A 4D printing method for complex branching blood vessel structures based on illumination

Abstract

The application provides a 4D printing method for complex branched blood vessel structure based on illumination. The printing method is to obtain a precursor solution by dissolving and mixing a compound having a ortho-nitrobenzyl four-arm polyethylene glycol and a methacrylated hyaluronic acid with PBS; a modeling software is used to create a tube model of the complex branched blood vessel, wherein the tube model comprises a Y-shaped tube model, a T-shaped tube model, a first-stage branched tube model and a second-stage branched tube model; the prepared precursor solution is put into a DLP printer tank, material printing is performed according to a design scheme based on the tube model to be printed to form a tube piece structure, the tube piece structure is completely soaked in a PBS solution to self-curl to form a complex branched blood vessel structure, and the complex branched blood vessel structure is subjected to secondary crosslinking under ultraviolet light to form a closed complex branched blood vessel structure. The printing model of the complex pipeline is designed, integrated printing is performed, the model design of the connection is decoupled by changing the radial expansion characteristics of the 4D material to realize the self-curling curvature of the complex closed pipeline, and the 4D printing of the complex closed pipeline is realized.

Description

Technical Field

[0001] This invention belongs to the field of 4D printing technology, specifically a 4D printing method for complex blood vessel structures based on illumination. Background Technology

[0002] The engineering of functional artificial tissues and organs, biologically similar to their in-body counterparts, is crucial for healing or replacing damaged or necrotic tissues / organs and may fill the gap between organ shortages and transplant needs. Now, 3D printing technology can manufacture tissue-engineered products with precisely controllable components, resulting in biomimetic bodies with spatial distribution and structure to achieve effective replacements with the characteristics and biological functions of target tissues and organs. These physiological substitutes will ultimately advance the prevention, diagnosis, and molecular therapy of diseases.

[0003] While 3D printing holds immense potential for creating complex bio-alternatives, fabricating vascular systems remains challenging, particularly the hollow tubular structures that form the fundamental building blocks of the vascular system. Common methods for manufacturing hollow tubular structures include: 1. using sacrificial materials; 2. printing scaffolds with interconnected channels; and 3. using coaxial needles for 3D printing. Although these techniques can form hollow tubular structures, several issues remain: firstly, the printing cost is high; secondly, the structures are static and lack biomimicry; and thirdly, existing methods cannot print flowable structures with complex branching vascular morphologies.

[0004] 4D printing can overcome the limitations of 3D printing in creating tubular structures. The concept of "4D printing," proposed by Skylar Tibits at TED, defines the fourth dimension as "time." In tissue engineering, 4D printing means that structures can self-change shape when exposed to predetermined stimuli (such as light, temperature, magnetic fields, pH, and certain specific chemicals). 4D printing has made significant progress in recent years, becoming a new hot topic in tissue engineering. Vascular grafts are the first biologically relevant application of 4D printing in tissue engineering because tubular structures can be easily obtained through rolling or self-stretching processes. In a recent paper, Professor Ionov's lab at the University of Bayreuth used DIW-based printing to obtain tubular structures with inner diameters as low as 20 μm through self-folding using photocrosslinking gradients. Due to the same self-folding mechanism, their lab also achieved the formation of hollow tubular structures in the form of scalable-diameter T-joints, with connecting bridges printed at the T-tube connections. Despite the promising results achieved in vascular grafts, 4D printing complex small-diameter closed branch tubular structures in a one-piece molding manner remains challenging. The following problems exist in 4D printing complex closed branch tubular structures in a one-piece molding manner: (1) Due to the incompatibility of boundary curvature, the curvature of the model connection is uncontrolled after curling, making it difficult to close the complex tubular connection after curling, and leakage is easy to occur at the connection during perfusion; (2) It is difficult to form cross-links at the edge of the tubular structure formed by 4D printing to form a completely closed tubular structure after curling; (3) Existing complex pipe designs are not universal and can only be applied to a certain specific tubular structure. Summary of the Invention

[0005] To address the problems existing in the background technology, this invention provides a 4D printing method for complex branched vascular structures based on illumination. This method is based on the design of a model that can fabricate complex hollow closed tubes through photocrosslinking. By transforming the shape of the corresponding model through 3D printing, a tubular structure with complex closed branches is obtained. This invention achieves complex branched vascular structures by combining gradient formation and secondary crosslinking.

