Fiber scaffolds and their preparation methods, fiber scaffold systems and their preparation methods

Abstract

This application discloses a fiber scaffold and its preparation method, a fiber scaffold system and its preparation method, belonging to the field of medical devices. The scaffold has a hollow tubular structure, including an inner fiber layer, a fiber support structure, and an outer fiber layer. The fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer, and the outer fiber layer covers the outer surfaces of the inner fiber layer and the fiber support structure. The fiber porosity of the inner fiber layer is less than or equal to that of the outer fiber layer. The fiber support structure is composed of electrospun fibers and includes annular bodies distributed along the axial direction of the scaffold, with axial spacing between adjacent annular bodies to provide radial support. This application utilizes the annular bodies to provide radial support, while the axial spacing provides deformation space for bending, giving the scaffold both radial stiffness and axial flexibility; the differentiated porosity design is beneficial for cell infiltration and tissue regeneration, making it suitable for vascular interventional therapy.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and in particular to a fiber scaffold and its preparation method, and a fiber scaffold system and its preparation method. Background Technology

[0002] Vascular diseases, particularly coronary atherosclerotic heart disease, are among the leading causes of death worldwide. Percutaneous coronary intervention (PCI) has evolved from simple balloon angioplasty to stent implantation, but simple balloon angioplasty has a high restenosis rate. Biodegradable vascular stents, with their degradability and vascular remodeling capabilities, meet the trend of "intervention without implantation." Biodegradable tissue-engineered vascular stents, combining temporary mechanical support with long-term tissue regeneration guidance, represent a highly promising development direction.

[0003] An ideal vascular stent should possess good biocompatibility, mechanical properties that match the patient's own blood vessels (including bending compliance and radial support), and the ability to promote endothelialization and inhibit intimal hyperplasia. Electrospinning technology can mimic the structure of the natural extracellular matrix, offering significant advantages in the field of tissue-engineered vascular stents. However, existing electrospinning-based vascular stent technologies still have the following shortcomings: First, their bending resistance is insufficient. Existing homogeneous or simple multilayer electrospun stents cannot simulate the three-layer heterogeneous structure of natural blood vessels. After implantation, especially when crossing active areas such as joints, they cannot withstand long-term bending, torsion, and compressive stress, and are prone to fatigue fracture or bending collapse, leading to restenosis or aneurysm formation.

[0004] Second, poor cell infiltration. Traditional electrospun scaffolds have densely packed fibers with pores smaller than cell size, allowing cells to grow only on the scaffold surface and making it difficult for them to migrate inward, thus failing to achieve three-dimensional tissue regeneration.

[0005] Third, poor process integration. Existing fabrication processes struggle to integrate bending-resistant design, controllable pore size structure, fiber orientation, and balloon expansion characteristics into a stable and repeatable process, resulting in insufficient compressibility and balloon expansion adaptability of the stent.

[0006] Therefore, there is an urgent need for a multilayer vascular tissue engineering fiber scaffold and its preparation method that can systematically solve the above-mentioned technical problems, especially the problem of insufficient bending resistance. Summary of the Invention

[0007] This application discloses a fiber scaffold and its preparation method, and a fiber scaffold system and its preparation method, to solve the technical problem of insufficient bending resistance of vascular stents in related technologies.

[0008] To solve the above problems, this application adopts the following technical solution: In a first aspect, embodiments of this application provide a multilayer vascular tissue engineered fiber scaffold, the scaffold having a hollow tubular structure, comprising: Inner fiber layer; A fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer. The fiber support structure includes annular bodies distributed along the axial direction of the support, and there is an axial spacing between adjacent annular bodies. An outer fiber layer, which covers the outer surface of the inner fiber layer and the fiber support structure; Wherein, the fiber porosity of the inner fiber layer is less than or equal to the fiber porosity of the outer fiber layer; The fiber support structure is made of electrospun fibers and is used to provide radial support force.

[0009] Secondly, embodiments of this application provide a method for preparing the multilayer vascular tissue engineered fiber scaffold described in the first aspect, comprising the following steps: Electrospinning is used to form an inner fiber layer on the receiver; The fiber support structure is independently prepared by electrospinning, and the fiber support structure includes a ring-shaped body. The fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer; Electrospinning is used to form an outer fiber layer on the outer surface of the inner fiber layer and the fiber support structure, and the fiber support structure is wrapped between the inner fiber layer and the outer fiber layer.

