4D printing technology-based PFO plugging device and preparation method thereof

Abstract

The invention belongs to the field of medical instruments, and particularly relates to a PFO plugging device based on a 4D printing technology and a preparation method of the PFO plugging device. The PFO plugging device comprises a main body structure. The main body structure is integrally formed in a 4D printing mode. The main body structure comprises a plurality of special-shaped ligaments, the ends of the ligaments intersect on the axis of the main body structure, and all the ligaments are arranged around the axis of the main body structure in an annular array mode. The preparation method comprises the steps of preparation of raw materials, modeling design of the PFO plugging device, 4D printing forming and connection of a main body structure and the flow blocking film. The main body structure is integrally formed through the 4D printing technology, the main body structure is high in supporting force and clamps a primary septum and a secondary septum, effective plugging is formed, the PFO plugging device can be individually formed through 4D printing according to the actual situation of a patient, the size matching degree of the PFO plugging device and the size of an affected part is high, and postoperative effective plugging is good; the stable shape of the clamped tissue is guaranteed, and the problems of tissue abrasion and long-term tissue perforation are solved while the device complies with heart movement and atrial septum swing.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical devices, and in particular relates to a PFO occluder based on 4D printing technology and a preparation method thereof. Background Art

[0002] The foramen ovale is an important structure of the heart during the embryonic period. Under normal circumstances, the foramen ovale should have been closed after the child is born. If the foramen ovale is not closed, it can be determined as a congenital heart disease. Patent foramen ovale (PFO) is a clear risk factor for cardioembolic stroke. Once it occurs, it will cause the mixing of arteries and veins, resulting in symptoms such as cyanosis and cerebral hypoxia. There are two ways to treat patent foramen ovale. One is the traditional foramen ovale closure under extracorporeal circulation, and the second is minimally invasive foramen ovale occlusion. Minimally invasive foramen ovale occlusion is performed by puncturing the femoral vein and leaving a delivery tube. All operations are performed through the delivery tube. The guide wire and catheter are placed in the right atrium along the delivery tube and positioned at the location of the foramen ovale. Then, the foramen ovale is passed from the right atrium to the left atrium through the foramen ovale. The catheter is withdrawn but the guide wire is retained to establish a surgical channel, and the foramen ovale occluder is delivered to the defect site through the delivery tube and the guide wire. Compared with traditional foramen ovale closure under extracorporeal circulation, minimally invasive foramen ovale closure has the advantages of small incision, short recovery time and good effect.

[0003] The main stent of the foramen ovale occluder currently used in clinical practice is woven from nickel-titanium alloy wire, which is soft to the touch, highly plastic, and has good shape memory and biocompatibility. However, after nickel-titanium alloy is implanted in the body, corrosion or abrasion is inevitable, which will cause the slow release of nickel ions. Patients may also be allergic to nickel-titanium alloy, and the nickel-titanium alloy occluder may not be the same size as the heart defect and fall off during use.

[0004] Therefore, it is necessary to provide an improved technical solution to address the above-mentioned deficiencies in the prior art. Summary of the invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a PFO occluder based on 4D printing technology and a preparation method thereof. The PFO occluder conforms to the "J"-type stress-strain mechanical characteristics of biological tissues / organs, conforms to the movement of cardiac structure, and ensures the stability of the clamped tissue morphology; the preparation method adopts 4D printing technology to integrate the occluder frame, has strong supporting force, and can be 4D printed according to the actual situation of the patient (transthoracic cardiac ultrasound TTE), Personalized forming of PFO occluder.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A PFO occluder based on 4D printing technology, comprising a main structure and a flow-blocking membrane wrapped outside the main structure, wherein the main structure comprises a first disc-shaped body, a second disc-shaped body, a waist and a connector, wherein the first disc-shaped body and the second disc-shaped body are connected through the waist, the connector is connected to the center of the outer end surface of the second disc-shaped body, and the connector is used to connect to a guide wire delivered externally;

[0008] The main structure is integrally formed by 4D printing; the main structure includes a plurality of special-shaped ligaments, the ends of each ligament intersect on the axis of the main structure, and all the ligaments are arranged in a circular array around the axis of the main structure; the ligament includes a first straight segment, a first spiral segment, a mid-waist straight segment, a second spiral segment, and a second straight segment connected in sequence; the first straight segments and the first spiral segments of all ligaments constitute a first disc-shaped body, the mid-waist straight segments of all ligaments constitute the waist of the main structure, and the second spiral segments and the second straight segments of all ligaments constitute a second disc-shaped body.

