A method for preparing tapered artificial blood vessels based on melt electrostatic direct writing

Abstract

This invention belongs to the field of polymer additive manufacturing technology and discloses a method for preparing a conical artificial blood vessel based on melt electrostatic direct writing. First, the macroscopic structural parameters of the conical artificial blood vessel are determined. Then, a fan-shaped annular side view of the conical artificial blood vessel is constructed. Within the constructed side view, a fiber deposition path curve for melt electrostatic direct writing is designed, and the control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the conical model, and the vertical movement of the print head is derived. Subsequently, control commands based on the mapping relationship drive the melt electrostatic direct writing printing equipment for printing. Finally, the printed conical biodegradable polymer skeleton is coated to obtain the conical artificial blood vessel. This invention can achieve a smoother and more continuous diameter connection with the host blood vessel, allowing blood flow to maintain a more stable velocity and pressure change trend at the junction, which is beneficial to improving the flow adaptability and sealing reliability of the anastomosis.

Description

Technical Field

[0001] This invention belongs to the field of polymer additive manufacturing technology and relates to a method for preparing tapered artificial blood vessels based on melt electrostatic direct writing. Background Technology

[0002] In modern medicine, artificial blood vessels are important medical devices, primarily used to replace or repair blood vessels damaged or defective due to disease, injury, or other causes, and have a wide range of applications. An ideal artificial blood vessel needs to possess good biocompatibility, excellent mechanical properties, and good integration with host tissues to ensure long-term patency and reduce the occurrence of complications.

[0003] Anatomical studies show that natural blood vessels in the human body (especially peripheral arteries) generally exhibit a tapered shape, with a larger proximal diameter and a gradually tapering distal diameter. However, due to limitations in geometric control and structural adaptation in traditional artificial blood vessel manufacturing processes, most artificial blood vessels used in clinical practice and research are currently straight-tube structures. Straight-tube artificial blood vessels often experience geometric mismatches when anastomosed with the tapering host vessels, leading to discontinuities in the velocity and pressure distribution of fluids in the connection region, thus deviating the flow environment at the anastomosis from physiological conditions. In contrast, tapered artificial blood vessels more closely approximate the gradual transition characteristics of natural blood vessels, allowing for a natural transition between proximal and distal diameters. This contributes to a smoother, more continuous velocity and pressure variation trend in the anastomosis region, improving overall flow adaptability and mechanical coordination. Therefore, constructing artificial blood vessels with tapering structures is of great significance for improving anastomotic performance and long-term stability.

[0004] Since the preparation method of tapered artificial blood vessels has attracted attention in recent years, in order to improve geometric adaptability, existing technologies usually use weaving and electrospinning methods to prepare tapered artificial blood vessels.

[0005] The machine-woven method mainly achieves the weaving of conical tube structures through customized looms. For example, in reference 1 (Automatic Formation Techniques of Woven Conical Vascular Graft[J]. Journal of Donghua University (English Edition), 2017, 34 (06)), a rapier prototype loom was independently modified and designed, and a software control system for the machine was established, successfully fabricating conical tube artificial blood vessels. Subsequently, reference 2 (Preparation of Conical Machine-Woven Artificial Blood Vessels with Continuously Changing Diameter and Simulation Evaluation of Blood Flow Behavior[J]. Modern Textile Technology, 2022, 30 (05)) also verified that the conical tube wall structure prepared using customized looms is relatively uniform, and the preparation process has certain feasibility and reliability. However, this method is time-consuming and it is difficult to accurately reproduce the personalized geometric parameters of complex blood vessels, especially in terms of micron-scale structural control.

[0006] Electrospinning can construct tapered stents by changing the shape of the receiving device. For example, the equipment used in reference 3 (Preparation and Performance Study of Tapered Corrugated Small-Diameter Artificial Blood Vessels [D]. Donghua University, 2012) is an electrospinning device. A tapered collecting roller was designed, and a spiral corrugated treatment device was fixed to its surface to prepare a tapered artificial blood vessel with a smooth inner wall and no blockage. However, although this method can produce nanoscale fiber structures, it lacks precise path control, leading to disordered fiber accumulation. The mechanical properties of artificial blood vessels are highly dependent on the orientation, arrangement, and interlayer structure of the fibers. Disordered accumulation prevents precise mechanical control, limiting its potential for clinical applications.

[0007] In recent years, melt electrowriting (MEW) technology, as a high-precision, solvent-free polymer additive manufacturing method, has demonstrated unique advantages in the field of vascular tissue engineering. Utilizing a high-precision CNC platform, MEW can achieve layer-by-layer controllable deposition of continuous fibers from micrometers to submicrometers, constructing three-dimensional scaffolds with highly ordered porous structures and customized macroscopic morphologies. The electrowritten scaffolds possess excellent mechanical adjustability and biocompatibility, providing a new technological pathway for the fabrication of tapered artificial blood vessels.