[0006] To achieve the above technical objectives, this invention provides a 4D printing method for complex branched blood vessel structures based on illumination, characterized in that the printing method includes the following steps:

[0007] (1) Preparation of printing raw materials: The tetra-arm polyethylene glycol with o-nitrobenzyl group and methacrylated hyaluronic acid are dissolved and mixed in PBS to obtain a 4D printing precursor solution, wherein the mass concentration of the tetra-arm polyethylene glycol with o-nitrobenzyl group is 10-15% and the mass concentration of methacrylated hyaluronic acid is 2-4%.

[0008] (2) Use Shapr3D three-dimensional modeling software to create tube models of complex branching blood vessels. The tube models include Y-type tube models, T-type tube models, primary bifurcation tube models and secondary bifurcation tube models.

[0009] (3) Place the precursor solution prepared in step (1) into the material tank of the DLP printer, and print the material into a tube structure based on the tube model to be printed according to the design scheme. The thickness of the tube structure is 500μm. The printing parameters are as follows: light intensity 20mW / cm 2 The model slice thickness is 500μm, and the exposure time is 960~2100s; the light intensity and exposure time are the curing parameters of a single layer of model structure, with one base layer and one sheet layer.

[0010] (4) The tube structure printed in step (3) is taken out and completely immersed in PBS solution. The structure completes the self-rolling to form a complex branching blood vessel structure. It is then subjected to secondary cross-linking under ultraviolet light in PBS solution to form a closed complex branching blood vessel structure. The complex branching blood vessel structure includes Y-shaped tubes, T-shaped tubes, primary branching tubes or secondary branching tubes.

[0011] The preferred technical solution of the present invention describes a Y-shaped pipe model composed of three main pipe segments spliced ​​together. The connection parts of the three main pipe segments are provided with semi-circular connecting pieces of the same size, and the convex areas of the semi-circular connecting pieces of the three main pipe segments are interconnected. The T-shaped pipe model is composed of two main pipe segments spliced ​​together to form a T shape. The vertical area of ​​the main pipe segments spliced ​​together is provided with a semi-circular connecting piece, and the horizontal area of ​​the main pipe segments is provided with a semi-elliptical interface that matches the diameter of the T-shaped pipe.

[0012] The preferred technical solution of this invention describes a primary branch pipe model composed of a main pipe segment and primary branch pipe segments. The primary branch pipe segment connects to one side of the main pipe segment and has a semi-circular connecting piece at its end with the same angle as the angle between the main pipe and the primary branch pipe of the primary branch pipe to be printed. A semi-elliptical interface is provided on the opposite side of the main pipe segment. This semi-elliptical interface is compatible with the primary branch pipe segment after it has been rolled up. The major axis of the semi-elliptical interface is equal to the length of the overlapping portion of the rolled-up primary branch pipe segment and the main pipe, and is parallel to the major axis of the main pipe. The minor axis of the semi-elliptical interface is the outer diameter of the primary branch pipe, and is perpendicular to the major axis of the main pipe. The secondary branch pipe model has a secondary branch pipe segment on one side of the primary branch pipe segment of the primary branch pipe model. The end of the secondary branch pipe segment has a semi-circular connecting piece matching the inclination angle of the secondary branch pipe. A semi-elliptical interface compatible with the rolled-up secondary branch pipe segment is provided on the other side of the primary branch pipe segment.

[0013] The preferred technical solution of the present invention is as follows: the precursor solution in step (1) has a mass concentration of 10% of o-nitrobenzyl tetraarm polyethylene glycol and a mass concentration of 2% of methacrylated hyaluronic acid; the exposure time during printing in step (3) is 960s.

[0014] In the preferred embodiment of the present invention, step (4) involves performing secondary crosslinking in the PBS solution using ultraviolet light. Irradiate the self-curling, complex branching vascular structures immersed in PBS solution with ultraviolet light for 5–6 minutes.

[0015] In the preferred embodiment of the present invention, the two main pipe segments of the T-shaped pipe model are rectangular, and the center of the semi-elliptical notch on one of the main pipe segments is on the same straight line as the major axis of the other main pipe segment; the three main pipe segments of the Y-shaped pipe model are rectangular, and the major axes of the three rectangular main pipe segments form an angle of 120° with each other, and the intersection points of the semi-circular connecting pieces form a closed shape.