[0009] Furthermore, the included angle between the projections of the first straight line segment and the second straight line segment of each ligament on the perpendicular plane between the two is 60° to 65°, and the number of the ligaments is 4 to 10.

[0010] Furthermore, the inner ends of all the first straight line segments share a common end, and the outer ends extend radially and uniformly; the inner ends of all the second straight line segments share a common end, and the outer ends extend radially and uniformly; and the first spiral segment and the second spiral segment have the same rotation direction.

[0011] Furthermore, the PFO occluder based on 4D printing technology also includes sutures, through which the main structure and the flow-blocking membrane are connected; the flow-blocking membrane is a fiber membrane with a nano-microstructure having cell growth factors adhered to the surface.

[0012] Furthermore, the flow-blocking membrane at the waist position is provided with a coating, and the coating component is urokinase or reteplase.

[0013] Furthermore, the diameter of the ligament is 0.7 mm to 0.8 mm, the diameter of the first disc-shaped body is 15 mm to 17 mm, and the diameter of the second disc-shaped body is 19 mm to 21 mm.

[0014] The present invention also proposes a method for preparing the aforementioned PFO occluder based on 4D printing technology, comprising the following steps:

[0015] S1. Preparation of raw materials: melt-blending polylactic acid and polyethylene glycol, and preparing filaments by melt extrusion;

[0016] S2. PFO occluder shape design: Based on the wave-shaped bionic design concept, the main structure is designed using 3D drawing software; the first reference plane corresponding to the first disc-shaped body is constructed, and the first curve is drawn using the "artistic spline" command as the first straight line segment and the first spiral segment space projection structure curve; similarly, the second reference plane corresponding to the second disc-shaped body is constructed, and the second curve is drawn using the "artistic spline" command as the second straight line segment and the second spiral segment space projection structure curve; the first curve and the second curve are stretched downward for a distance using the "stretch" command, and then the spiral line is generated using the "spiral" command, and the spiral line is generated using the "projection" command. The "Shadow Curve" command is used to project the spiral line onto two stretching sheets respectively. The two stretching sheets have a common Z axis. A straight line is drawn along the Z axis to connect the two stretching sheets, and the "Bridge Curve" command is used to complete the line drawing of a ligament structure. Finally, the "Tube" command is used to generate a ligament solid model with a certain diameter. After completing the design of one ligament structure, the "Rotation Array" is used to complete the structural design of the remaining ligaments. Then, the first disc-shaped body is kept stationary, and the second disc-shaped body is rotated 60° to 65° clockwise, or the second disc-shaped body is kept stationary, and the first disc-shaped body is rotated 60° to 65° counterclockwise to complete the design of the main structure model.

[0017] S3, 4D printing: export the model file of the 3D drawing software into a file type format that can be recognized by the 4D printer. Based on the three basic principles that the model cannot be placed in the air, the support structure should be minimized, and the model cannot exceed the boundary of the printer, import the model into the slicing software, place it flat in a suitable position, and add support structures to it respectively; set the slicing parameters and print; dissolve the support structure to obtain the main structure framework;

[0018] S4. Prepare a flow-blocking membrane, connect the main structure and the flow-blocking membrane with sutures; and coat urokinase or reteplase on the outside of the waist flow-blocking membrane.

[0019] Furthermore, in S1, the preparation process of the raw materials is as follows: the polylactic acid is placed in a vacuum drying oven at 55-65°C and dried for more than 24 hours, and then the dried polylactic acid and polyethylene glycol (relative molecular mass is 2000) are pre-mixed evenly, and the weight ratio of polylactic acid to polyethylene glycol is 9:1; then it is added to the barrel of the screw extruder to prepare for melt blending, the blending temperature is 1630-1670°C, and a wire with a diameter of 1.75 mm is prepared by gas-assisted melt extrusion.

[0020] Furthermore, in S2, the diameter of the ligament is 0.8 mm, and the diameters of the first disc-shaped body, the second disc-shaped body and the total height of the model are determined according to the actual size of the patient's heart defect.

[0021] Further, the flow-blocking film preparation process is as follows:

[0022] A. Use drawing software to draw a mask, and use the mask to form micro-nanoscale structures on silicon wafers through photolithography technology;

[0023] B. Place the silicon wafer on the receiving device of the electrospinning machine;

[0024] C. Place polylactic acid in an organic solvent until the polylactic acid is dissolved and stir evenly;

[0025] D. After injecting the polylactic acid solution into the syringe, connect the syringe to the spinneret;

[0026] E. Apply high voltage to the spinneret to eject a charged polymer jet;

[0027] F. The jet is received by the silicon wafer and constructed into a fiber membrane with nanostructure;

[0028] G. The cell growth factor is adhered to the surface of the nano-microstructure fiber membrane by the immersion method to prepare a flow-blocking membrane.