[0008] Currently, research on MEW-based artificial blood vessels mainly focuses on straight tube structures, while the fabrication of tapered vessels remains in the exploratory stage. For example, reference 4 (Dissolvable 3D printed PVA moulds for melt electrowriting tubular scaffolds with patient-specific geometry, Materials & Design, Volume 215, 2022) uses a custom script in Mathematica software. It first calculates the ideal pore area and fiber layup angle, then rounds the results to the nearest integer value to ensure structural integrity, generating G-code to control the rotation and translation speed of the mandrel during melt electrowriting, successfully printing a variable-diameter tubular stent. However, this method, by rounding to calculate the number of pores, is prone to geometric errors, leading to inaccurate printing. Furthermore, the lack of digital preview and visualization of the fiber path increases the risk of printing failure. It also fails to achieve seamless and smooth anastomosis with the host blood vessel, thus failing to effectively improve hemodynamic performance.

[0009] Therefore, it is of great significance to study a method for preparing conical artificial blood vessels based on melt electrostatic direct writing to solve the above problems. Summary of the Invention

[0010] The purpose of this invention is to solve the problems existing in the prior art and provide a method for preparing conical artificial blood vessels based on melt electrostatic direct writing.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] A method for fabricating a tapered artificial blood vessel based on melt electrostatic direct writing includes the following steps:

[0013] S1: Based on the anatomical structures of the proximal and distal ends of the host blood vessel to be replaced, determine the macroscopic structural parameters of the tapered artificial blood vessel, including the proximal inner diameter. distal inner diameter and the length of the tube busbar The method for determining the macroscopic structural parameters of the tapered artificial blood vessel is as follows: Medical imaging techniques (such as CT angiography or MRI angiography) are used to obtain the proximal and distal anastomotic data of the host blood vessel to be replaced, thereby determining the proximal inner diameter. and distal inner diameter (satisfy ), and spatial distance under natural physiological conditions ( ),based on The length of the tube's generatrix was calculated. ;

[0014] S2: Based on the macroscopic structural parameters determined in step S1, construct the fan-shaped annular side view of the tapered artificial blood vessel;

[0015] S3: In the side unfolded view constructed in step S2, design the fiber deposition path curve for melt electrostatic direct writing processing, and derive the control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the conical tube model and the vertical movement of the print head based on the geometric relationship.

[0016] The method for determining the fiber deposition path curve is as follows: design one or more curve segments within the fan ring, with each curve segment ending at the straight boundary on both sides of the fan ring; by applying cross-joint mapping constraints, when the fan ring is rolled into a three-dimensional conical tube, the endpoint of the curve segment ending at one boundary coincides with the starting point of the curve segment ending at the other boundary, and has a consistent three-dimensional spatial tangent direction at the point of coincidence, thereby forming a continuous and smooth fiber path in three-dimensional space.

[0017] S4: Based on the mapping relationship derived in step S3, generate G-code or equivalent control command to drive the melt electrostatic direct writing printing device to print and obtain a conical biodegradable polymer skeleton with a preset porous structure.

[0018] S5: The tapered biodegradable polymer skeleton with a preset porous structure obtained in step S4 is coated to obtain a tapered artificial blood vessel.

[0019] As a preferred technical solution:

[0020] As described above, in the method for fabricating a tapered artificial blood vessel based on melt electrostatic direct writing, in step S1, the length of the tube generatrix... The method for determining this is as follows: obtain the spatial distance between the proximal and distal anastomoses of the host blood vessel to be replaced under natural physiological conditions. Through formula The length of the tube's generatrix was calculated. ,in The redundant length, used to maintain the natural curvature of the artificial blood vessel after anastomosis and avoid local tension concentration, was determined through finite element simulation analysis of the physiological curvature deformation of the host blood vessel. .

[0021] The above describes a method for preparing a conical artificial blood vessel based on melt electrostatic direct writing. and The percentage ratio (i.e., redundancy) is 5-15% to ensure uniform tension distribution during the operation and to compensate for the elastic elongation of the vessel wall.

[0022] In the above-described method for fabricating a tapered artificial blood vessel based on melt electrostatic direct writing, in step S2, the small radius of the fan ring... Large radius and central angle The proximal inner diameter of the tapered artificial blood vessel distal inner diameter and the length of the tube busbar Determined through geometric relationships;

[0023] ;

[0024] ;

[0025] .

[0026] As described above, in the method for preparing a conical artificial blood vessel based on melt electrostatic direct writing, the cross-slit mapping constraint in step S3 is expressed in the fan-ring side unfolded diagram as follows: For a pair of boundary points P1 and P2 that are expected to coincide in three-dimensional space, where P1 is located on one side boundary and P2 is located on the other side boundary, the following conditions must be met: a) Point P1 and point P2 have the same radial coordinate R; b) The tangent vector of the curve at point P1 and the tangent vector of the curve at point P2 have the same deflection angle relative to the corresponding boundary in the fan-ring side unfolded diagram.