[0010] Thirdly, embodiments of this application provide a multilayer vascular tissue engineered fiber scaffold system, comprising: The multilayer vascular tissue engineered fiber scaffold described in the first aspect; and A delivery device on which the multilayer vascular tissue engineered fiber scaffold is loaded.

[0011] Fourthly, embodiments of this application provide a method for preparing the multilayer vascular tissue engineered fiber scaffold system described in the third aspect, comprising the following steps: Provide a multilayer vascular tissue engineered fiber scaffold as described in the first aspect; The multilayer vascular tissue engineered fiber scaffold is loaded onto a delivery device to form the multilayer vascular tissue engineered fiber scaffold system.

[0012] The technical solutions adopted in the embodiments of this application can achieve the following beneficial effects: (1) The multilayer vascular tissue engineering fiber scaffold provided in this application provides a three-layer structure by setting an inner fiber layer and a fiber support structure coaxially fitted, and an outer fiber layer covering the outer surface of the inner fiber layer and the fiber support structure. In particular, the fiber support structure includes annular bodies distributed along the axial direction of the scaffold, and there is an axial spacing between adjacent annular bodies, which gives the scaffold excellent radial support strength. When the scaffold is bent significantly, the material on the outer side of the bending radius is stretched and the material on the inner side is compressed. The axial spacing acts as a bending deformation buffer, with the outer gap increasing and the inner gap decreasing, allowing the inner and outer fibers to deform, slide and rearrange freely in the gap area, thereby effectively avoiding stress concentration and preventing the scaffold from bending and collapsing. By setting the axial spacing, this application can use the annular bodies to provide stable radial support force to maintain lumen patency, and can use the gap between adjacent annular bodies to release bending deformation stress to improve bending compliance, thus achieving a synergistic match between radial rigidity and axial compliance. Compared with existing homogeneous or simple multilayer electrospun stents, this application significantly improves the bending resistance and solves the problem that vascular stents are prone to fatigue fracture or bending collapse when crossing joints and other moving parts, thereby reducing the risk of restenosis or aneurysm formation.

[0013] (2) The multilayer vascular tissue engineering fiber scaffold provided in this application has a fiber support structure composed of electrospun fibers and includes annular bodies distributed along the axial direction of the scaffold, which provides stable radial support for the scaffold, effectively maintains lumen patency, prevents elastic recoil of blood vessels, and avoids restenosis.

[0014] (3) The multilayer vascular tissue engineering fiber scaffold provided in this application, by limiting the fiber porosity of the inner fiber layer to be less than or equal to that of the outer fiber layer, makes the packing density of the inner fiber layer of the scaffold greater than or equal to that of the outer fiber layer. Thus, the inner fiber layer has a density not lower than that of the outer fiber layer, which is conducive to the rapid formation of the endothelial cell layer on the lumen surface and reduces thrombus formation. The porous structure of the outer fiber layer facilitates cell adhesion, migration, proliferation and differentiation into the scaffold, accelerating vascular tissue remodeling. At the same time, the porous fiber structure can simulate the natural extracellular matrix, guide the behavior of intravascular cells, and establish a new endothelial layer and smooth muscle layer.