[0029] The beneficial effects of the present invention are:

[0030] The present invention uses 4D printing to form a main structure in one piece, and the bionic network structure of the main structure that simulates the wavy microstructure can show a nonlinear "J" type stress-strain curve similar to biological tissues such as skin and blood vessels;

[0031] The present invention has strong supporting force, clamps the primary septum and the secondary septum to form an effective occlusion. According to the actual situation of the patient (transthoracic cardiac ultrasound TTE), a personalized PFO occluder is formed by 4D printing. The PFO occluder has a high degree of size fit with the patient's site and has a good postoperative occlusion effect. The double discs rotate 60° to compensate for the mechanical properties of the material, which is more in line with the "J"-shaped stress-strain mechanical characteristics of biological tissues / organs. It conforms to the movement of the heart structure, ensures the stability of the clamped tissue morphology, conforms to the heart movement and the swing of the atrial septum, and does not wear the tissue or cause long-term tissue perforation. There are low points on the disc surface, which can automatically lock the edges, and the disc surface is stable, which is conducive to the deposition and coverage of cells in the blood, accelerates endothelialization, and reduces postoperative thrombosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. Among them:

[0033] Figure 1 FIG. 4 is a schematic diagram of the appearance of a PFO occluder according to an embodiment of the present invention.

[0034] Figure 2 Schematic diagram of the cross-sectional structure of a four-ligament PFO occluder according to an embodiment of the present invention.

[0035] Figure 3 It is a three-dimensional schematic diagram of the main structure of the four-ligament PFO occluder according to an embodiment of the present invention.

[0036] Figure 4 FIG. 1 is a schematic top view of the main structure of the four-ligament PFO occluder according to an embodiment of the present invention.

[0037] Figure 5 It is a front view schematic diagram of the main structure of the four-ligament PFO occluder according to an embodiment of the present invention.

[0038] Figure 6 This is a schematic diagram of the main structure of the six-ligament PFO occluder according to an embodiment of the present invention.

[0039] Figure 7 FIG. 4 is a three-dimensional schematic diagram of the main structure of the eight-ligament PFO occluder according to an embodiment of the present invention.

[0040] Figure 8 Schematic diagram of the structure of a single ligament according to an embodiment of the present invention.

[0041] Fig. 9 This is the main structure design process of the six-ligament PFO occluder according to the embodiment of the present invention; wherein:

[0042] Fig. 9 (a) is a schematic diagram of the first curve;

[0043] Fig. 9 (b) is a schematic diagram of the second curve;

[0044] Fig. 9 (c) is a schematic diagram of two stretched sheets;

[0045] Fig. 9 (d) is a schematic diagram of the connection of straight lines drawn along the Z axis;

[0046] Fig. 9 (e) is a schematic diagram of a ligament solid model;

[0047] Fig. 9 (f) is a schematic diagram of the six-ligament main structure model;

[0048] Fig. 9 (g) is a schematic diagram of the support structure;

[0049] Fig. 9 (h) is a schematic diagram of checking the generated model layer by layer.

[0050] Fig.10 The deformation process of the four-ligament PFO occluder according to an embodiment of the present invention; wherein:

[0051] Fig.10(a) shows the main structure of the four ligaments at room temperature;

[0052] Fig.10 (b) shows the main structure of the four ligaments after deformation;

[0053] Fig.10 (c) in the figure shows the main structure of the four ligaments after restoration.

[0054] Fig.11 The deformation process of the eight-ligament PFO occluder according to an embodiment of the present invention; wherein:

[0055] Fig.11 (a) shows the main structure of the eight ligaments at room temperature;

[0056] Fig.11 (b) shows the main structure of the four ligaments after deformation;

[0057] Fig.11 (c) shows the main structure of the four ligaments in recovery;

[0058] Fig.11 (d) is a top view of the main structure of the four ligaments after restoration;

[0059] Fig.11 (e) is a bottom view of the main structure of the four ligaments after restoration;

[0060] Fig.12 Schematic cross-sectional view of the ligament of the PFO occluder according to an embodiment of the present invention.

