keeping the layer thickness height unchanged, supplying a layer of material B with the thickness, and selecting a position 2 cube model to perform projection exposure printing (for example, the position of the number 2 in the figure 2 is performed);
5. sucking away uncured ink B;
6. repeating the steps 2-5 until the first layer structure is completely printed, wherein the serial numbers of 3 and 4 in the figure 2 are printed;
7. raising the sample platform by one layer of height;
8. selecting a unit cube model at a selected position 1 for projection exposure printing of a material E with two thicknesses (for example, the number 5 in FIG. 2);
9. sucking away uncured ink E;
10. and (3) repeating the steps (8-9) until the second layer structure is completely printed ( numbers 5,6,7 and 8 in the figure 2), finishing printing the 8-color micron cubes, and finally obtaining the 8-color micron cubes printed in batch as shown in the figure 7, wherein the exposure light intensity is 50, and the exposure time of each layer is 1000 ms. This can facilitate the implementation of a color printing architecture. Wherein reference numerals 1,5,6,2 denote structures formed by different inks.
The image projection can adopt the image processing unit of the invention to carry out image processing in advance, then the image is output through the projection device and projected into the printing pool, and the projected image is directly subjected to light curing. For example, the different numbers in fig. 2 may be a projected image in which a plurality of identical images are printed in superposition. For example, if the number 1 has 50um, and if the thickness of each image is 5um, 10 identical images are projected in succession to perform light curing, and the number 1 can be printed. By analogy, when the number 2 is another bio-ink, 10 identical projection images 2 are printed with different bio-inks, and the printing of the number 2 is obtained. Thus, although the material is different between the ink of the number 1 and the ink of the number 2, this method is more complicated in view of the understanding, but the structure of the printing is more complicated, and the structure is closer to the structure of the living body itself, which makes it possible to replace the organ of the living body.
Example 2: 3D printing cartilage support for osteochondral defect repair
For example, as shown in fig. 8, 9 and 10, the target structure to be printed is modeled, and then program control is carried out according to the established model, so as to carry out 'color' volume imaging printing of different materials at different parts of the bracket.
For example, the created model is shown in fig. 8, 9 and 10, and fig. 8 is a cartilage scaffold model, which is composed of two parts, an upper scaffold of fig. 9 and a lower scaffold of fig. 10. Wherein the upper layer bracket is provided with 30 round holes in overlook, the side surface is also provided with 30 round holes, and the round holes are crossed and communicated.
Taking the above layer structure as an example, the cutting manner of the model according to the present embodiment is shown in fig. 11. The image is cut along the center point 105 and digital information is entered in the image processing system. The cutting position may be a longitudinal cut 106, cutting at different angles along the entire cylinder 100, for example, at 1 degree arc, cutting into virtually infinite rectangular parallelepiped faces, except that some faces have no notches, some have notches, the absence of notches indicates no holes are formed, and the presence of notches has holes. The notch can be in the interior of the rectangular parallelepiped or at the edge of the rectangular parallelepiped. For example, every 1 deg. cut, 360 faces can be formed in practice, and 720 faces can be formed if the cut is at an angle of 0.5 deg.. How to cut and the cut image can be automatically finished in software, so that digital information of different surfaces is formed, and very accurate image construction can be realized. The digital information is projected by a projector, each projection is a cut surface, light of the surface is optically reflected and irradiates the container with the bio-ink, an image of the cut surface is formed in the container with the bio-ink, and the light with focus can be cured due to curing, while the light without focus can pass through the ink without curing. Like this, form the face of a cuboid in biological ink, because the dimension of 360 degrees goes on, so, each solidification face forms the back, needs rotatory optical path system, lets the position of focus change, along with constantly rotating, accomplishes 360 rotations, has accomplished the focus solidification of a plurality of different faces to finally accomplish the printing of whole model.
If different structures or structures are arranged or the structures of each surface are different, ink can be removed after one surface is formed, and new different ink can be injected to form another surface, wherein the surface can be the surface with different heights, different thicknesses and different structures. Thus, color printing can be conveniently realized.