[0015] (4) The multilayer vascular tissue engineering fiber scaffold provided in this application embodiment has an inner fiber layer and a fiber support structure coaxially sleeved, and an outer fiber layer covering the outer surface of the inner fiber layer and the fiber support structure, so that the fiber support structure is sandwiched between the inner and outer layers, and the three form a stable sandwich structure, which can ensure that the multilayer structure does not separate during long-term in vivo service, thus improving the overall reliability of the scaffold. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 This is a structural schematic diagram of an embodiment of this application; Figure 2 yes Figure 1 A cross-sectional view at position AA in the middle; Figure 3 yes Figure 1 A cross-sectional view at position BB in the middle; Figure 4 This is a schematic diagram of the external structure of the fiber support structure adopted in the embodiments of this application (a); Figure 5 This is a schematic diagram of the external structure of structure (b) adopted in the embodiment of this application; Figure 6 This is a schematic diagram of the external structure of structure (c) used in the fiber support structure of this application embodiment; Figure 7 yes Figure 6 Schematic diagram of the layout of the central support rod; Figure 8 This is a schematic diagram of the external structure of the fiber support structure in the embodiments of this application when the circumferential contour of the ring body is sawtooth-shaped; Figure 9 This is a schematic diagram of the external structure of the fiber support structure in the embodiments of this application when the circumferential contour of the ring body is W-shaped; Figure 10 This is a schematic diagram illustrating the cross-orientation of fibers in an embodiment of this application; Figure 11 This is a schematic diagram illustrating the random orientation of fibers in an embodiment of this application; Figure 12 This is a schematic diagram of the spinning of the inner fiber layer in an embodiment of this application; Figure 13 This is a schematic diagram of the spinning of the outer fiber layer in an embodiment of this application; Figure 14 (a) Figure 14 (b) Figure 14 (c) Figure 14 (d) Figure 14 (e) is a schematic diagram of the working process of the multilayer vascular tissue engineered fiber scaffold in the embodiments of this application; Figure 15These are the axial bending compliance test results of Embodiment 2.1 and Comparative Example 1 of this application.

[0018] In the diagram: 10, fibrous scaffold; 101, inner fibrous layer; 102, annular body; 103, outer fibrous layer; 104, connecting rod; 20, balloon catheter; 30, balloon; 40, blood vessel; 50, guidewire; 60, vascular sheath; 70, spinning syringe; 80, receiver. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be described in detail below. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. Based on the embodiments in this application, all other implementation methods obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0020] The terms "first," "second," etc., used in the specification and claims of this application are used to distinguish similar objects and are not used to describe a specific order or sequence. It should be understood that such use of terms can be interchanged where appropriate so that embodiments of this application can be implemented in orders other than those illustrated or described herein, and the objects distinguished by "first," "second," etc., are generally of the same class and the number of objects is not limited; for example, a first object can be one or more. Furthermore, in the specification and claims, "and / or" indicates at least one of the connected objects, and the character " / " generally indicates that the preceding and following objects are in an "or" relationship.

[0021] Electrospun vascular stents in related technologies are mostly homogeneous tubular structures or simple multilayer structures. Their dense fiber packing and low porosity result in excessive overall rigidity, making them unable to withstand cyclic tensile, compressive, and torsional loads at 40° bends or joints, easily leading to bending, collapse, or fatigue fracture. Furthermore, the pore size of the homogeneous structure is much smaller than the cell size, allowing cells to grow only on the stent surface and preventing inward migration, thus limiting three-dimensional tissue regeneration. In addition, the radial support function and axial bending compliance of existing stents are mutually restrictive; there is an inherent contradiction between radial support and axial bending flexibility, making it difficult to simultaneously achieve both.

[0022] Therefore, this application proposes a fiber scaffold and its preparation method, a fiber scaffold system and its preparation method, which are described below in conjunction with the appendix. Figures 1 to 15 This application provides a detailed description of a fiber scaffold and its preparation method, as well as a fiber scaffold system and its preparation method, through specific embodiments and application scenarios.

[0023] I. Example: Example 1:

[0024] Please see Figures 1 to 3 This application proposes a multilayer vascular tissue engineering fiber scaffold, which comprises a three-layer structure consisting of an inner fiber layer 101, a fiber support structure, and an outer fiber layer 103. The inner fiber layer 101 and the fiber support structure are coaxially sleeved, and the outer fiber layer 103 covers the outer surfaces of the inner fiber layer 101 and the fiber support structure. The fiber porosity of the inner fiber layer 101 is less than or equal to the fiber porosity of the outer fiber layer 103, resulting in a density of the inner fiber layer 101 that is not lower than that of the outer fiber layer 103. The density of the inner fiber layer 101 facilitates rapid endothelialization and antithrombosis, while the porous structure of the outer fiber layer 103 facilitates cell infiltration and tissue remodeling. The fiber support structure is composed of electrospun fibers and includes annular bodies 102 distributed along the axial direction of the stent. Adjacent annular bodies 102 are spaced axially, and the gaps formed by these axial spacings act as buffer zones for bending deformation. This allows the outer gap to increase and the inner gap to decrease when the stent bends, enabling the inner and outer fibers to slide and rearrange freely within the gap region, thereby releasing bending stress and preventing localized stress concentration. Simultaneously, the annular bodies 102 provide stable radial support to resist the elastic recoil of the vessel 40. Thus, this stent achieves a synergistic balance between radial support rigidity and axial bending flexibility, ensuring luminal patency while adapting to the natural curvature of the vessel 40.