[0061] In the figure: 1-first disc-shaped body, 2-second disc-shaped body, 3-waist, 4-connector, 5-blocking membrane, 6-first straight line segment, 7-first spiral segment, 8-mid-waist straight line segment, 9-second spiral segment, 10-second straight line segment. DETAILED DESCRIPTION

[0062] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0063] In the description of the present invention, the terms "longitudinal", "lateral", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and do not require that the present invention must be constructed and operated in a specific orientation. Therefore, they should not be understood as limitations on the present invention. The terms "connected" and "connected" used in the present invention should be understood in a broad sense. For example, they can be fixed connections or detachable connections; they can be directly connected or indirectly connected through intermediate components. For ordinary technicians in this field, the specific meanings of the above terms can be understood according to specific circumstances.

[0064] The present invention will be described in detail below with reference to the accompanying drawings and in combination with embodiments. It should be noted that the embodiments and features in the embodiments of the present invention can be combined with each other without conflict.

[0065] like Figures 1 to 8 As shown, a PFO occluder based on 4D printing technology includes a main structure, a flow-blocking membrane 5 wrapped outside the main structure, and a suture; the main structure includes a first disc-shaped body 1, a second disc-shaped body 2, a waist 3 and a connector 4, the first disc-shaped body 1 and the second disc-shaped body 2 are connected through the waist 3, the connector 4 is connected to the center of the outer end surface of the second disc-shaped body 2, and the connector 4 is used to connect with the externally transported guide wire; the main structure and the flow-blocking membrane 5 are connected by sutures; the flow-blocking membrane 5 is a fiber membrane with a nano-microstructure of cell growth factors adhered to the surface;

[0066] The main structure is integrally formed by 4D printing; the main structure includes a plurality of special-shaped ligaments, and only the ends of each ligament intersect on the axis of the main structure; in the naturally unfolded state, the ligaments of the main structure are not in contact; all ligaments are arranged in a circular array around the axis of the main structure; Figure 8 As shown, the ligament includes a first straight segment 6, a first spiral segment 7, a mid-waist straight segment 8, a second spiral segment 9 and a second straight segment 10 connected in sequence; the first straight segments 6 and the first spiral segments 7 of all the ligaments constitute a first disc-shaped body 1, the mid-waist straight segments 8 of all the ligaments constitute the waist 3 of the main structure, and the second spiral segments 9 and the second straight segments 10 of all the ligaments constitute a second disc-shaped body 2.

[0067] Furthermore, the first spiral segment 7 and the second spiral segment 9 of the ligament do not overlap each other, the first spiral segment 7 / the second spiral segment 9 can be regarded as starting from the first straight segment 6 / the second straight segment 10 and extending to the mid-waist straight line, and the included angle of the projection of the first straight segment 6 and the second straight segment 10 of each ligament on the perpendicular plane between the two is 60° to 65° (for example, 60°, 60.5°, 61°, 62°, 63°, 64° or 65°); the unique ligament shape design of the present invention is more in line with the "J" type stress-strain mechanics characteristics of biological tissues / organs; the number of the ligaments can be 4 to 10, taking the number of ligaments as 4, 6 or 8 as an example, Figure 3 , Figure 4 , Figure 5 This is a schematic diagram of the main structure of the four-ligament PFO occluder; Figure 6 , Figure 7 Schematic diagrams of the main structures of six-ligament and eight-ligament PFO occluders. The diameter of the ligament is 0.7mm-0.8mm, the diameter of the first disc 1 is 15mm-17mm, and the diameter of the second disc 2 is 19mm-21mm. In terms of specific dimensions, referring to the dimensions of PFO occluders currently used in the market, the conventional dimensions are determined as follows: the diameters of the left and right discs are 20mm and 16mm respectively, the total height of the PFO occluder is 10mm, and the diameter of the ligament is 0.8mm.

[0068] Further, such as Figures 3 to 9 As shown, the inner ends of all the first straight line segments 6 have a common end, and the outer ends extend radially and evenly; the inner ends of all the second straight line segments 10 have a common end, and the outer ends extend radially and evenly to provide the disk surface of the first disk-shaped body 1 and the second disk-shaped body 2; the first spiral segment 7 and the second spiral segment 9 have the same rotation direction.

[0069] Furthermore, a coating is provided at the flow-blocking membrane 5 at the waist 3, and the coating component is urokinase or reteplase.