The scaffold is designed for cartilage repair, and the lower scaffold has 30 holes in plan view, so that the aim of migrating bone marrow mesenchymal stem cells to the upper layer is to help cartilage repair. For the design of the upper layer scaffold, the middle hole is used for enabling bone marrow mesenchymal stem cells to migrate to a cartilage layer, and the side holes are used for enabling chondrocytes to migrate to a damaged part, so that cartilage defects are repaired better.
The proportions of the biological ink adopted by the upper layer and the lower layer of the bracket structure are respectively as follows:
and (3) upper ink layer: the upper layer is methacrylic anhydride grafted silk fibroin (SilMA) with a concentration of 15%. The photosensitizer is 10% v/v, and the concentration of phenol red is 0.8%;
ink of the lower layer: the lower layer was 8M methacrylic anhydride grafted gelatin (GelMA) at 15% concentration. The photosensitizer was 10% v/v, phenol red concentration 0.8%. The configuration process comprises the following steps:
the printing process is described as an example of a model as shown in fig. 8, using two biomaterials, as follows: taking the lower layer of the bracket as an example, and the upper layer of the bracket as an example, the printing method adopting two biological materials according to the cartilage bracket model comprises the following steps:
processing of the image:
the target printing structure is created by modeling with CAD software, and may be, for example, a columnar structure with upper and lower layers, such as the upper and lower side structures shown in FIG. 8, or a three-dimensionally constructed structure with different internal structures.
2. The upper and lower layers of the model are separated and exported to the format files of the upper layer structure (upper.stl) and the lower layer structure (bottom.stl), respectively, as shown in fig. 9 and 10.
3. The stl files of upper and bottom are read using the software Matlab.
4. The Image Processing Toolbox in the software Matlab is used to segment the images of both the upper and bottom 3D models.
5. The two models of upper and bottom are image fused by using the ImageBlendingPackage in the software Matlab, and the holes are corresponding.
6. Finding out the central symmetry axes of the upper model and the bottom model, making a plane containing the symmetry axes, and outputting the mapping of the 3D model on the plane;
7. rotating the plane clockwise, cutting once every certain same angle, as shown in fig. 11, and after the cutting process is completed in a circulating manner, obtaining a processed result file.
Step 1: respectively slicing the upper layer and the lower layer of the 3D cartilage support model, wherein the graph of each slice is used as the illumination graph of the layer; and (3) respectively loading the two biological inks into a feeding unit according to the requirements of the printed object, and aligning the bottom of an image obtained by projection of the lower layer slice with the bottom surface of the resin tank at the beginning.
And 2, injecting the biological ink GelMA into the resin tank from the lower part of the quartz resin tank by the supply unit 1 filled with GelMA, wherein the height of the biological ink is slightly larger than the height of the lower-layer structure, and the height of the biological ink is actually consistent with the height, the volume or the shape of the formed structure). The stepping motor 1004 rotates the mirror 10129,10128,10127 and the cube 1101 in synchronization, and the projector 1005 and the ink container 1102, such as a resin tank, are fixed. The centers of rotation of the mirror and the cube coincide with the geometric center 5002 of the resin bath. And according to the preset angle interval of the image processing system, the stepping motor drives the reflector and the square box to rotate by an angle in the same direction every time the stepping motor rotates by an angle, and meanwhile, the projector quickly switches to the next projection image to complete exposure in one projection direction. After 360-degree exposure, specific exposure distribution is formed in the resin tank, the position exceeding the GelMA photocuring exposure threshold of the biological ink is cured and formed, and the rest positions are still liquid, so that the printing of the lower layer structure is completed. Here also the lens 1003 is stationary.
And step 3: the discharging unit completely pumps out the uncured biological ink GelMA from the bottom of the resin tank. The feed unit 2 containing the SilMA then injects 11021 bio-ink, which has a height slightly greater than the top surface of the superstructure corresponding to the height of the resin bath, into the curing container from below the quartz resin bath, for example the resin bath. At the moment, the projection of the upper layer structure and the upper part of the lower layer structure are slightly overlapped so as to ensure the stable connection between the upper layer structure and the lower layer structure. The stepping motor drives the reflector and the square box to synchronously rotate, and the projector and the curing container are not moved. The centers of rotation of the mirror and the cube coincide with the geometric center 5002 of the resin bath. And according to the preset angle interval of the image processing system, the stepping motor drives the reflector and the square box to rotate by an angle in the same direction every time the stepping motor rotates by an angle, and meanwhile, the projector quickly switches to the next projection image to complete exposure in one projection direction. After 360 degrees of exposure, specific exposure distribution is formed in the resin tank, the position exceeding the photo-curing exposure threshold value of the bio-ink SilMA is cured and formed, and the rest positions are still liquid, so that the printing of the upper layer structure is completed.
