Degradable aortic dissection repair patch and preparation method thereof

Abstract

The invention relates to the field of medical biological materials, and discloses a degradable aortic dissection repair patch and a preparation method thereof.The preparation method comprises the following steps that a fiber sheet of a double-face structure is prepared in an electrostatic spinning mode, and a polycaprolactone solution is pumped from an injector; carrying out natural air drying treatment on the electrostatic spinning sheet, and cutting the electrostatic spinning sheet into a circular patch unit through a die cutting process; the cut patch is placed on the surface of a prefabricated nickel-titanium alloy conveyor with the orientation face facing downwards; an adhesive is used on the surface of the disordered fiber surface of the patch in a uniform or point coating manner; carrying out sterilization treatment on the patch conveying system; and appearance integrity inspection and patch and support connection strength detection are carried out on the manufactured patch system. The electrostatic spinning technology is controlled to be in a standing rotating deposition mode in a staged mode, a seamless integrated structure of an inner side disordered multidirectional pore layer and an outer side annular directional stress layer is formed on the same fiber sheet, shearing can be effectively buffered through a multidirectional pore network, and the effect that stress distribution is more uniform is achieved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical biomaterials, in particular to a degradable aortic dissection repair patch and a preparation method thereof. BACKGROUND

[0002] The arterial wall is composed of three layers of intima, media and adventitia. Aortic dissection is a condition in which the middle layer of the aorta separates to form a true and false double lumen. In current surgical procedures, there is still a problem that the diseased artery cannot be completely removed at the aortic root, and the remaining aortic dissection is prone to further development and cause a series of subsequent complications. Currently, commercial biological protein glue is used to adhere the intima and adventitia of the aortic dissection tear, but the biological glue after solidification has high brittleness, and its mechanical properties cannot adapt to the flexibility of natural blood vessel tissue. When sutured with artificial blood vessel material, the biological glue is easily broken, and the micro-holes formed at the suture site can cause blood permeation, and the degradation products also have cytotoxicity, which can easily cause subsequent complications and endanger the safety of patients; In addition, stent grafts still have limitations in endovascular intervention therapy and cannot completely fit the patient's aorta, which has the risk of insufficient or excessive expansion, which can further damage the blood vessels. The materials used in surgical procedures and endovascular grafts, such as polyester or Teflon, have high rigidity, which leads to mechanical mismatch between the device and the natural tissue, thereby increasing the heart load and downstream pressure wave conduction. These grafts are inert and non-degradable, and do not actively promote the coagulation and absorption of the false lumen, nor do they promote vascular remodeling and regeneration, thereby preventing the complete recovery of the blood vessel wall to its function. Therefore, developing a new type of adhesive biodegradable patch with high safety, which can adapt to the mechanical properties of natural blood vessel tissue and enable, is one of the key directions of research on medical devices for treating aortic dissection. SUMMARY

[0003] In view of the deficiencies of the prior art, the present application provides a degradable aortic dissection repair patch and a preparation method thereof, which solves the problem that the prior art uses a single static or continuous rotation electrospinning process, resulting in a single fiber arrangement structure, which cannot take into account the circumferential mechanical reinforcement and is difficult to meet the multi-directional porosity biological permeation, and the patch is prone to tear failure in a high blood pressure environment.

[0004] To achieve the above object, the present application is realized by the following technical scheme: a preparation method of a degradable aortic dissection repair patch, comprising the following steps: A fiber sheet with a double-sided structure is prepared by electrospinning, and a polycaprolactone solution is pumped from a syringe and deposited on a drum-type collector to form a fiber membrane under the action of an electric field; The electrospun sheet is naturally air-dried and cut into a circular patch unit by a die-cutting process; The cut patch is placed on the surface of the prepared nickel-titanium alloy conveyor with the oriented surface facing down, and the patch is sewn onto the conveyor using water-soluble sutures to form a patch delivery system; An adhesive including a cyanoacrylate component is applied to the surface of the disordered fiber of the patch in a uniform or spot coating manner, and the coating pattern includes an edge annular region and a central cross-shaped region; The patch delivery system is sterilized, and the system is packaged within a specified time after the adhesive is activated; The appearance integrity of the prepared patch system is checked, and the connection strength of the patch and the stent is detected. After passing the inspection, the system is stored in a sterile and low-temperature environment for standby use.