[0070] The present invention also proposes a method for preparing the aforementioned PFO occluder based on 4D printing technology, comprising the following steps:

[0071] S1. Preparation of raw materials: melt-blending polylactic acid (PLA) and polyethylene glycol (PEG), and preparing filaments with a diameter of 1.75 mm by melt extrusion;

[0072] S2. PFO occluder design: Based on the wave-shaped bionic design concept, the main structure is designed using 3D drawing software; the first reference surface corresponding to the first disc-shaped body 1 is constructed, such as Fig. 9As shown in (a) of FIG. 1 , the first curve is drawn using the "artistic spline" command as the spatial projection structure curve of the first straight line segment 6 and the first spiral segment 7. The shape of the "artistic spline" refers to the shape of the existing occluder. Similarly, a second reference plane corresponding to the two disc-shaped bodies is constructed, as shown in FIG. Fig. 9 As shown in (b) in FIG. 1 , a second curve is drawn using the “artistic spline” command as a spatial projection structure curve of the second straight line segment 10 and the second spiral segment 9; Fig. 9 As shown in (c) in the figure, the first curve and the second curve are stretched downward for a certain distance using the "Stretch" command, and then the "Spiral" command is used to generate a spiral line, and the "Project Curve" command is used to project the spiral line onto the two stretching sheets, respectively. The two stretching sheets have a common Z axis; Fig. 9 As shown in (d) in the figure, a straight line is drawn along the Z axis to connect the two stretching sheets, and the "bridge curve" command is used to draw a line of a ligament structure, as shown in Fig. 9 As shown in (e) in the figure, the "tube" command is used to generate a ligament solid model with a certain diameter; after completing the design of a ligament structure, as shown in Fig. 9 As shown in (f) in the figure, use the "rotate array" command to complete the structural design of the remaining ligaments, then keep the first disc 1 stationary and rotate the second disc 2 clockwise by 60° to 65°, or keep the second disc 2 stationary and rotate the first disc 1 counterclockwise by 60° to 65° (here clockwise is based on Figures 1 to 9 The first disc-shaped body 1 with a smaller size is on the top and the second disc-shaped body 2 with a larger size is on the bottom), so that the final included angle between the first straight line segment 6 and the second straight line segment 10 on their mid-vertical plane is about 60°, completing the design of the main structure model; the double discs of the PFO occluder of the present invention rotate 60° to compensate for the mechanical properties of the material, which is more in line with the "J-shaped" stress-strain mechanical characteristics of biological tissues / organs,

[0073] S3, 4D printing: export the model file of the 3D drawing software to a file type format recognizable by the 4D printer, such as STL format; based on the three basic principles that the model cannot be placed in the air, the support structure is minimized, and the model cannot exceed the boundary of the printer, import the model into the slicing software, place it flat in a suitable position, and add support structures to it respectively; because the material to be printed is modified polylactic acid (PLA), before starting slicing, select only Raft in the base plate addition, and select all support structures, so that the software can use the algorithm to add support to the model, such as Fig. 9(g) in the figure shows the model after adding supports. The bottom surface of the model used for 4D printing is preferably flat, which can increase the stability of the model without adding supports. For example, the base can be directly cut with a plane to obtain a flat bottom surface, and the warping deformation of the model can be reduced. After the model is imported into the slicing software, it is placed flat in a suitable position and supports are added to it respectively. The overall model preview after slicing is shown in the figure below. Fig. 9 As shown in (g) in the figure; after slicing, check whether the model base is complete, whether the support is added, and whether the model is damaged or missing. The steps for checking layer by layer are as follows Fig. 9 As shown in (h); 4D printing the main frame, and finally dissolving the support structure to obtain the main structure frame; preferably, the ligaments of the 4D printed main structure frame are provided with convex and concave strip microstructures, Fig.12 The middle is a schematic diagram of the cross-sectional shape of the ligament. The convex and concave microstructure can increase the anchoring force of the occluder, thereby improving the performance stability of the occluder.

[0074] S4, preparing the flow-blocking membrane 5, connecting the main structure and the flow-blocking membrane 5 with sutures; coating the outside of the flow-blocking membrane 5 at the waist 3 with urokinase or reteplase.

[0075] The suture is made of biodegradable polymer material with a diameter of 0.1 mm to 0.5 mm, and can be, for example, a surgical absorbable and degradable suture. When in use, the flow-blocking membrane 5 is first cut to the size of the main structure and then sutured.