[0016] The preferred technical solution of the present invention is as follows: when the branch pipe of the pipe model is vertical in the middle, the pipe segment connection uses a semi-circular connection. The major axis of the semi-elliptical notch on the main pipe segment is 1 / 4 of the branch pipe, the major axis is perpendicular to the major axis of the main pipe, the minor axis is the outer diameter of the branch pipe, and the minor axis is parallel to the major axis of the main pipe.

[0017] This invention uses a mixture of four-arm polyethylene glycol (PEGNB) with o-nitrobenzyl groups and methacrylated hyaluronic acid (HAMA) with double bonds as printing materials. A printing model was designed, and DLP (Digital Light Projection) printing was used to achieve the deformation of complex branching vascular structures under solution stimulation. This mixed printing material was printed without a photocrosslinking agent. After the printed structure was stimulated and curled with solution (PBS), due to the decrease in light energy from the near-light source side to the far-light source side, and the lower degree of reaction on the far-light source side compared to the near-light source side, the curled structure has the characteristic of secondary photocrosslinking on the far-light source side. The printed structure formed after photocrosslinking of the photocurable material in 4D printing exhibits radial expansion characteristics.

[0018] Because the printed structure exhibits radial expansion, this invention addresses the incompatibility of curvature at the joints when 4D-printed complex pipe structures curl under stimulation. It employs a semi-circular connection at the joint, minimizing overlap. Upon stimulation with a solution (PBS), the connection expands radially, ensuring the curling force is perpendicular to the pipe's long axis, thus decoupling the self-curving curvature and allowing the two pipes to curl almost independently. Furthermore, the printed structure's ability to undergo secondary photocrosslinking after solution stimulation allows the curled pipes to be photocrosslinked in the solution to close the curled edges, forming a closed, complex branching pipe structure.

[0019] The beneficial effects of this invention are:

[0020] (1) The printing material used in this invention adopts the PEGNB-HAMA system. After the PEGNB-HAMA system is cured, the reaction degree is different from the near light source side to the far light source side. When immersed in the solution, it will produce different degrees of spontaneous swelling, causing the printed structure to self-curl and realize the autonomous deformation of the printed structure.

[0021] (2) After the PEGNB-HAMA system in this invention is cured, due to the different reaction degrees on the near light source side and the far light source side, there is still residual material on the far light source side that can be reacted. It has secondary cross-linking characteristics and can be used for post-processing after the printed structure is deformed to achieve the airtightness of the printed pipe.

[0022] (3) The 4D printing preparation method of the present invention can undergo four-dimensional transformation under mild solution stimulation; based on the radial expansion characteristics of 4D materials after receiving stimulation, a printing model of complex pipes is designed and printed in an integrated manner; the connection of different types of complex tubular structures is composed of different semi-circular joints and semi-elliptical notches. When appropriate stimulation is applied, the curling curvature of the pipe connection is decoupled, and the pipes curl independently but are connected to each other. After the connection is curled, it fits due to its swelling properties, and then the entire edge of the complex pipe is sealed through secondary cross-linking; therefore, the 4D printing of complex sealed pipes can be achieved by changing the model design of the connection to decouple the self-curving curvature through the radial expansion characteristics of 4D materials. Attached Figure Description

[0023] Figure 1 It is the T-tube model in Example 1;

[0024] Figure 2 It is the T-shaped tube 4D printed in Example 1;

[0025] Figure 3 It is the Y-shaped tube model in Example 2;

[0026] Figure 4It is the Y-shaped tube 4D printed in Example 2;

[0027] Figure 5 This is the first-stage bifurcation pipe model in Example 3;

[0028] Figure 6 It is the first-stage branching tube 4D printed in Example 3.