[0005] Preferably, when the deposition forms a fiber membrane, the deposition time of the polycaprolactone solution is divided into 2 hours, wherein in the first hour, the collector remains stationary to form an unordered fiber layer, and in the second hour, the collector rotates clockwise at 1000 r / min to form an ordered fiber layer. After 2 hours of polycaprolactone solution deposition, a double-sided electrospun sheet is obtained.

[0006] Preferably, the solution is pumped using a syringe, which is placed on an injection pump system and used to advance at a solvent flow rate of 2000 uL / h, and the injection pump is placed horizontally at a distance of 18.0 cm from the collector.

[0007] Preferably, a voltage of 16.0-20.0 kV is applied between the injection pump and the collector during solvent flow advancement, and the collector is a cylindrical barrel made of metal material.

[0008] Preferably, the natural air drying treatment of the electrospun sheet includes the following steps: The double-sided electrospun sheet after completing the spinning deposition is peeled off from the surface of the collector and placed on the surface of a non-woven fabric or an inert flat plate; In a clean bench, the electrospun sheet is flattened and naturally spread on the flat surface; Then the unfolded electrospun sheet is placed and cooled for 1 hour in a dust-free space; After air drying, the electrospun sheet is taken out for preliminary visual inspection to confirm that the surface is free of obvious liquid, no adhesion or wrinkles, and then transferred to the subsequent step.

[0009] Preferably, the cutting process is used to cut the electrospun sheet into a circular patch unit, which includes the following steps: The air-dried electrospun sheet is laid flat on the die-cutting platform, and the electrospun sheet is placed in the positioning fixture to maintain the spinning direction; The cutting is completed by manually pressing or mechanically controlling the die-cutting head to press down, and the cutting uses a circular die with a diameter of 10 mm; After cutting, the circular patch unit is taken out from the mold using sterile tweezers, and the qualified patch unit is temporarily placed on the surface of the prepared nickel-titanium alloy conveyor, so as to complete the cutting.

[0010] Preferably, the electrospun round patch substrate in the patch delivery system is uniformly distributed with a micro pipette to form a circle along the outer edge of the electrospun round patch and a cross in the center of the patch, so as to prepare an adhesive patch delivery system. The adhesive, which includes a cyanoacrylate-based adhesive, is configured 1-5 days in advance before use, and the adhesive is stored in a space at 4 DEG C.

[0011] Preferably, the step of point coating the adhesive on the unordered fiber surface of the patch is carried out by using a micro pipette to drop the cyanoacrylate solution on the edge annular area and the central cross area of the patch in sequence, and the total volume of the point coating is controlled to be less than 50 mu L, and the adhesive solution is allowed to stand for 10 minutes after the point coating to complete the pre-permeation.

[0012] Preferably, the step of suturing the patch to the conveyor includes: The ordered fiber surface of the patch is placed downward on the outer surface of the nickel-titanium alloy conveyor, and is sutured to the head, tail, left side and right side of the electrospun round patch by water-soluble sutures, and the suturing mode is manual puncture fixation.

[0013] A degradable aortic dissection repair patch, comprising: A double-sided structure fiber sheet, the fiber sheet has an ordered fiber structure on one side and an unordered fiber structure on the other side; The double-sided structure fiber sheet includes unordered fibers obtained by standing still, and ordered fibers obtained by deposition of a collector rotating clockwise; The fiber sheet is processed into a circular patch, and the ordered surface of the patch is connected to the conveyor, and the connection is positioned by at least four sutures; The unordered surface of the patch has a patterned structure formed by a cyanoacrylate adhesive, and the pattern includes an annular area around the edge of the patch and a cross area through the center of the patch.