[0076] Further, in S1, the preparation process of the raw materials is as follows: polylactic acid is placed in a vacuum drying oven at 60°C and dried for 24 hours, and then the dried polylactic acid and polyethylene glycol (relative molecular weight is 2000) are pre-mixed evenly, and the weight ratio of polylactic acid to polyethylene glycol is 9:1; then it is added to the barrel of a screw extruder to prepare for melt blending, and the blending temperature is 1650°C, and a wire with a diameter of 1.75 mm is prepared by gas-assisted melt extrusion; in the process of wire preparation, gas-assisted extrusion is used to reduce extrusion friction, thereby reducing the tensile deformation during wire extrusion, thereby improving the molding quality and precision of the wire; in the present invention, polylactic acid (PLA) is modified, and the glass transition temperature (T g ) is about 50-60℃, near which it will absorb heat and undergo phase change; Fig.10 , 11 As shown in the figure, the four-ligament and eight-ligament main structures are taken as examples to explore their shape memory recovery effects; Fig.10 , 11 The morphology of the main structures of the middle four ligaments and eight ligaments under normal conditions and after recovery shows that they can be transported through the delivery tube after deformation, and there is no obvious difference between the shapes recovered after compression and the normal shapes.

[0077] The present invention can show a nonlinear "J-shaped" stress-strain curve similar to biological tissues such as skin and blood vessels by simulating a bionic network structure of a wavy microstructure; this structure can accurately simulate the mechanical properties of biological tissues, and its characteristics are that it exhibits a low modulus at low strain, and the modulus gradually increases with the increase of strain, and the modulus increases sharply at high strain. The main structure can conform to the deformation of biological tissues at low strain, thereby reducing tissue wear or perforation caused by the mismatch of mechanical properties between the stent and the biological tissue. At the same time, under high strain conditions, the high elastic modulus of the structure provides a "strain limitation" effect, preventing excessive deformation of biological tissues and the main structure. The present invention adopts 4D printing technology to form an integrated occluder frame, which has strong supporting force, clamps the primary septum and the secondary septum to form an effective occlusion. According to the actual situation of the patient (transthoracic cardiac ultrasound TTE), 4D printing is used to form a personalized PFO occluder. The PFO occluder has a high degree of fit with the size of the patient's site, and the postoperative occlusion effect is good; the cross-section of the ligament of the occluder frame formed by 4D printing is a convex and concave microstructure, which can increase the anchoring force of the occluder, thereby improving the performance stability of the occluder. The double disc rotates 60° to compensate for the mechanical properties of the material, which is more in line with the "J-shaped" stress-strain mechanical characteristics of biological tissues / organs. While conforming to the movement of the heart structure, it ensures the stability of the clamped tissue morphology, conforms to the heart movement and the swing of the atrial septum, and does not wear the tissue or long-term tissue perforation problems; there are low points on the disc surface, which can automatically lock the edge, and the disc surface is stable, which is conducive to the deposition and coverage of cells in the blood, accelerates endothelialization, and reduces postoperative thrombosis.

[0078] Furthermore, the preparation process of the flow-blocking film 5 is as follows:

[0079] A. Use drawing software to draw a mask, and use the mask to form micro-nanoscale structures on silicon wafers through photolithography technology;

[0080] B. Place the silicon wafer on the receiving device of the electrospinning machine;

[0081] C. Place polylactic acid in an organic solvent until the polylactic acid is dissolved and stir evenly;

[0082] D. After injecting the polylactic acid solution into the syringe, connect the syringe to the spinneret;

[0083] E. Apply high voltage to the spinneret to eject a charged polymer jet;

[0084] F. The jet is received by the silicon wafer and constructed into a fiber membrane with nanostructure;

[0085] G. The cell growth factor is adhered to the surface of the nanostructured fiber membrane by an immersion method to prepare a flow-blocking membrane 5.

[0086] The present invention adheres cell growth factors to the surface of the first disc-shaped body 1 baffle 5 and the second disc-shaped body 2 baffle 5 by constructing a micro-nanoscale topological structure, thereby enhancing the biological activity of the cardiac occluder and regulating its degree of biological functionalization to guide the healing, repair and remodeling of the surrounding tissues of the defect and restore its normal physiological function; at the same time, its biocompatibility is enhanced, thereby reducing postoperative complications. Compared with the main structure, their main materials are consistent, both are polylactic acid, so the overall degradation rate of the occluder is consistent and controllable, which is beneficial to the patient's postoperative recovery.

[0087] Furthermore, urokinase or reteplase is dissolved and applied only to the waist 3 baffle film 5 to obtain the waist 3 baffle film 5 with an anticoagulant coating. The anticoagulant coating of the waist 3 baffle film 5 can dissolve possible mural thrombi and reduce the risk of new cerebral infarction caused by the detachment of mural thrombi due to implantation.