[0029] Figure 7 This is the secondary branching pipe model in Example 4;

[0030] Figure 8 It is the secondary branching tube 4D printed in Example 4. Detailed Implementation

[0031] The present invention will be further described below with reference to the accompanying drawings and embodiments. Figures 1 to 8 All accompanying drawings are simplified versions of embodiments and are intended only to clearly and concisely illustrate the embodiments of the present invention. The technical solutions shown in the drawings below are specific solutions of embodiments of the present invention and are not intended to limit the scope of the claimed invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0032] The complex branching vessel tube models in this embodiment of the invention include Y-shaped tube models, T-shaped tube models, primary branching tube models, and secondary branching tube models; ultimately, Y-shaped tubes, T-shaped tubes, primary branching tubes, or secondary branching tubes are printed. The Y-shaped tube model is composed of three main tube segments joined together. Each of the three main tube segments has a semi-circular connecting piece of the same size at its connection point, and the convex areas of the semi-circular connecting pieces are interconnected. The intersection points of the semi-circular connecting pieces form a closed shape. The three main tube segments of the Y-shaped tube model are rectangular, and their major axes form an angle of 120° with each other. The T-shaped tube model is composed of two main tube segments joined together to form a T-shape. The vertical area of ​​the main tube segments has a semi-circular connecting piece at the joint, and the horizontal area of ​​the main tube segments has a corresponding semi-elliptical interface matching the diameter of the T-shaped tube. The two main tube segments of the T-shaped tube model are rectangular, and the center of the semi-elliptical notch on one main tube segment is collinear with the major axis of the other main tube segment.

[0033] The primary branch pipe model is composed of a main pipe segment and primary branch pipe segments. Each primary branch pipe segment connects to one side of the main pipe segment and has a semi-circular connecting piece at its end that has the same angle as the angle between the main pipe and the primary branch pipe of the primary branch pipe to be printed. A semi-elliptical interface is located on the opposite side of the main pipe segment. This semi-elliptical interface is compatible with the curled primary branch pipe segment. The major axis of the semi-elliptical interface is equal to the length of the overlapping portion of the curled primary branch pipe segment and the main pipe, and is parallel to the major axis of the main pipe. The minor axis of the semi-elliptical interface is the outer diameter of the primary branch pipe, and is perpendicular to the major axis of the main pipe. The secondary branch pipe model has a secondary branch pipe segment on one side of the primary branch pipe segment of the primary branch pipe model. The end of the secondary branch pipe segment has a semi-circular connecting piece with a matching inclination angle. A semi-elliptical interface compatible with the curled secondary branch pipe segment is located on the other side of the primary branch pipe segment. When the branch pipe of the pipe model is vertical in the middle, the pipe segment connection uses a semi-circular connection. The major axis of the semi-elliptical notch on the main pipe segment is 1 / 4 of the branch pipe, and the major axis is perpendicular to the major axis of the main pipe. The minor axis is the outer diameter of the branch pipe, and the minor axis is parallel to the major axis of the main pipe.

[0034] Example 1 describes a 4D printing method for T-shaped blood vessel structures. The specific printing process is as follows:

[0035] (1) Preparation of PEGNB / HAMA precursor solution: Four-arm polyethylene glycol (PEGNB) with o-nitrobenzyl group and methacrylated hyaluronic acid (HAMA) with double bond are dissolved and mixed in PBS solution to form a printing precursor solution. The mass concentration of four-arm polyethylene glycol with o-nitrobenzyl group in the precursor solution is 10%, and the mass concentration of methacrylated hyaluronic acid is 2%.

[0036] (2) Create a T-shaped pipe model using Shapr3D 3D modeling software, such as Figure 1 As shown, the T-tube model consists of two rectangular sheet structures. The area where the two rectangular sheet structures connect uses a semi-circular structure, and a semi-elliptical notch is designed at the tangent position of the semicircle at one end to adapt to the rolled-up tubular structure. Rectangular sheet 1 is 13mm long and 5mm wide; rectangular sheet 2 is 10.4mm long and 4mm wide. The semi-circular connection diameter is equal to the shorter side length of the rectangle (5mm). The minor axis of the semi-elliptical notch is approximately 4 / 2π≈0.64mm, the major axis is 4 / 4=1mm, and the major axis is perpendicular to the major axis of the rectangle. The center of the semi-elliptical notch is on the same straight line as the major axis of rectangular sheet 2. The overall thickness of the model is 0.5mm. The 3D model is saved in STL format.

[0037] (3) Place the precursor solution into the feed tank of the DLP printer, import the T-tube model into the DLP printer, and print according to the model design; the printing parameters are: light intensity 20mW / cm². 2 Exposure time: 960s; slice thickness: 500μm; number of base layers: 1; peel distance: 6mm; lifting height: 0mm; peel speed: 18mm / min; lifting speed: 100mm / min; peel recovery speed: 180mm / min.