[0014] The present application provides a degradable aortic dissection repair patch and a preparation method thereof. 1、The present application controls the electrospinning process in stages to form a seamless integrated structure of an unordered multidirectional pore layer on the inside and a ring-shaped directional stress layer on the outside on the same fiber sheet, so as to achieve the effects of bearing ring-shaped tension in a high blood pressure pulsation environment, improving mechanical stability, effectively buffering shear through the multidirectional pore network, and more uniform stress distribution.

[0015] 2、The present application combines solvent static standing spontaneous webbing and collector rotation deposition, and the unordered layer has the functions of multidirectional guiding invasion and directional layer precise bearing of blood flow pulsatile pressure to cells and microvessels, so that the composite biomechanical and biological synergistic effect of accelerating endothelialization reconstruction and reducing early patch displacement and tearing risk is achieved.

[0016] 3、The present application adopts annular and cross-shaped patterned cyanoacrylate adhesive point coating on the unordered fiber surface, and only locally and efficiently seals and fixes the patch edge and central area, so that the effects of low-dose, controllable stress fracture, minimal postoperative adhesive residue and excellent early sealing performance are achieved. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 The present application is a method flow chart for preparing a degradable aortic dissection repair patch. DETAILED DESCRIPTION

[0018] The technical solutions of the present application will be described clearly and completely below in combination with the drawings of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0019] Please refer to the drawings of the present application Figure 1 The present application provides a degradable aortic dissection repair patch preparation method, which comprises the following steps: A fiber sheet with a double-sided structure is prepared by an electrospinning method, a polycaprolactone solution is pumped from a syringe, and a fiber membrane is formed on a drum-type collector by the action of an electric field; The electrospun sheet is naturally air-dried, and is cut into a circular patch unit by a die-cutting process; The cut patch is placed on the surface of a pre-prepared nickel-titanium alloy conveyor with the directional surface facing down, and the patch is sewn onto the conveyor by using a water-soluble suture by hand to form a patch conveying system; An adhesive is used on the unordered fiber surface of the patch in a uniform or point coating manner, the adhesive comprises a cyanoacrylate component, and the coating pattern comprises an annular edge area and a central cross-shaped area; The patch conveying system is sterilized, and the system is packaged within a specified time after the adhesive is activated; The appearance integrity of the prepared patch system is checked, and the connection strength of the patch and the stent is detected, and the system is stored in a sterile and low-temperature environment for standby use after passing the inspection.

[0020] When the fiber membrane is formed by deposition, the deposition time of the polycaprolactone solution is divided into two hours, wherein in the first hour, the collector remains stationary to form an unordered fiber layer, and in the second hour, the collector rotates clockwise at 1000 r / min to form an ordered fiber layer. After the polycaprolactone solution is deposited for 2 hours, a double-sided electrospun sheet is obtained.

[0021] Specifically, first, in the first hour of deposition, the collector remains stationary, and the polycaprolactone solution swings freely under the action of a high-voltage electric field to form a fiber network that is interwoven and has no obvious orientation. The unordered layer has a micro-porous structure that not only provides good permeability and drug carrier function, but also can closely adhere to the wet tissue surface when subsequently attached to the blood vessel wall, thereby playing a preliminary blocking and supporting role. The three-dimensional network pore structure formed by random deposition can effectively absorb external arterial wall micro-leakage, reduce blood side leakage, and reduce the risk of secondary bleeding. Subsequently, after the first hour, the collector rotates clockwise at a constant speed of 1000 r / min to continue deposition for the second hour. The centrifugal force and tangential velocity field caused by high-speed rotation cause the jet flow to stretch and orient when approaching the collection surface, and arrange into a highly consistent unidirectional fiber layer. The directional layer has significant mechanical anisotropy: the tensile strength and tear resistance in the fiber orientation direction are significantly enhanced, and can withstand the radial and circumferential mechanical loads generated by the arterial wall during pulsation; and the vertical direction remains flexible, which helps the patch to conform to the changes in the blood vessel curvature. The static and dynamic deposition modes are ingeniously combined, and a double-sided structure is obtained in a single process without subsequent splicing or layering technology, which not only simplifies the production process, but also avoids the risk of delamination between multiple layers. The synergistic effect of the macro-micro structure of the fiber provides better mechanical support and biocompatibility for the degradable aortic dissection repair patch.