[0027] As described above, a method for fabricating tapered artificial blood vessels based on melt electrostatic direct writing discretizes the fiber deposition path curve into a point sequence, where each point in the point sequence is represented by polar coordinates. , ) indicates that among them Radial coordinates, It uses polar coordinates and introduces a cumulative lap count correction parameter that is updated synchronously with the point series. This is used to record and correct the history of fiber deposition path crossing the seam; the specific control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the conical tube model, and the vertical movement of the print head is as follows:

[0028] Axial position coordinates: ;

[0029] Circumferential rotation angle: ;

[0030] Z-axis position coordinates: ;

[0031] in, The semi-cone angle of the conical artificial blood vessel satisfies the following conditions. ; This is a preset constant distance between the print head and the axis of rotation of the conical tube model.

[0032] The above point list and parameters The generation rules are as follows:

[0033] (1) Initialization: Using the center of the fan ring as the pole and the straight boundary on one side as the polar axis, uniformly sample the path curve to generate an initial point sequence. , ), and set =0;

[0034] (2) Sequence Update: The initial point sequence is traversed sequentially, and the sequence is updated in real time based on the path's crossing behavior relative to the upper and lower boundaries of the fan ring. The value of is: when the sampling point sequence indicates that the path crosses the upper boundary of the fan ring, let . = +1; When the sampling point sequence indicates that the path enters from the lower boundary of the fan ring, let If there is no time travel, then let ;

[0035] (3) Trajectory generation: based on the updated The polar coordinates of each point are corrected to form the final trajectory point sequence used to control the platform's motion. ,in, The central angle of the fan ring;

[0036] Final trajectory point list As input, based on the above geometric mapping relationship, three-axis linkage control commands that drive the printing platform and the conical tube model to move in a coordinated manner are calculated and generated synchronously. .

[0037] The derivation of the above mapping relationship is as follows:

[0038] (a) The tapered artificial blood vessel is a truncated cone (i.e., a frustum), and its extended generatrices intersect at the apex. The center of the base of the frustum is The angle between the generatrix and the central axis is a semi-cone angle. .by Point is the origin. Establish a three-dimensional Cartesian coordinate system with the y-axis as the axis. During the melt electrolysis process, the print head is constantly... On a plane. Therefore, in the initial state, the boundary of the top of the frustum is... The upper intersection point A of the planes is the starting point for printing.

[0039] (b) along A unfolds the solid cone to obtain a fan-shaped lateral surface development. The point is the center of the circle. Establish a polar coordinate system with A as the polar axis. Within the unfolded side view, take any point... Its coordinates are In the 3D diagram, through Draw a circular cross-section parallel to the bottom surface, with its center at point A. The circular cross-section intersects the generatrix containing point A. Dot, dot The corresponding polar coordinates are .

[0040] (c) When printed to At point, The point should be rotated to It lies in a plane, specifically on the positive z-axis. Within a right triangle... middle, and .therefore, The three-dimensional coordinates of the point are Since the printhead maintains a constant distance D from the receiver, the coordinates of the printhead at this time are... .

[0041] (d) Let arc The length is s. At the center of the circle... Within the cross section, the arc The radius is The included central angle is Therefore, arc Length is In the side unfolded diagram, the arc The radius is The corresponding central angle is Therefore, arc Length is Combine two arcs The length formula can be obtained as follows: .

[0042] The specific printing process in step S4 of the above-described method for fabricating a tapered artificial blood vessel based on melt electrostatic direct writing is as follows:

[0043] S41: Based on the macroscopic structural parameters of the tapered artificial blood vessel, a tapered sacrificial substrate is printed using a water-soluble support material through fused deposition modeling (FDM) technology.

[0044] S42: The sacrificial substrate obtained in step S41 is used as a collection device and installed on the rotating platform of the melt electrostatic direct writing equipment to perform fiber printing deposition and obtain a polymer skeleton covered thereon.

[0045] S43: After printing, the polymer skeleton with the sacrificial substrate is placed in water to dissolve the sacrificial substrate, thereby obtaining the conical biodegradable polymer skeleton without damage.

[0046] As described above, in the method for preparing a conical artificial blood vessel based on melt electrostatic direct writing, the water-soluble support material is polyvinyl alcohol; the material used for melt electrostatic direct writing is a biodegradable thermoplastic polymer, specifically including polycaprolactone, polylactic acid, or copolymers thereof.

[0047] As described above, in the method for preparing a conical artificial blood vessel based on melt electrostatic direct writing, the coating process in step S5 specifically involves: immersing the conical biodegradable polymer skeleton in a biopolymer solution, followed by curing treatment to form a dense, leak-proof functional layer on its surface and within its pores.

[0048] The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing as described above uses a biopolymer solution, which is a gelatin solution, collagen solution, silk fibroin solution, chitosan solution, or human basement membrane extract (such as HuBiogel™) solution. The concentration of the biopolymer solution is 0.1~15wt%. Preferably, 0.1~0.5wt% heparin can be added to enhance anticoagulant properties.

[0049] The curing process can be either chemical crosslinking or photocrosslinking. The crosslinking agent used for chemical crosslinking is glutaraldehyde, genipin, or carbodiimide, while the photoinitiator used for photocrosslinking is Irgacure 2959 or LAP.