And 4, step 4: the discharging unit completely pumps out the uncured bio-ink SilMA from the bottom of the resin tank. The entire stent completes printing.
FIG. 11 is a microscopic structure of each layer, in which top views of different cavity sizes can be seen, and side holes and top-view holes are arranged identically to each other. Meanwhile, a fluorescence structure diagram of 400um is observed under a fluorescence microscope.
The invention shown and described herein may be practiced in the absence of any element or elements, limitation or limitations, which is specifically disclosed herein. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, and it is recognized that various modifications are possible within the scope of the invention. It should therefore be understood that although the present invention has been specifically disclosed by various embodiments and optional features, modification and variation of the concepts herein described may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
Claims (10)
1. The 3D printing device based on the imaging principle comprises an optical path conversion unit, a light path conversion unit and a control unit, wherein the optical path conversion unit can project one or more images generated by a projection device into a curing unit for curing; wherein the apparatus further comprises a rotation angle measuring device for measuring the angle of rotation of the optical path conversion unit around the curing unit; the device also comprises a computer system, a polarizing unit and a control unit, wherein the computer system is used for adjusting the angle of the projected image by the angle measured by the angle measuring device, the polarizing unit is arranged at the periphery of the curing unit and comprises a glass prism and a cylindrical lens, one surface of the glass prism is arc-shaped and is attached to the surface of the curved surface of the curing unit, and the rest is a plane; oil with the same refractive index as that of the prism is filled at the joint of the curing unit and is used for lubricating during light penetration and rotation; the cylindrical lens is used to compensate for a shift of an image focal plane caused by a refractive index deviation between the glass prism and the ink.
2. The 3D printing apparatus as claimed in claim 1, wherein the curing unit is an ink container containing bio-ink, and the image is projected into the ink container.
3. The 3D printing apparatus according to claim 1, wherein the optical path conversion unit and the curing unit are positioned in a relative rotational arrangement.
4. The 3D printing apparatus according to claim 1, wherein the curing unit is stationary and the light path converting unit is disposed in a circular motion around the curing unit.
5. The 3D printing apparatus according to claim 2, wherein the optical path conversion unit projects the projection image into the curing unit by reflection of light.
6. The 3D printing device according to claim 5, wherein the reflected light is perpendicular to the curing unit.
7. The 3D printing device according to claim 1, wherein a longitudinal axis of the curing unit is perpendicular to an image axis of the projection device.
8. The 3D printing device according to claim 2, wherein the device further comprises a cartridge containing an ink container, the cartridge surrounding the ink container, and a liquid having a refractive index similar to that of the ink being contained between the ink container and the cartridge.
9. The 3D printing apparatus according to claim 1, wherein the optical path conversion unit includes a lens and/or a mirror.
10. The 3D printing apparatus according to claim 1, wherein the optical path conversion unit includes a mirror.
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| US17/616,041 US20220324163A1 (en) | 2019-06-04 | 2019-07-24 | Imaging principle-based integrated color light 3d bioprinting system |
| PCT/CN2019/097471 WO2020244037A1 (en) | 2019-06-04 | 2019-07-24 | Imaging principle-based integrated color light 3d bioprinting system |
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| CN1850494A (en) * | 2006-05-22 | 2006-10-25 | 西安交通大学 | Digital projection photocurable rapid shaping apparatus and method |
| ITGE20130027A1 (en) * | 2013-03-04 | 2014-09-05 | Smart3D Net Di Dotta Andrea E Gie Andrea Snc | METHOD AND DEVICE FOR THE PRODUCTION OF OBJECTS THROUGH STEREOLITHOGRAPHY |
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