[0022] The solution is pumped using a syringe placed on an injection pump system at a solvent flow rate of 2000 uL / h, and the injection pump is placed horizontally at a distance of 18.0 cm from the collector.

[0023] Specifically, the spinning solution is pushed by a syringe loaded on an injection pump system at a constant rate to ensure that the droplet stably transitions from the needle tip to the Taylor cone and forms a continuous jet flow. At this speed, the solution supply at the jetting port is neither too fast to cause unstable jetting nor too slow to cause needle blockage, so that the fiber diameter distribution is more uniform and the pore structure is more controllable. Constant flow rate can keep the stretching-solidification process under the action of the electric field in a dynamic balance, thereby directly affecting the radial shrinkage ratio of the fiber and the final mechanical properties. The spatial arrangement not only ensures sufficient evaporation channels for the solvent, but also avoids the dispersion of the filament flow caused by too long a distance or the splashing of the solution caused by too short a distance. The horizontally placed injection pump can also eliminate the gravity error caused by the height difference, so that the starting conditions of each spinning experiment are highly consistent, thereby improving the repeatability between batches.

[0024] A voltage of 16.0-20.0 kV is applied between the injection pump and the collector when the solvent flow is promoted, and the collector is a barrel made of a metal material.

[0025] Specifically, the polycaprolactone solution is driven to be stably sprayed from the needle tip to the collection surface. Within this voltage range, the electric field strength is sufficient to overcome the surface tension of the solution to form a fine and continuous Taylor cone filament flow structure, and it will not be too high to cause corona discharge or unstable spraying. By precisely controlling the voltage, the present application ensures that the draw ratio of the fiber is optimized synchronously with the solidification rate; The selected metal barrel collector not only has excellent electrical conductivity, can quickly neutralize the charge of the falling fiber, reduce the electrostatic repulsion between the fibers, thereby preventing the flying or scattering of the filaments during film formation, but also its cylindrical shape cooperates with the rotation mode to generate a stable tangential velocity field during the deposition of the oriented layer, helping the filament flow to spread and align uniformly on the rotating surface. By adjusting the voltage in combination with the rotating or stationary state of the metal barrel, the stretching-coagulation kinetics of the filament flow can be precisely controlled, and the orientation and laying pattern of the fibers can be adjusted by the morphology of the collection surface.

[0026] The electrospun sheet is naturally air-dried, including the following steps: The double-sided electrospun sheet after completing the spinning deposition is peeled off from the surface of the collector and placed on the surface of a non-woven fabric or an inert flat plate; In a clean bench, the electrospun sheet is flattened and naturally spread on the flat surface; Then the electrospun sheet after spreading is placed and cooled for 1 hour in a dust-free space; After the air-drying is completed, the electrospun sheet is taken out for preliminary examination by the naked eye, and it is confirmed that there is no obvious liquid attachment, no adhesion or wrinkle on the surface, and then it is transferred to the subsequent step.

[0027] Specifically, first, the double-sided electrospun sheet just peeled off from the metal collector is placed lightly on the surface of a non-woven fabric or an inert flat plate. At this time, the fiber still has some solvent residue, and if it is directly exposed to a forced drying environment, it is easy to cause sudden shrinkage of the fiber mesh and accumulation of internal stress. Using a non-woven fabric to support allows the filaments to slowly release solvent in the early stage, while avoiding local indentations or adhesion caused by direct contact with a rigid surface; Then, the spinning sheet is gently flattened in the clean bench, and is allowed to spread naturally on the flat surface without locking the edges of the spinning sheet, but allowing it to be slightly adjusted under the joint action of surface tension and gravity, so as to balance the internal stress distribution, and through the relaxation treatment, the three-dimensional pore structure of the fiber network is kept coherent, avoiding the occurrence of micro-cracks or wrinkles caused by constraint, so that the permeability and mechanical flexibility of the final membrane are kept in the best state, and then, the flattened spinning sheet is placed in a dust-free space for cooling for 1 hour. Natural cooling at room temperature not only helps the complete evaporation of the solvent, but also allows the polymer chain segments to have sufficient time for chain segment rearrangement and partial crystallization before losing fluidity. Finally, a preliminary visual inspection is performed to confirm that the surface of the spinning sheet is free of obvious liquid attachment, adhesion or wrinkles, and then it is transferred to the subsequent fixing or bonding process, so that micro-defects are removed in one drying and one inspection, greatly reducing the risk of loose bonding or local failure caused by film surface defects.