[0088] Next, we will use UG NX 12.0 to explain the specific design process:

[0089] Based on the wave-shaped bionic design concept and industry standards, the PFO occluder model was designed using UG NX 12.0 software. Taking the 6-ligament cardiac occluder as an example, the design steps are as follows: Fig. 9 There are 6 ligaments. The design idea is to use the array command to form after completing one ligament. First, design the structure of one ligament, and use the art spline command to draw the spatial projection structure curve of the upper disk ligament on the plane 9.5mm away from the bottom surface, as shown in the figure. Fig. 9 (a); Similarly, set a reference plane and use the art spline command to draw the spatial projection structure curve of the lower disk ligament, as shown in Fig. 9 (b) As shown; the curves drawn in the first two steps are stretched downward for a certain distance using the stretch command, and then the spiral line is generated using the spiral command, and the spiral line is projected onto the stretched sheet using the project curve command, as shown in Fig. 9 (c) Draw a straight line at the intersection of the two along the Z axis, and use the bridge curve command to draw a line of a ligament structure, as shown in Fig. 9 (d) As shown; Use the pipe command to set the inner diameter to 0 and the outer diameter to 0.8 mm, as shown in Fig. 9 (e) Finally, use the array feature command and set the number of circular arrays to 6, as shown in Fig. 9 As shown in (f), after the array, the first disc-shaped body 1 and the second disc-shaped body 2 are relatively rotated 60° clockwise to complete the model design of the PFO occluder. Among them, the diameter of the ligament is 0.8 mm, and the diameters of the first disc-shaped body 1 and the second disc-shaped body 2 and the total height of the model are determined according to the actual size of the patient's heart defect.

[0090] In addition, the present invention also uses Solidworks software to perform numerical simulation on the model of the multi-ligament structure. The results show that the waist of the four-ligament PFO occluder is subjected to the greatest stress, which is about 1.5×10 6 N / m 2 , and the yield strength is 5×10 7 N / m 2 , indicating that the material did not yield under this stress level. Under a force of 1N, the waist of the six-ligament and eight-ligament occluders was subjected to the greatest stress, which was approximately 1.0×10 6 N / m 2 , 8.8×10 5 N / m 2 , and the yield strength of the material is 5×10 7 N / m 2 , indicating that no yielding occurs at this stress level.

[0091] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention are within the scope of protection of the pending claims of the present invention.

Claims

1. A PFO occluder based on 4D printing technology, comprising a main structure and a flow-blocking membrane (5) wrapped outside the main structure, characterized in that: The main structure comprises a first disc-shaped body (1), a second disc-shaped body (2), a waist (3) and a connector (4); the first disc-shaped body (1) and the second disc-shaped body (2) are connected via the waist (3); the connector (4) is connected to the center of the outer end surface of the second disc-shaped body (2); the connector (4) is used to connect to a guide wire for external delivery; The main structure is integrally formed by 4D printing; the main structure comprises a plurality of special-shaped ligaments, the ends of each ligament intersect on the axis of the main structure, and all the ligaments are arranged in a circular array around the axis of the main structure; the ligament comprises a first straight segment (6), a first spiral segment (7), a mid-waist straight segment (8), a second spiral segment (9) and a second straight segment (10) connected in sequence; the first straight segments (6) and the first spiral segments (7) of all the ligaments constitute a first disc-shaped body (1), the mid-waist straight segments (8) of all the ligaments constitute a waist (3) of the main structure, and the second spiral segments (9) and the second straight segments (10) of all the ligaments constitute a second disc-shaped body (2).

2. The PFO occluder based on 4D printing technology according to claim 1, characterized in that: The included angle between the projections of the first straight line segment (6) and the second straight line segment (10) of each ligament on the perpendicular plane between the two is 60° to 65°, and the number of the ligaments is 4 to 10.

3. The PFO occluder based on 4D printing technology according to claim 1, characterized in that: The inner ends of all the first straight line segments (6) are at the same end, and the outer ends are radially and evenly extended; the inner ends of all the second straight line segments (10) are at the same end, and the outer ends are radially and evenly extended; the first spiral segment (7) and the second spiral segment (9) have the same direction of rotation.

4. The PFO occluder based on 4D printing technology according to claim 1, characterized in that: It also comprises a suture line, through which the main structure and the flow-blocking membrane (5) are connected; the flow-blocking membrane (5) is a fiber membrane with a nano-microstructure having cell growth factors adhered to its surface.