[0050] Beneficial effects:

[0051] (1) This invention is based on the inner diameter of the proximal and distal ends of the host blood vessel ( , ) and physiological span ( Precisely design the geometric parameters of the tapered tube and introduce 5-15% redundancy. This structure enables a smoother and more continuous diameter connection with the host blood vessels, reducing flow disturbances caused by sudden expansion or contraction. This allows blood flow to maintain a more stable velocity and pressure change trend at the junction, which is beneficial to improving the flow adaptability and sealing reliability of the anastomosis.

[0052] (2) The present invention uses melt electrostatic direct writing technology and thermoplastic biodegradable polymers as raw materials. It does not require the use of organic solvents, thus fundamentally avoiding the solvent residue toxicity problem commonly found in electrospinning processes, and improving the biosafety and long-term in vivo compatibility of the grafts.

[0053] (3) This invention unfolds the conical tube surface into a two-dimensional fan-shaped plane, performs parametric design of the fiber deposition path on this plane, and accurately converts the two-dimensional curve into a continuous and smooth fiber trajectory in three-dimensional space through strict geometric mapping relationships. This strategy significantly reduces the programming complexity of multi-axis linkage control, while ensuring the path fidelity and structural repeatability of micron-level fiber deposition.

[0054] (4) The artificial blood vessels prepared by the present invention can achieve seamless and smooth anastomosis with the host blood vessels, effectively improve hemodynamic performance, reduce complications, and its path planning and design method is intuitive and accurate, providing a new strategy for additive manufacturing of complex geometric structures. Attached Figure Description

[0055] Figure 1 This is a schematic diagram of the path generation principle of the fan-shaped annular side view unfolded in Embodiment 1 of the present invention;

[0056] Figure 2 This is a three-dimensional path diagram of the tapered artificial vascular stent formed in step S3 of embodiment 1 of the present invention;

[0057] Figure 3 This is a schematic diagram of the conical biodegradable polymer skeleton with a preset porous structure prepared in Example 1 of the present invention;

[0058] Figure 4 This is a schematic diagram comparing the blood flow velocity distribution across the axial sections of the conical and straight artificial blood vessels in Model 1 and Model 2 of this invention.

[0059] Figure 5 This is a schematic diagram comparing the blood flow velocity distribution along the central axis of the conical and straight artificial blood vessels in Model 1 and Model 2 of this invention.

[0060] Figure 6 This is a schematic diagram comparing the blood pressure distribution across the axial sections of the conical and straight artificial blood vessels in Model 1 and Model 2 of this invention.

[0061] Figure 7 This is a schematic diagram comparing the blood pressure distribution along the central axis of the conical and straight artificial blood vessels in Model 1 and Model 2 of this invention.

[0062] Figure 8 This is a schematic diagram of the path generation principle of the fan-shaped side unfolded diagram in Embodiment 2 of the present invention; in the figure, the black arrows represent the final fiber path, the black solid lines represent the boundary of the unfolded diagram, and the black dashed lines represent the expansion arc and the original path that exceeds the boundary.

[0063] Figure 9 This is a side view of the tapered artificial blood vessel formed in step S3 of embodiment 2 of the present invention.

[0064] Figure 10 This is a three-dimensional schematic diagram of the tapered artificial vascular stent formed in step S3 of embodiment 2 of the present invention. Detailed Implementation

[0065] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0066] A method for fabricating a tapered artificial blood vessel based on melt electrostatic direct writing, comprising the following steps:

[0067] S1: Based on the anatomical structures of the proximal and distal ends of the host blood vessel to be replaced, determine the macroscopic structural parameters of the tapered artificial blood vessel, including the proximal inner diameter. distal inner diameter and the length of the tube busbar ;

[0068] Pipe busbar length The method for determining this is as follows: obtain the spatial distance between the proximal and distal anastomoses of the host blood vessel to be replaced under natural physiological conditions. Through formula The length of the tube's generatrix was calculated. ,in It is a redundant length, and , and The percentage ratio is 5-15%;

[0069] S2: Based on the macroscopic structural parameters determined in step S1, construct the fan-shaped annular lateral view of the tapered artificial blood vessel; wherein, the small radius of the fan-shaped annular... Large radius and central angle The proximal inner diameter of the tapered artificial blood vessel distal inner diameter and the length of the tube busbar Its smaller radius is determined by geometric relationships. Large radius and central angle The calculation formula is as follows:

[0070] ;

[0071] ;

[0072] ;

[0073] S3: In the side unfolded view constructed in step S2, design the fiber deposition path curve for melt electrostatic direct writing processing, and derive the control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the conical tube model and the vertical movement of the print head.