[0028] The die-cutting process is cut into a circular patch unit, including the following steps: The dried electrospun sheet is laid flat on the die-cutting platform, and the spinning sheet is placed in the positioning clamp to maintain the spinning direction; The cutting is completed by manually pressing or mechanically controlling the die-cutting head to press down, and the cutting uses a circular die with a diameter of 10 mm; After cutting, the sterile tweezers are used to take out the circular patch unit from the die, and the qualified patch unit is temporarily placed on the surface of the pre-prepared nickel-titanium alloy conveyor, thereby completing the cutting.

[0029] Specifically, first, the spinning sheet that has been naturally air-dried and has completed preliminary quality inspection is laid flat on the die-cutting platform and placed in a special positioning clamp to maintain the consistency of the fiber direction and the film tension. The entire double-sided electrospun film is converted into a high-uniformity circular patch unit with a diameter of 10 mm. During the cutting process, two modes of manual pressing and mechanical control of the die-cutting head are combined, and the mode is flexibly switched according to the production batch. When the die-cutting head is vertically pressed between the fiber layer and the bearing plate, the cutting die head is equipped with a fine tooth structure at the cutting edge. When pressed down, the fiber layer is quickly broken along the predetermined circumference without causing pulling or tearing damage; After cutting, the operator uses sterile tweezers to gently extract the circular patch unit and temporarily place it on the surface of the pre-designed nickel-titanium alloy conveyor. The microscopic fiber end face on the cutting surface still maintains a certain opening state, which is beneficial to the subsequent water-soluble suture puncture fixation and the preliminary penetration of the adhesive. Compared with direct manual cutting or laser cutting, the pressing process takes into account the efficiency and the low thermal damage requirement of biological materials. The processing is completed at normal temperature and pressure, avoiding the generation of heat-affected zones and reducing the risk of sudden breakage or scorching pollution.

[0030] The step of suturing the patch to the conveyor includes: The oriented fiber surface of the patch is placed facing down on the outer surface of the nickel-titanium alloy conveyor, and water-soluble sutures are respectively sutured at the head, tail, left side and right side of the electrospun round patch, and the suture method is manual puncture fixation.

[0031] Specifically, the oriented fiber patch prepared by electrospinning is combined with the nickel-titanium alloy conveyor, aiming to balance the initial mechanical fixation and subsequent biological integration performance. In this process, the oriented fiber surface of the patch is placed facing down on the outer surface of the conveyor, which not only ensures more direct contact between the fiber layer and the metal surface, but also takes advantage of the arrangement of the oriented fibers, so that the fiber and metal interface is more likely to form a micro-mechanical engagement under subsequent shear or bending load. In actual operation, water-soluble sutures are used to fix the patch, and manual puncture is used to pass through the edge of the fiber patch and adhere to the metal surface to provide sufficient fixation strength in the initial stage to resist external interference during operation or transportation, but it will not remain as a foreign body for a long time, avoiding continuous interference with cell growth or tissue healing. First, rely on sutures to ensure stable adhesion, and once the patch begins to integrate with the surrounding environment or the metal surface is subjected to subsequent processing, the sutures can gradually degrade over time, allowing the interface to shift to a more natural biological integration mode. For the selection of suture position, a fixed point is arranged at the head, tail, left side and right side of the patch. After puncture fixation at each edge, the tension is immediately evaluated to ensure that the patch is flat and tightly attached without excessive pulling. The key point of the mechanism here is that four-point or multi-point distribution of the fixed point can evenly disperse the edge stress, avoiding concentrated load that can cause fiber tearing or local edge lifting. In addition, by adjusting the tension immediately, the original micro arrangement of the fiber structure can be considered during fixation, reducing fiber deformation caused by excessive tightness or unevenness, thereby preserving the original function of the patch such as guiding cell directional growth or mechanical response. After suture, mechanical stability check should be performed immediately, such as mild vibration simulation or tensile test, and the suture or tightness adjustment should be made according to the situation.