5. The PFO occluder based on 4D printing technology according to claim 1, characterized in that: The flow-blocking membrane (5) at the waist (3) is provided with a coating, and the coating component is urokinase or reteplase.

6. The PFO occluder based on 4D printing technology according to claim 1, characterized in that: The diameter of the ligament is 0.7 mm to 0.8 mm, the diameter of the first disc-shaped body (1) is 15 mm to 17 mm, and the diameter of the second disc-shaped body (2) is 19 mm to 21 mm.

7. A method for preparing a PFO occluder based on 4D printing technology as claimed in any one of claims 1 to 5, characterized in that: The following steps are involved: S1. Preparation of raw materials: melt-blending polylactic acid and polyethylene glycol, and preparing filaments by melt extrusion; S2. Design of PFO occluder: Based on the wave-shaped bionic design concept, the main structure is designed using 3D drawing software; a first reference plane corresponding to the first disc-shaped body (1) is constructed, and the first curve is drawn using the "artistic spline" command as the spatial projection structure curve of the first straight line segment (6) and the first spiral segment (7); similarly, a second reference plane corresponding to the second disc-shaped body is constructed, and the second curve is drawn using the "artistic spline" command as the spatial projection structure curve of the second straight line segment (10) and the second spiral segment (9); the first curve and the second curve are stretched downward for a certain distance using the "stretch" command, and then the spiral line is generated using the "spiral" command, and the spiral line is generated using the "stretch" command. The "Project Curve" command projects the spiral line onto two stretching sheets respectively, and the two stretching sheets have a common Z axis; a straight line is drawn along the Z axis to connect the two stretching sheets, and the "Bridge Curve" command is used to complete the line drawing of a ligament structure, and finally the "Tube" command is used to generate a ligament solid model with a certain diameter; after completing the design of a ligament structure, the "Rotation Array" is used to complete the structural design of the remaining ligaments, and then the first disc-shaped body (1) is fixed, and the second disc-shaped body (2) is rotated clockwise by 60° to 65°, or the second disc-shaped body (2) is fixed, and the first disc-shaped body (1) is rotated counterclockwise by 60° to 65°, to complete the design of the main structure model; S3, 4D printing: export the model file of the 3D drawing software into a file type format that can be recognized by the 4D printer. Based on the three basic principles that the model cannot be placed in the air, the support structure should be minimized, and the model cannot exceed the boundary of the printer, import the model into the slicing software, place it flat in a suitable position, and add support structures to it respectively; set the slicing parameters and print; Dissolving the supporting structure to obtain the main structural framework; S4, preparing a flow-blocking membrane (5), connecting the main structure and the flow-blocking membrane (5) with sutures; and coating the outside of the flow-blocking membrane (5) at the waist (3) with urokinase or reteplase.

8. The method for preparing a PFO occluder based on 4D printing technology according to claim 7, characterized in that: In S1, the preparation process of the raw materials is as follows: polylactic acid is placed in a vacuum drying oven at 55-65°C and dried for more than 24 hours, and then the dried polylactic acid and polyethylene glycol (relative molecular mass is 2000) are pre-mixed evenly, and the weight ratio of polylactic acid to polyethylene glycol is 9:1; then it is added to the barrel of the screw extruder to prepare for melt blending, the blending temperature is 1630-1670°C, and a wire with a diameter of 1.75 mm is prepared by gas-assisted melt extrusion.

9. The method for preparing a PFO occluder based on 4D printing technology according to claim 7, characterized in that: In S2, the diameter of the ligament is 0.8 mm, and the diameters of the first disc-shaped body (1) and the second disc-shaped body (2) and the total height of the model are determined according to the actual size of the patient's heart defect.

10. The method for preparing a PFO occluder based on 4D printing technology according to claim 7, characterized in that: The preparation process of the flow-blocking film (5) is as follows: A. Use drawing software to draw a mask, and use the mask to form micro-nanoscale structures on silicon wafers through photolithography technology; B. Place the silicon wafer on the receiving device of the electrospinning machine; C. Place polylactic acid in an organic solvent until the polylactic acid is dissolved and stir evenly; D. After injecting the polylactic acid solution into the syringe, connect the syringe to the spinneret; E. Apply high voltage to the spinneret to eject a charged polymer jet; F. The jet is received by the silicon wafer and constructed into a fiber membrane with nanostructure; G. Cell growth factors are adhered to the surface of the nanostructured fiber membrane by an immersion method to prepare a flow-blocking membrane (5).

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