[0074] S31: Within the side unfolded view constructed in step S2, design the fiber deposition path curve for melt electrostatic direct writing processing. The method for determining the fiber deposition path curve is as follows:

[0075] First, design one or more curve segments within the fan ring. Each curve segment terminates at both ends of the straight line boundaries on both sides of the fan ring. Then, by applying a cross-joint mapping constraint, when the fan ring is rolled into a three-dimensional conical tube, the endpoint of the curve segment terminating at one boundary coincides with the starting point of the curve segment terminating at the other boundary, and they have a consistent three-dimensional tangent direction at the point of coincidence. The cross-joint mapping constraint is expressed in the fan ring side unfolded diagram as follows: For a pair of boundary points P1 and P2 that are expected to coincide in three-dimensional space, where P1 is located on one boundary and P2 is located on the other boundary, the following conditions must be met: a) Points P1 and P2 have the same radial coordinate R; b) The tangent vector of the curve at point P1 and the tangent vector of the curve at point P2 have the same deflection angle relative to the corresponding boundary in the fan ring side unfolded diagram.

[0076] S32: Discretize the fiber deposition path curve determined above into a point sequence, and use polar coordinates for each point in the point sequence. , ) indicates that among them Radial coordinates, It uses polar coordinates and introduces a cumulative lap count correction parameter that is updated synchronously with the point series. This is used to record and correct the history of fiber deposition paths crossing joints;

[0077] The above point list and parameters The generation rules are as follows:

[0078] (1) Initialization: Using the center of the fan ring as the pole and the straight boundary on one side as the polar axis, uniformly sample the path curve to generate an initial point sequence. , ), and set =0;

[0079] (2) Sequence Update: The initial point sequence is traversed sequentially, and the sequence is updated in real time based on the path's crossing behavior relative to the upper and lower boundaries of the fan ring. The value of is: when the sampling point sequence indicates that the path crosses the upper boundary of the fan ring, let . = +1; When the sampling point sequence indicates that the path enters from the lower boundary of the fan ring, let If there is no time travel, then let ;

[0080] (3) Trajectory generation: based on the updated The polar coordinates of each point are corrected to form the final trajectory point sequence used to control the platform's motion. ,in, The central angle of the fan ring;

[0081] S33: Derive the control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the tapered tube model, and the vertical movement of the print head, specifically:

[0082] Axial position coordinates: ;

[0083] Circumferential rotation angle: ;

[0084] Z-axis position coordinates: ;

[0085] in, The semi-cone angle of the conical artificial blood vessel satisfies the following conditions. ; This is a preset constant distance between the print head and the axis of rotation of the conical tube model;

[0086] S4: Obtain a conical biodegradable polymer skeleton with a preset porous structure;

[0087] S41: Based on the macroscopic structural parameters of the tapered artificial blood vessel, a tapered sacrificial substrate is printed using fused deposition modeling (FDM) technology with a water-soluble support material; wherein, the water-soluble support material is polyvinyl alcohol;

[0088] S42: The sacrificial substrate obtained in step S41 is used as a collection device and installed on the rotating platform of the melt electrostatic direct writing equipment. Then, based on the mapping relationship derived in step S3, a G-code or equivalent control command is generated to drive the melt electrostatic direct writing printing equipment to print and deposit fibers, thereby obtaining a polymer skeleton covered on it. The material used in melt electrostatic direct writing is a biodegradable thermoplastic polymer (polycaprolactone, polylactic acid, or copolymers thereof).

[0089] S43: After printing, the polymer skeleton with the sacrificial substrate is placed in water to dissolve the sacrificial substrate, thereby obtaining a conical biodegradable polymer skeleton with a preset porous structure without damage.

[0090] S5: The conical biodegradable polymer skeleton with a preset porous structure obtained in step S4 is immersed in a biopolymer solution (gelatin solution, collagen solution, silk fibroin solution, chitosan solution, or human basement membrane extract solution) with a concentration of 0.1~15wt% for 24h, followed by curing treatment to form a dense, leak-proof functional layer on its surface and in the pores. After washing with phosphate buffered saline (PBS solution) 3~5 times to remove residual solution, it is freeze-dried at -50°C for 24h to maintain the uniformity of the coating in the pores, thus obtaining a conical artificial blood vessel. The curing treatment method is chemical crosslinking or photocrosslinking. The crosslinking agent used for chemical crosslinking is glutaraldehyde, genipin, or carbodiimide, the chemical crosslinking temperature is 25~37°C, and the chemical crosslinking time is 2~6h. The photoinitiator used for photocrosslinking is Irgacure 2959 or LAP.

[0091] To verify the feasibility of the above-mentioned method for fabricating conical artificial blood vessels based on melt electrostatic direct writing, we will now use the above method to fabricate a conical artificial blood vessel with a diamond-shaped grid pattern on the side as an example for illustration, as follows:

[0092] Example 1

[0093] The conical artificial blood vessel was prepared using the above-mentioned method based on melt electrostatic direct writing, and the specific steps are as follows:

[0094] S1: Obtain anatomical data of the femoral artery to be replaced using CT angiography to determine the proximal diameter of the tapered artificial blood vessel. =7.5mm, distal inner diameter =8.75mm, the straight-line spatial distance between the proximal and distal anastomoses of the host blood vessel to be replaced under natural physiological conditions. =54.53mm, according to surgical guidelines, a redundancy length is set. =5.453mm, therefore the length of the tube's generatrix is... =60mm;