[0038] (4) After the model is printed as a whole, it is removed. After the printed structure is photocured, the organic matter on the upper and lower surfaces generates a wettability gradient due to the reaction. When it is immersed in water, the swelling on the side closer to the light source is greater than the swelling on the side farther from the light source. The extension axis of the structure undergoes self-curling to form a T-shaped tube structure. The T-shaped tube structure is then irradiated with ultraviolet light in the solution. Forming a closed T-tube structure, such as Figure 2 As shown.

[0039] Example 2 describes a 4D printing method for Y-shaped blood vessel structures. The specific printing process is as follows:

[0040] (1) Preparation of PEGNB / HAMA precursor solution: Four-arm polyethylene glycol (PEGNB) with o-nitrobenzyl group and methacrylated hyaluronic acid (HAMA) with double bond are dissolved and mixed in PBS solution to form a printing precursor solution. The mass concentration of four-arm polyethylene glycol with o-nitrobenzyl group in the precursor solution is 10%, and the mass concentration of methacrylated hyaluronic acid is 2%.

[0041] (2) A Y-shaped pipe model was created using Shapr3D 3D modeling software. The Y-shaped pipe model is as follows: Figure 3 As shown, the model comprises three rectangular sheet-like structures. The areas where these three rectangular sheet-like structures intersect use a semi-circular structure. Each rectangular sheet is 13mm long and 5mm wide. The diameter of the semi-circular connection is equal to the shorter side length of the rectangle (5mm). The major axes of the three rectangles form an angle of 120° with each other. The intersection points of the semi-circles form a closed shape. The overall thickness of the model is 0.5mm. The 3D model is saved in STL format.

[0042] (3) Place the precursor solution into the feed tank of the DLP printer, import the Y-shaped tube model into the DLP printer, and print according to the model design; the printing parameters are: light intensity 20mW / cm2, exposure time 960s, slice thickness 500μm, number of base layers 1, peel distance 6mm, lifting height 0mm, peel speed 18mm / min, lifting speed 100mm / min, peel recovery speed 180mm / min.

[0043] (4) After the model is printed as a whole, it is removed. According to this embodiment, after the printed structure is photocured, the organic matter on the upper and lower surfaces generates a wettability gradient due to the reaction. When it is immersed in water, the swelling on the side closer to the light source is greater than the swelling on the side farther from the light source. The extended axis of the structure undergoes self-curling to form a Y-shaped tube structure. The Y-shaped tube structure is then further irradiated with ultraviolet light in the solution. Forming a closed Y-shaped tube structure, such as Figure 4 As shown.

[0044] Example 3 describes a 4D printing method for primary bifurcation blood vessel structures. The specific printing process is as follows:

[0045] (1) Preparation of PEGNB / HAMA precursor solution: Four-arm polyethylene glycol (PEGNB) with o-nitrobenzyl group and methacrylated hyaluronic acid (HAMA) with double bond are dissolved and mixed in PBS solution to form a printing precursor solution. The mass concentration of four-arm polyethylene glycol with o-nitrobenzyl group in the precursor solution is 10%, and the mass concentration of methacrylated hyaluronic acid is 2%.

[0046] (2) A primary bifurcation pipe model was created using Shapr3D 3D modeling software. The primary bifurcation pipe model is as follows: Figure 5 As shown, the model includes two rectangular sheet-like structures. The area where the two rectangular sheet-like structures connect uses a semi-circular structure, and a semi-elliptical notch is designed at the tangent position of the semicircle at one end to adapt to the connection with the rolled-up tubular structure. Rectangular sheet 1 is 13mm long and 5mm wide, while rectangular sheet 2 is 10.4mm long and 4mm wide. The major axes of the two rectangular sheets form a 45° angle. The semi-circular connection diameter is equal to the shorter side length of the rectangle (5mm). The minor diameter of the semi-elliptical notch is approximately 4 / 2π ≈ 0.64mm, the outer diameter of the rolled-up tubular structure, and the major diameter is the overlap length between the semi-circular connecting plate of rectangle 2 and rectangle 1. The upper and lower tangents of the semi-ellipse are parallel to the shorter side of the rectangle, and their intersection points with the semicircle are at the same horizontal level. The overall thickness of the model is 0.5mm. The 3D model is saved in STL format.