[0025] Please see Figure 4 In some embodiments, the fiber support structure includes a plurality of independent annular bodies 102 spaced apart along the axial direction of the stent. It is understood that the key to this structure, with the multiple independent annular bodies 102 spaced apart along the axial direction, is to ensure that the radial support function and the axial bending function are independent and do not interfere with each other. The multiple annular bodies 102 form segmented support points in the axial direction, jointly resisting the elastic recoil of the blood vessel 40 and maintaining lumen patency. The axial spacing between adjacent annular bodies 102 serves as a buffer zone for bending deformation. When the stent bends with the blood vessel 40, the gap on the outer side of the bend increases, and the gap on the inner side decreases, allowing the inner and outer fibers to slide and rearrange freely within the gap area, thereby significantly releasing bending stress and avoiding bending or fatigue fracture caused by local stress concentration. Thus, the structure achieves a balance between rigid support and flexible compliance in terms of mechanical properties; the annular body 102 provides the stent with sufficient radial stiffness to resist the collapse of the blood vessel 40, while the gap provides axial bending compliance to adapt to the natural bending of the blood vessel 40; the two complement each other and effectively overcome the technical contradiction of traditional continuous annular or homogeneous tubular stents being either too rigid and easy to bend or too soft and insufficiently supportive.

[0026] Please see Figure 5In some embodiments, the fiber support structure includes a helical ring 102, which can be a continuous structure or a discontinuous structure with breaks. It is understood that the helical ring 102 extends axially along the stent, with an axial spacing between adjacent helical coils. The helical ring 102 provides continuous and uniform radial support force, resisting elastic recoil of the vessel 40 and maintaining luminal patency. The axial spacing acts as a buffer zone for bending deformation; when the stent bends, the gap on the outer side increases and the gap on the inner side decreases, allowing the inner and outer fibers to slip and rearrange within the gap area, thereby alleviating bending stress concentration and preventing stent bending or fatigue fracture. A continuous helical structure avoids axial support blind spots, resulting in a more uniform distribution of radial support force; a discontinuous structure with breaks provides additional local flexibility at the break points to adapt to more complex vessel 40 bending morphologies. Therefore, this structure also balances the continuity of radial support with compliance with axial bending.

[0027] Please see Figure 6 , Figure 7 In some embodiments, the fiber support structure includes multiple annular bodies 102 spaced apart along the axial direction of the support and multiple sets of connecting rods 104. Each set of connecting rods 104 is disposed between two adjacent annular bodies 102, and the two sets of connecting rods 104 adjacent along the axial direction are staggered in the circumferential direction. It is understood that this structure adds connecting rods 104 to the spaced annular bodies 102 to form a truss-type reinforcement system. The annular bodies 102 themselves provide segmented radial support to resist the elastic recoil of the blood vessels 40; the connecting rods 104 span the gaps between the annular bodies 102, connecting adjacent annular bodies 102 into a unified load-bearing structure. Under radial compression, the connecting rods 104 can transfer loads between the annular bodies 102, enabling the support structure to bear load collaboratively, thereby improving radial compressive strength. Under torsional loads, the connecting rods 104 can restrict the relative circumferential slippage between the annular bodies 102, enhancing torsional stability. The adjacent sets of connecting rods 104 are staggered in the circumferential direction, making the distribution of the connecting rods 104 more uniform in the circumferential direction. This avoids excessive concentration or complete absence of support force at specific circumferential locations, thus achieving balanced circumferential support. At the same time, the axial spacing between the annular bodies 102 is maintained, serving as a buffer zone for bending deformation. This allows the inner and outer fibers to deform freely within the gap area, thereby enhancing torsional and fatigue resistance while maintaining good axial bending flexibility. This structure is particularly suitable for vascular sites 40 that are subjected to combined bending, torsion, and pulsating pressure, such as the aortic arch, popliteal artery, or transarticular vessels 40.