[0095] S2: Based on the macroscopic structural parameters determined in step S1, the geometric parameters of the fan-shaped annular side view of the tapered artificial blood vessel are calculated as follows: the small radius of the fan-shaped annular side view. It has a radius of 360.0 mm. It is 420mm, and the central angle is... It is 0.0654 rad;

[0096] S3: In step S31, first write Python code to generate a continuous, non-jumping fiber deposition path, draw a diamond-shaped mesh, and discretize the mesh pattern, as follows:

[0097] (I) Establishing a polar coordinate system and initial state: With the center of the fan ring as the pole O and the straight boundary on one side (corresponding to the generatrix joint of the three-dimensional conical tube) as the polar axis, establish a polar coordinate system. ;

[0098] (II) Define path generation rules: The path starts from the starting point on the inner arc. = Starting from, alternately connecting to the outer and inner arcs, where the polar angle increment for each target point is... All When a path intersects a boundary, for a pair of boundary points P1 and P2 that are expected to coincide in three-dimensional space, where P1 is located on one side of the boundary and P2 is located on the other side of the boundary, the following conditions must be met during the design:

[0099] a) Points P1 and P2 have the same radial coordinates ;

[0100] b) The tangent vector of the curve at point P1 and the tangent vector of the curve at point P2 have the same deflection angle relative to the boundary in the fan-ring unfolded diagram; such as Figure 1 As shown, represented in polar coordinates, from point... Start from point and draw a straight line to point. Due to line segments Intersects with the upper boundary at point The path crosses the boundary, therefore the line segment... Around the center Rotate clockwise by one angle line segment This is the rotated path, with the midpoint... and Separately with points and With the same radial coordinates, the path continues from point... Departure point Path after crossing The angle between the upper and lower boundaries is equal to the path before crossing. The angle with the upper boundary; then from the point Start from point d and draw a straight line to point d. Since the straight line intersects the upper boundary at point . The path crosses the boundary, therefore the line segment... Around the center Rotate clockwise by one angle line segment This is the rotated path, with the midpoint... and Separately with points and With the same radial coordinates, the path continues from point... Departure point Path after crossing The angle between the upper and lower boundaries is equal to the path before crossing. The angle between the line segment and the upper boundary, due to the line segment In If the segment exceeds the boundary, the same method is used to... Adjusted to Then, continue drawing. Repeat this process to obtain the path. ;

[0101] When the endpoint of the line segment falls on the inner arc and That is, the endpoint of the line segment is When the drawing stops, the final endpoint and starting point of the continuous path are drawn after the path diagram is rolled into a 3D graphic. coincide;

[0102] In step S32, uniform sampling is performed at fixed intervals of 0.01 units to generate a series of discrete points that form the initial point sequence. ;

[0103] The three-dimensional path of the tapered artificial vascular stent formed according to step S3 is as follows: Figure 2 As shown;

[0104] S4: In step S41, a conical sacrificial substrate is printed using polyvinyl alcohol as a water-soluble support material. =7.5mm, =8.75mm, busbar length =60mm);

[0105] In step S42, polycaprolactone (PCL) is used as the printing material. Based on the control commands generated in step S3, the rotating platform and the nozzle are driven to perform three-axis linkage printing to obtain the polymer skeleton covered on it. The parameters of the melt electrostatic direct writing equipment are set as follows: heating jacket temperature 70°C, applied voltage 4.5kV, nozzle-to-collector distance 2.59mm, ambient temperature 22°C, relative humidity 34%, printing speed 300mm / min, and the system is allowed to stabilize for 0.8 hours before printing to ensure jet stability.

[0106] In step S43, the polymer skeleton with the sacrificial substrate is placed in water and sonicated for 2 hours to dissolve the sacrificial substrate, thereby non-destructively separating and obtaining a conical biodegradable polymer skeleton with a pre-defined porous structure (e.g., Figure 3 (as shown)

[0107] S5: The tapered biodegradable polymer skeleton with a preset porous structure obtained in step S4 is immersed in a 1wt% HuBiogel™ solution (composed of phosphate buffer at pH 7.4 and HuBiogel™ from LifeNet Health) for 24 hours, followed by holding at 37°C for 2 hours to promote HuBiogel gelation. Then, the immersed polymer skeleton is immersed in a 200mM genipin solution (composed of genipin powder and ethanol) for 24 hours to crosslink and cure it. After forming a dense, leak-proof functional layer on its surface and in the pores, it is washed 5 times with a phosphate buffer solution at pH 7.4 to remove residual solution, and then freeze-dried at -50°C for 24 hours to maintain the uniformity of the coating in the pores, thus obtaining a tapered artificial blood vessel.