[0047] (3) Place the precursor solution into the feed tank of the DLP printer, import the primary branching tube model into the DLP printer, and print according to the model design. The printing parameters are: light intensity 20mW / cm2, exposure time 960s, slice thickness 500μm, number of base layers 1, peel distance 6mm, lifting height 0mm, peel speed 18mm / min, lifting speed 100mm / min, peel recovery speed 180mm / min.

[0048] (4) The model is removed after overall printing. According to this embodiment, after the printed structure is photocured, the organic matter on the upper and lower surfaces generates a wettability gradient due to the reaction. When immersed in water, the swelling near the light source is greater than the swelling away from the light source, and the extended axis of the structure self-curls to form a primary bifurcated tube structure. The primary bifurcated tube structure is then further irradiated with ultraviolet light in the solution. Forming a closed primary branching tube structure, such as Figure 6 As shown.

[0049] Example 4 describes a 4D printing method for secondary bifurcation blood vessel structures. The specific printing process is as follows:

[0050] (1) Preparation of PEGNB / HAMA precursor solution: Four-arm polyethylene glycol (PEGNB) with o-nitrobenzyl group and methacrylated hyaluronic acid (HAMA) with double bond are dissolved and mixed in PBS solution to form a printing precursor solution. The mass concentration of four-arm polyethylene glycol with o-nitrobenzyl group in the precursor solution is 10%, and the mass concentration of methacrylated hyaluronic acid is 2%.

[0051] (2) A secondary bifurcation pipe model was created using Shapr3D 3D modeling software, such as... Figure 7 As shown, the secondary bifurcated tube model includes three rectangular sheet structures. The connecting area of ​​these three rectangular sheet structures uses a semi-circular structure, and a semi-elliptical notch is designed at the tangent position of the semicircle at one end to adapt to the connection with the rolled-up tubular structure. Rectangular sheet 1 is 13mm long and 5mm wide; rectangular sheet 2 is 10.4mm long and 4mm wide; and rectangular sheet 3 is 7.8mm long and 3mm wide. The major axes of rectangular sheets 1 and 2, and 2 and 3 form a 45° angle. The major axes of rectangular sheets 1 and 3 are parallel. The semi-circular connecting diameter is the length of the shorter side of the rectangle. The minor axis of the semi-elliptical notch is calculated as (outer diameter of the rolled-up tubular structure = shorter side of the rectangle) / 2π. The major axis is the length of overlap between the connecting semi-ellipse and its own rectangular sheet, and is parallel to the major axis of the rectangle. The upper and lower tangents of the semi-ellipse are parallel to the shorter side of the rectangle, and their intersection points with the semicircle are at the same horizontal level. The overall thickness of the model is 0.5mm. The 3D model is saved in STL format.

[0052] (3) Place the precursor solution into the feed tank of the DLP printer, import the secondary branching tube model into the DLP printer, and print according to the model design. The printing parameters are: light intensity 20mW / cm2, exposure time 960s, slice thickness 500μm, number of base layers 1, peel distance 6mm, lifting height 0mm, peel speed 18mm / min, lifting speed 100mm / min, peel recovery speed 180mm / min.

[0053] (4) The model is removed after overall printing. According to this embodiment, after the printed structure is photocured, the organic matter on the upper and lower surfaces generates a wettability gradient due to the reaction. When immersed in water, the swelling near the light source is greater than the swelling away from the light source, and the extended axis of the structure self-curls to form a secondary bifurcated tube structure. The secondary bifurcated tube structure is then further irradiated with ultraviolet light in the solution. Forming a closed secondary branching tube structure, such as Figure 8 As shown.

[0054] Through the model design in Examples 1-4, the formed structure can realize a hollow tubular structure with complex branches, and its variation law can be controlled according to the model design.