[0028] In some embodiments, the fiber support structure includes a plurality of annular bodies 102 spaced apart along the axial direction of the support and a plurality of sets of connecting rods 104, each set of connecting rods 104 comprising 1-8 connecting rods 104, the connecting rods 104 being selected from straight rods, corrugated rods, or diagonal rods. The number of connecting rods 104 can be set as needed.

[0029] Please see Figure 8 , Figure 9 In some embodiments, when the fiber support structure includes multiple independent rings 102, such as the rings 102 in structures (a) or (c), the circumferential contour of the rings 102 is circular or wavy. The wavy shape includes sine waves, sawtooth shapes, W-shapes, etc. It is understood that the wavy rings 102, while maintaining an overall circular contour, have wavy undulations in their circumferential edges. This undulating structure increases the contact area and mechanical interlocking between the rings 102 and the inner and outer fibers, thereby improving interlayer bonding strength. Simultaneously, the undulating structure allows stress to be dispersed and transferred along the wavy path when the support is bent, reducing local stress concentration and further improving bending resistance and fatigue life. When the fiber support structure is a spiral ring 102, the circumferential contour of the spiral path of the spiral ring 102 can also be wavy. As long as the overall structure is an independent ring 102 or a spiral ring 102, the wavy design of its circumferential contour falls within the protection scope of this application.

[0030] In some embodiments, when the fiber support structure is (a) or (c), the width of the annular body 102 along the stent axial direction is 0.5-10 mm, and the axial spacing between adjacent annular bodies 102 is 0.2-8 mm; when the fiber support structure is (b), the width of the spiral coil of the helical annular body 102 along the stent axial direction is 0.5-10 mm, and the axial spacing between adjacent spiral coils is 0.2-8 mm, which is the pitch. It is understood that the width of the annular body 102 determines the length of the radial support area provided by a single annular body 102. A width that is too small (less than 0.5 mm) will result in a narrow support point, high local pressure, and potential damage to the intima of the blood vessel; a width that is too large (greater than 10 mm) will result in excessive axial stiffness of the stent and decreased bending compliance. The axial spacing determines the gap length between adjacent support points. Too small a spacing (less than 0.2 mm) will result in an excessively narrow gap area, insufficient buffer zone for bending deformation, and an overall stiff stent. Too large a spacing (greater than 8 mm) will result in an excessively long gap area, potentially causing local collapse or excessive intimal hyperplasia of the vessel 40 at the gap. Furthermore, within a width range of 0.5 mm to 10 mm and a spacing range of 0.2 mm to 8 mm, the stent can provide sufficient radial support while retaining ample space for bending deformation, adapting to the mechanical requirements of different locations within the vessel 40. In practical applications, the mechanical properties of the stent can be controlled by adjusting the ratio of width to axial spacing: for vessels 40 requiring higher radial support, the width of the annular body 102 can be appropriately increased while the axial spacing decreases; for vessels 40 requiring good bending compliance, the width of the annular body 102 can be appropriately decreased while the axial spacing increases. Those skilled in the art can select an appropriate combination of width and spacing within the above range based on the diameter, degree of curvature, and pulsating pressure of the target vessel 40. The specific number of annular bodies 102 can be designed based on the length of the fiber stent 10, the width of the annular bodies 10, and the axial spacing.

[0031] In some embodiments, the width of the annular body 102 is greater than or equal to the axial spacing between adjacent annular bodies 102.

[0032] In some embodiments, the fiber porosity of the inner fiber layer 101 is 30%-95%, and the fiber porosity of the outer fiber layer 103 is 40%-95%; the fiber porosity of the fiber support structure is 20%-80%, and the fiber porosity of the fiber support structure is less than or equal to the fiber porosity of the inner fiber layer 101.