[0108] To further verify the above-mentioned method for fabricating conical artificial blood vessels based on melt electrostatic direct writing, a conical artificial blood vessel with a surface of non-uniform spiral rhombic fiber mesh was fabricated, as detailed below:

[0109] Example 2

[0110] A method for fabricating a conical artificial blood vessel based on melt electrostatic direct writing is basically the same as in Example 1, except that: the fan-shaped annular side view of the conical artificial blood vessel calculated in step S2 is shown below. Figure 8 As shown, its geometric parameters are: the small radius of the fan ring. It has a radius of 360mm. It is 420mm, and the central angle is... It is 0.0654 rad, and its polar angle change rate ω = 0.002;

[0111] The side view of the tapered artificial vascular stent formed in step S3 is shown below. Figure 9 As shown, its three-dimensional image is as follows: Figure 10 As shown;

[0112] In the fiber deposition path planning of this embodiment, a fixed polar angle increment is no longer used. Instead of alternating straight line segments, it introduces the polar angle change rate ω, and determines the polar radius based on the polar angle change rate ω and the current position. The polar coordinates of each point on the curve are calculated in real time, and then the points are connected in sequence.

[0113] like Figure 8 As shown, represented in polar coordinates, from point... Start by using the formula Calculate the position of each point on the curve and plot the curve to the point. ,in The order of values ​​is Increment to Due to the curve Intersects with the upper boundary at point The path crosses the boundary, therefore the line segment... Around the center Rotate clockwise by one angle The rotated path is obtained. , midpoint and Separately with points and c Having the same polar radius, the path continues from point Departure point Path after crossing The angle between the upper and lower boundaries is equal to the path before crossing. The angle between the point and the upper boundary. Then, from the point... Start by using the formula Calculate the position of each point on the curve and plot the curve to the point. ,in The order of values ​​is Decrease to Due to the curve Intersects with the upper boundary at point The path crosses the boundary, therefore the line segment... Around the center Rotate clockwise by one angle The rotated path is obtained. , midpoint and Separately with points and With the same radial coordinates, the path continues from point... Departure point Path after crossing The angle between the upper and lower boundaries is equal to the path before crossing. The angle with the upper boundary, due to Intersects the boundary line at point Therefore, the line segment After the change of direction, it was adjusted to And so on, to obtain the path. ;

[0114] Each of the above-generated deposition trajectories is a curve with continuously changing curvature, which makes the radial angle of the rhombus in the conical skeleton after winding change in a gradient along the axial direction. Specifically, the radial angle of the rhombus gradually increases from the proximal end to the distal end, thereby achieving gradient regulation of vascular compliance. This demonstrates the customizability and good biomimetic ability of melt electrowriting technology in personalized medical scenarios.

[0115] As can be seen from the above, by adjusting the bending coefficient, the present invention can achieve controllable adjustment of the local pore structure, fiber orientation and mechanical properties of the stent, which fully demonstrates the high degree of freedom, high repeatability and rapid response capability of melt electrowriting technology in personalized medical scenarios.

[0116] Fluid dynamics simulation analysis of tapered and straight artificial blood vessels was performed using the finite element analysis software COMSOL Multiphysics. The analysis process is as follows:

[0117] (1) Establish Model 1 and Model 2;

[0118] Model 1: Composed of three conical blood vessels, each 50mm high, from bottom to top: upstream vessel, conical artificial blood vessel prepared in Example 1, and downstream vessel; the upstream vessel has a bottom diameter of 10mm and a top diameter of 8mm; the conical artificial blood vessel prepared in Example 1 has a bottom diameter of 8mm and a top diameter of 7mm; the downstream vessel has a bottom diameter of 7mm and a top diameter of 6.8mm.

[0119] Model 2: Basically the same as Model 1, the only difference is that the tapered artificial blood vessel is replaced with a straight artificial blood vessel with a diameter of 8mm, and a chamfer is created at the connection between the straight artificial blood vessel and the downstream blood vessel to achieve a smooth connection;

[0120] (2) The steady-state study of blood was carried out using the "turbulent, k-ω" physical field for Model 1 and Model 2 respectively. The blood inlet was set as the large diameter end of the upstream blood vessel, and the blood flow velocity at the inlet was set to 0.2 m / s. Then, based on the calculated results, the velocity and pressure distribution maps were drawn based on the surface x=0 and the cross section of the blood vessel, and the one-dimensional distribution maps of pressure and velocity were drawn based on the central axis.

[0121] The two models were simulated using the finite element analysis software COMSOL Multiphysics, and the results are as follows: Figures 4-7 As shown, comparative studies of the results revealed that in Model 1, with the use of a tapered artificial blood vessel, the pressure gradient and velocity changes along the central axis exhibited a smooth transition characteristic; while in Model 2, significant pressure and velocity abrupt changes were observed, particularly at the connection between the artificial blood vessel and the downstream vessel. Therefore, this invention, by introducing a support structure with a specific geometric shape into the artificial blood vessel wall, enables more stable regulation of the velocity and pressure fields of blood flow within the cavity.