[0032] Pointing the disordered fiber surface of the patch with adhesive is done by using a micropipette to drop cyanoacrylate solution on the edge annular area and central cross area of the patch, with a total volume controlled within 50 μL. The adhesive solution is allowed to stand for 10 minutes after being dropped to complete pre-permeation.

[0033] Specifically, first, the patch is fixed in place with the disordered fibers facing up, then a micro pipette is used to precisely drop the cyanoacrylate solution on the annular area at the edge of the patch and the cross-shaped area in the center. By partitioning, the adhesive is locally positioned in key positions without flooding the entire piece, forming multiple mechanical anchoring points while preserving the permeability and microstructure of the remaining fiber network. This distribution ensures both fixing strength and avoids fiber pore blockage or excessive hardening caused by large-area bonding, thus meeting the needs of subsequent cell or medium passage; After spot coating, the solution is left to stand for about 10 minutes to complete the pre-permeation process, based on the consideration of the permeation and initial polymerization rate of cyanoacrylate in the micro-fiber network. During this period, the micro-adhesive can penetrate into the disordered fiber gap through capillary action and form a preliminary micro-bond with the fiber surface, rather than just staying on the surface to form a film. After the adhesive is spot-coated and pre-permeated, the next step of interface bonding can be performed as follows: first, precise dosing is achieved by a micro pipette to avoid waste and fiber damage caused by bulk operation; second, the annular and cross-shaped area partition layout is differentially arranged for different mechanical requirements of different parts to improve the mechanical response of the overall patch after bonding; finally, 10 minutes of pre-permeation meets the mechanism requirements of initial penetration and interface bonding, and avoids excessive diffusion.

[0034] When the electrospun round patch substrate in the patch delivery system is evenly distributed with a micro pipette, the adhesive is formed into a circle along the outer edge of the electrospun round patch and a cross in the center of the round patch, thereby obtaining an adhesive patch delivery system; The adhesive, including cyanoacrylate-based adhesive, is prepared 1 to 5 days in advance before use and stored in a space at 4℃.

[0035] Specifically, the cyanoacrylate-based adhesive is prepared 1 to 5 days in advance before use and stored at 4℃. By a longer but controlled storage period, the adhesive slowly undergoes possible trace pre-polymerization or ingredient homogenization process in low temperature, thereby avoiding inconsistencies in spot coating or differences in interface bonding strength due to uneven composition or viscosity fluctuations near the time of use. Cyanoacrylate is easily damp at room temperature and the polymerization reaction is triggered by trace moisture in the air. If it is prepared immediately before use, it may face the problem of rapid viscosity change and short operation window; When the adhesive needs to be applied on the electrospun round patch substrate in the patch delivery system, the present application adopts a micro pipette to form a ring-shaped coating along the outer edge of the round patch and a cross-shaped coating in the center, so that the adhesive is distributed locally with peripheral anchoring and central support, while leaving an uncoated area to maintain the openness of the fiber network, ensuring that the overall patch obtains sufficient adhesion at the boundary to resist possible shear or bending loads; the central cross-shaped layout forms cross-shaped anchor points in the inner area, not only dispersing internal stress and preventing edge warping or center loosening caused by uneven solidification of the outer edge, but also facilitating the preservation of channels in the uncoated area to support subsequent fluid exchange or cell migration functions. In the dot coating process, the total volume is strictly controlled within a small range of 50 μL or less to reduce the shading of the fiber pore structure and the waste of chemical dosage, and to enhance the synergistic effect with the aforementioned low-temperature storage formulation: the precise dispensing of the micro pipette can avoid the spread of local hardened areas to non-target areas caused by excessive accumulation of adhesive, and also reduce the damage to the fiber structure caused by the heat effect during subsequent solidification. The standing pre-permeation stage is maintained for a certain period of time, about 10 minutes, after dot coating. Although this step is not emphasized too much, since the initial activity of the adhesive has been optimized during low-temperature storage, the adhesive can effectively penetrate the fiber surface relief structure through micro-capillary and diffusion action in a short time after dot coating on the patch, laying a solid interface foundation for subsequent solidification or bonding operations.