[0055] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. For those skilled in the art, the present invention can have various changes and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for 4D printing of complex branching vascular structures based on illumination, characterized by: The printing method comprises the following steps: (1) preparing printing raw materials: dissolving and mixing four-arm polyethylene glycol with ortho-nitrobenzyl and methyl methacrylate hyaluronic acid in PBS to obtain a 4D printing precursor solution, wherein the mass concentration of the four-arm polyethylene glycol with ortho-nitrobenzyl is 10-15%, and the mass concentration of the methyl methacrylate hyaluronic acid is 2-4%; (2) using Shapr3D three-dimensional modeling software to create a tube model of complex branched blood vessels, wherein the tube model comprises a Y-shaped tube model, a T-shaped tube model, a first-order branched tube model and a second-order branched tube model; (3) The precursor solution prepared in step (1) is placed in the DLP printer tank, and material printing is performed based on the pipe model to be printed according to the design scheme to form a pipe sheet structure, the thickness of the pipe sheet structure is 500 μm, and the printing parameters are as follows: light intensity 20 mW / cm 2 , model slice thickness 500 μm, exposure time: 960-2100 s; (4) after the model in step (3) is printed as a whole, the tube structure is taken out and completely immersed in a PBS solution, and the structure is self-crimped to form a complex branched blood vessel structure, and the complex branched blood vessel structure is subjected to secondary crosslinking under ultraviolet light in the PBS solution to form a closed complex branched blood vessel structure; the complex branched blood vessel structure comprises a Y-shaped tube, a T-shaped tube, a first-order branched tube or a second-order branched tube.

2. The 4D printing method of complex branched blood vessel structures based on illumination according to claim 1, characterized in that: The Y-shaped tube model is formed by splicing three main tube pieces, and the connection positions of the three main tube pieces are provided with semicircular link pieces of the same size, and the outer convex regions of the semicircular link pieces of the three main tube pieces are connected to each other; the T-shaped tube model is formed by splicing two main tube pieces into a T shape, wherein the main tube piece in the vertical region is provided with a semicircular link piece at the splicing position, and the main tube piece in the horizontal region is provided with a semicircular interface matching the diameter of the T-shaped tube.

3. The 4D printing method of complex branched blood vessel structures based on illumination according to claim 1, characterized in that: The first-order branched tube model is formed by splicing a main tube piece and a first-order branch tube piece, one side of the first-order branch tube piece is connected to the main tube piece, and a semicircular link piece with the same angle as the included angle between the main pipe and the first-order branch pipe of the first-order branched tube to be printed is arranged at the end of the first-order branch tube piece, a semicircular interface is arranged at the opposite side of the main tube piece, the semicircular interface is compatible with the first-order branch pipe after the first-order branch tube piece is crimped, the long diameter of the semicircular interface is equal to the length of the overlapping part of the main pipe after the first-order branch tube piece is crimped, and is parallel to the long axis of the main pipe, and the short diameter of the semicircular interface is equal to the outer diameter of the first-order branch pipe, and is perpendicular to the long axis of the main pipe; the second-order branched tube model is provided with a second-order branch tube piece on one side of the first-order branch tube piece of the first-order branched tube model, the end of the second-order branch tube piece is provided with a semicircular link piece matching the inclined angle of the second-order branch pipe, and the other side of the first-order branch tube piece is provided with a semicircular interface compatible with the second-order branch pipe after the second-order branch tube piece is crimped.

4. The 4D printing method of complex branched blood vessel structure based on illumination according to claim 1 or 2 or 3, characterized in that: The mass concentration of the four-arm polyethylene glycol with ortho-nitrobenzyl in the precursor solution in step (1) is 10%, and the mass concentration of the methyl methacrylate hyaluronic acid is 2%; the exposure time during printing in step (3) is 960s.

5. The 4D printing method of complex branched blood vessel structures based on light according to claim 1 or 2 or 3, characterized in that: The step (4) is the secondary cross-linking by ultraviolet light in PBS solution, which is irradiated by ultraviolet light for 5-6 min. The step (4) is the secondary cross-linking by ultraviolet light in PBS solution, which is irradiated by ultraviolet light for 5-6 min.

6. The method of claim 2, wherein the method is a 4D printing method of complex branched blood vessel structures based on illumination. The two main tube pieces of the T-shaped tube model are rectangular pieces, the center of the semicircular interface on one of the main tube pieces is on the same straight line as the long axis of the other main tube piece; the three main tube pieces of the Y-shaped tube model are rectangular pieces, the long axes of the three rectangular main tube pieces form an angle of 120° with each other, and the intersection points of the semicircular link pieces form a closed figure.

7. The method of claim 3, wherein the method further comprises: When the branch pipe of the pipe model is of the middle vertical type, a semicircular joint is used at the pipe piece connection, the long diameter of the semi-elliptical notch on the main pipe piece is 1 / 4 of the diameter of the branch pipe, the long diameter is perpendicular to the long axis of the main pipe, the short diameter is the outer diameter of the branch pipe, and the short diameter is parallel to the long axis of the main pipe.

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