[0122] Simulation results from Model 2 show that, under the same flow conditions, the velocity along the axis within the structure of this invention exhibits a more continuous and smoother trend, without abrupt changes or significant gradient concentration; the pressure distribution along the flow path is also more uniform, with stable pressure drop characteristics. The stability of the velocity and pressure fields implies smoother blood flow within the lumen, which helps reduce stress concentration in the vessel wall caused by sudden changes in local shear force. In long-term implantation, this gentler flow environment can reduce the inducing factors of intimal hyperplasia, thereby improving the patency and long-term stability of the artificial blood vessel. Simultaneously, the introduction of structured support improves the deformation resistance of the artificial blood vessel under internal and external pressure, keeping the lumen closer to the designed circular cross-section, which helps maintain a stable blood flow channel. In summary, this invention does not rely on complex fluid disturbance suppression mechanisms; through only a reasonable inner wall structure design, it can achieve a more stable velocity distribution, a more uniform pressure gradient, and a more reliable mechanical support effect, thereby comprehensively improving the fluid performance and structural stability of the artificial blood vessel.

Claims

1. A method for preparing a conical artificial blood vessel based on melt electrostatic direct writing, characterized in that... Includes the following steps: S1: Based on the anatomical structures of the proximal and distal ends of the host blood vessel to be replaced, determine the macroscopic structural parameters of the tapered artificial blood vessel, including the proximal inner diameter. distal inner diameter and the length of the tube busbar ; S2: Based on the macroscopic structural parameters determined in step S1, construct the fan-shaped annular side view of the tapered artificial blood vessel; S3: In the side unfolded view constructed in step S2, design the fiber deposition path curve for melt electrostatic direct writing processing, and derive the control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the conical tube model and the vertical movement of the print head. The method for determining the fiber deposition path curve is as follows: design one or more curve segments within the fan ring, with each curve segment ending at the straight boundary on both sides of the fan ring; by applying cross-joint mapping constraints, when the fan ring is rolled into a three-dimensional conical tube, the endpoint of the curve segment ending at one boundary coincides with the starting point of the curve segment ending at the other boundary, and they have a consistent three-dimensional spatial tangent direction at the point of coincidence. The cross-joint mapping constraint in the fan-ring side unfolded diagram is as follows: For a pair of boundary points P1 and P2 that are expected to coincide in three-dimensional space, where P1 is located on one side boundary and P2 is located on the other side boundary, the following conditions must be met: a) Point P1 and point P2 have the same radial coordinate R; b) The tangent vector of the curve at point P1 and the tangent vector of the curve at point P2 have the same deflection angle relative to the corresponding boundary in the fan-ring side unfolded diagram. The fiber deposition path curve is discretized into a point sequence, and each point in the sequence is represented by polar coordinates. , ) indicates that among them Radial coordinates, Using polar coordinates, the specific control mapping relationship between the fiber deposition path curve and the axial movement of the printing platform, the circumferential rotation of the conical tube model, and the vertical movement of the print head is as follows: Axial position coordinates: ; Circumferential rotation angle: ; Z-axis position coordinates: ; in, The semi-cone angle of the conical artificial blood vessel satisfies the following conditions. ; This is a preset constant distance between the print head and the axis of rotation of the conical tube model; S4: Based on the mapping relationship derived in step S3, generate G-code or equivalent control command to drive the melt electrostatic direct writing printing device to print and obtain a conical biodegradable polymer skeleton with a preset porous structure. S5: The tapered biodegradable polymer skeleton with a preset porous structure obtained in step S4 is coated to obtain a tapered artificial blood vessel.

2. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 1, characterized in that, In step S1, the length of the tube busbar The method for determining this is as follows: obtain the spatial distance between the proximal and distal anastomoses of the host blood vessel to be replaced under natural physiological conditions. Through formula The length of the tube's generatrix was calculated. ,in It is a redundant length, and .

3. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 2, characterized in that, and The percentage ratio is 5-15%.

4. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 1, characterized in that, In step S2, the small radius of the fan ring Large radius and central angle The proximal inner diameter of the tapered artificial blood vessel distal inner diameter and the length of the tube busbar Determined through geometric relationships; ； ； 。 5. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 1, characterized in that, The specific printing process in step S4 is as follows: S41: Based on the macroscopic structural parameters of the tapered artificial blood vessel, a tapered sacrificial substrate is printed using a water-soluble support material through fused deposition modeling technology. S42: The sacrificial substrate obtained in step S41 is used as a collection device and installed on the rotating platform of the melt electrostatic direct writing equipment to perform fiber printing deposition and obtain a polymer skeleton covered thereon. S43: After printing, the polymer skeleton with the sacrificial substrate is placed in water to dissolve the sacrificial substrate, thereby obtaining the conical biodegradable polymer skeleton without damage.

6. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 5, characterized in that, The water-soluble support material is polyvinyl alcohol; The material used for melt electrostatic direct writing is a biodegradable thermoplastic polymer.

7. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 1, characterized in that, The coating process in step S5 specifically involves immersing a conical biodegradable polymer skeleton in a biopolymer solution, followed by curing to form a leak-proof functional layer on its surface and within its pores.

8. The method for preparing a conical artificial blood vessel based on melt electrostatic direct writing according to claim 7, characterized in that, The biopolymer solution is a gelatin solution, collagen solution, silk fibroin solution, chitosan solution, or human basement membrane extract solution, with a concentration of 0.1~15wt%. The curing process is either chemical crosslinking or photocrosslinking.

Images