[0036] A degradable aortic dissection repair patch, comprising: The double-sided structure fiber sheet has a one-sided directional arrangement of fiber structure and a one-sided disordered arrangement of fiber structure; The double-sided structure fiber sheet includes disordered arrangement of fibers obtained when the solvent is stationary, and directional arrangement of fibers obtained after deposition of the collector rotating clockwise; The fiber sheet is processed into a circular patch, and the directional surface is connected to the conveyor through at least four suture stitches; The disordered surface of the patch has a patterned structure formed by a cyanoacrylate adhesive, and the pattern includes a ring-shaped area around the edge of the patch and a cross-shaped area through the center of the patch.

[0037] Specifically, first, the patch adopts a double-sided structure, one side is a directional arrangement of fiber layer, the other side is a disordered arrangement of fiber layer. The directional fibers are formed by continuous deposition on a rotating collector, and the fiber orientation is consistent with the circumferential stress direction of the aorta, which can quickly bear the circumferential tension from the blood flow pulsation after the patch is implanted, effectively preventing the patch from creeping or breaking under high pressure. Compared with traditional disordered fiber materials, this mechanical advantage can significantly reduce the risk of material failure after surgery or during the early implantation stage. Following the technical content of the directional layer, the present application realizes precise control of fiber diameter and porosity by matching the collector speed and polymer solution viscosity, thereby optimizing the synergistic balance of mechanical strength and degradation rate. On the other hand, the disordered fiber layer is obtained spontaneously in the solvent static state, and its multidirectional network structure can promote cell migration and microvessel ingrowth on the tissue side, providing microenvironment support for subsequent endothelialization. At the same time, the randomly interwoven fiber pores are more conducive to bidirectional exchange of nutrients and signal molecules, assisting in the self-repair of the aortic wall. The patch is processed into a circular shape, and the diameter and thickness can be customized according to the patient's aortic orifice. The directional surface is firmly connected to the delivery device by at least four sutures, ensuring that the circumferential arrangement direction of the fibers is strictly aligned with the blood flow principal stress direction when sent into the aortic cavity, avoiding implantation deviation caused by rotation or misplacement. The disordered surface is coated with a cyanoacrylate adhesive and formed into a specific pattern through micro-mold etching or inkjet printing, etc. The closed annular band around the edge of the patch and the cross-shaped band through the center. The annular band can form a continuous and uniform adhesion barrier between the peripheral edge of the patch and the host tissue, effectively preventing blood leakage; the cross-shaped band provides a precise positioning bonding point in the central region, taking into account the shear resistance and tear resistance. This patterning strategy not only reduces the amount of adhesive used, but also reduces the chemical stimulation of the local tissue. The patch is made of electrospinning technology, and the lumen surface is composed of neatly arranged fibers, which is more suitable for blood flow dynamics in the blood vessel and promotes vascular endothelial cell colonization; the basal surface is composed of disordered fibers, which promotes smooth muscle cell colonization. The adhesive biodegradable patch has mechanical strength and flexibility that matches the mechanical properties of natural blood vessel tissue, and can achieve in-situ immediate adhesion of the torn intima and adventitia of the blood vessel.

[0038] Although embodiments of the present application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a degradable aortic dissection repair patch, characterized in that: The following steps are involved: Double-sided fiber sheets were prepared by electrospinning. Polycaprolactone solution was pumped from a syringe and deposited on a drum collector under the action of an electric field to form a fiber membrane. The electrospun sheets are naturally air-dried and then cut into circular patch units through a die-cutting process; The cut patch is placed with the oriented side facing downward on the surface of a prefabricated nickel-titanium alloy delivery device, and the patch is manually sutured to the delivery device using water-soluble sutures to form a patch delivery system; Applying an adhesive uniformly or in spots on the disordered fiber surface of the patch, wherein the adhesive comprises a cyanoacrylate component and the coating pattern comprises an edge annular area and a central cross-shaped area; Sterilizing the patch delivery system and completing system packaging within a specified time after the adhesive is activated; The prepared patch system is inspected for appearance integrity and patch-to-bracket connection strength. Once qualified, it is stored in a sterile, low-temperature environment for future use.

2. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: When the deposition forms the fiber membrane, the deposition time of the polycaprolactone solution is divided into 2 hours, wherein in the first hour, the collector remains stationary and the polycaprolactone solution forms a disordered fiber layer, and in the second hour, the collector rotates clockwise at 1000 r / min to form an ordered fiber layer. After the polycaprolactone solution is deposited for 2 hours, a double-sided electrospun sheet is obtained.

3. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: The solution during the deposition was pumped using a syringe, which was placed on a syringe pump system and propelled at a solvent flow rate of 2000 uL / h. The syringe pump was placed horizontally at a distance of 18.0 cm from the collector.

4. The method for preparing a degradable aortic dissection repair patch according to claim 3, characterized in that: When the solvent flow is pushed forward, a voltage of 16.0-20.0 kV is applied between the injection pump and the collector, and the collector is a barrel made of metal material.

5. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: The method of naturally air-drying the electrospun sheet comprises the following steps: The double-sided electrospun sheet that has completed spinning deposition is peeled off from the collector surface and placed on a non-woven fabric or an inert flat surface; In a clean bench, flatten the electrospun sheet and allow it to spread naturally on a flat surface; The unfolded electrospun sheet was then placed in a dust-free space to cool for 1 hour; After air drying, the electrospun sheet was taken out for a preliminary visual inspection to confirm that there was no obvious liquid attachment, adhesion or wrinkles on the surface before proceeding to the next step.

6. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: The die-cutting process is used to cut the circular patch units, including the following steps: The air-dried electrospun sheet is laid flat on the die-cutting platform and placed in a positioning fixture to maintain the spinning direction; Cutting is completed by manually pressing or mechanically controlling the die cutting head to press down. The diameter of the circular die used for cutting is 10mm. After the cutting is completed, sterile tweezers are used to remove the circular patch unit from the mold, and the qualified patch unit is temporarily placed on the surface of the prefabricated nickel-titanium alloy conveyor to complete the cutting.

7. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: The adhesive is evenly distributed on the base surface of the electrospun disc in the patch delivery system using a micropipette to form a circle along the outer edge of the electrospun disc and a cross in the center of the disc, thereby preparing an adhesive patch delivery system; The adhesive, including the cyanoacrylate-based adhesive, is prepared in advance 1 to 5 days before use and stored in a room at 4°C.

8. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: The adhesive is applied to the disordered fiber surface of the patch by using a micropipette to sequentially drop a cyanoacrylate solution on the edge ring area and the central cross area of ​​the patch, with the total volume of the application controlled within 50 μL. The adhesive solution is allowed to stand for 10 minutes after application to complete pre-infiltration.

9. The method for preparing a degradable aortic dissection repair patch according to claim 1, characterized in that: The step of suturing the patch to the conveyor comprises: The oriented fiber side of the patch is placed downward on the outer surface of the nickel-titanium alloy conveyor, and is sutured to the head, tail, left side and right side of the electrospinning disc respectively with water-soluble sutures. The suturing method is manual puncture fixation.

10. A degradable aortic dissection repair patch, characterized in that: A method for using a degradable aortic dissection repair patch according to any one of claims 1 to 9, comprising: A double-sided structural fiber sheet having a fiber structure with directional arrangement on one side and a fiber structure with disordered arrangement on the other side; The double-sided structural fiber sheet includes randomly arranged fibers obtained when the solvent is left to stand, and oriented fibers obtained after the collector rotates clockwise and deposits; The fiber sheet is processed into a circular patch, the orientation surface of which is connected to the conveyor, and the connection is positioned by sewing at least four sutures; The disordered surface of the patch has a patterned structure formed by a cyanoacrylate adhesive, wherein the pattern includes a ring region surrounding the edge of the patch and a cross region running through the center of the patch.

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