[0033] In some embodiments, the fiber porosity of the inner fiber layer 101 is 55%-75%, the fiber porosity of the outer fiber layer 103 is 55%-75%, and the fiber porosity of the fiber support structure is 40%-50%. Furthermore, the fiber porosity of the inner fiber layer 101 is less than that of the outer fiber layer 103, and the fiber porosity of the fiber support structure is less than that of the inner fiber layer 101. For example, the fiber porosity of the inner fiber layer 101 can be selected as 60%, the fiber porosity of the outer fiber layer 103 can be selected as 70%, and the fiber porosity of the fiber support structure can be selected as 45%. Alternatively, the fiber porosity of the inner fiber layer 101 can be selected as 55%, the fiber porosity of the outer fiber layer 103 can be selected as 75%, and the fiber porosity of the fiber support structure can be selected as 40%. Those skilled in the art can select specific values ​​within the above ranges according to actual mechanical and biological requirements. Understandably, the lower porosity of the fibrous support structure indicates a denser fiber packing and a higher fiber content per unit volume, thus giving it a higher compressive modulus and radial support strength. This allows it to serve as the main mechanical load-bearing layer of the scaffold, effectively resisting the elastic recoil of the vessel and maintaining luminal patency. Simultaneously, the lower porosity also means that the average pore size of the fibrous support structure itself is smaller, which can limit the excessive migration and proliferation of vascular smooth muscle cells into the scaffold, reducing the risk of restenosis. The porosity of the inner fibrous layer 101 ensures sufficient density to facilitate rapid endothelial cell colonization and reduce thrombus formation while retaining some pores for nutrient exchange. The high porosity of the outer fibrous layer 103 forms a loose macroporous structure, facilitating the migration and infiltration of fibroblasts and smooth muscle cells into the scaffold, promoting the growth of three-dimensional tissues. The low porosity of the fibrous support structure gives it high density and compressive strength, providing reliable radial support for the scaffold. The porosity of the three layers exhibits a gradient distribution from the inside out, with the inner layer having the lowest porosity and the outer layer the highest, achieving a layered synergy between mechanical support and tissue regeneration function.

[0034] In some embodiments, the average pore size of the inner fiber layer 101 is 0.5um-100um, the average pore size of the outer fiber layer 103 is 0.5um-200um, and the average pore size of the fiber support structure is 0.5um-100um; and the average pore size of the fiber support structure is less than or equal to the average pore size of the inner fiber layer 101, and the average pore size of the inner fiber layer 101 is less than or equal to the average pore size of the outer fiber layer 103. Understandably, the average pore size of the fibrous support structure is no larger than that of the inner fibrous layer (i.e., the smallest or equal), resulting in the densest fiber packing and providing the strongest mechanical support. The average pore size of the inner fibrous layer 101 is greater than or equal to the average pore size of the fibrous support structure, and less than or equal to the average pore size of the outer fibrous layer 103, allowing nutrient diffusion while preventing platelet infiltration. The average pore size of the outer fibrous layer 103 is the largest (or equal to the average pore size of the inner fibrous layer 101), typically larger than the cell size, facilitating cell migration into the scaffold. The design can be tailored to the cell size at different locations within the vessel 40. Through these pore size differences, the scaffold achieves a functional transition from the inside out: the inner layer inhibits thrombus formation, the middle layer provides mechanical support, and the outer layer guides tissue ingrowth; these three layers work together to promote vessel 40 repair. The actual selection of scaffold values ​​should satisfy the aforementioned average pore size relationships.

[0035] In some embodiments, the average pore size of the inner fiber layer 101 is 15µm-25µm, the average pore size of the outer fiber layer 103 is 20µm-40µm, and the average pore size of the fiber support structure is 15µm-25µm. In actual selection, the average pore size of the fiber support structure should be less than or equal to the average pore size of the inner fiber layer 101, while simultaneously satisfying that the average pore size of the inner fiber layer 101 should be less than or equal to the average pore size of the outer fiber layer 103. For example, the average pore size of the inner fiber layer 101 can be selected as 20µm, the average pore size of the outer fiber layer 103 can be selected as 30µm, and the average pore size of the fiber support structure can be selected as 15µm. Alternatively, the average pore size of the inner fiber layer 101 can be selected as 25µm, the average pore size of the outer fiber layer 103 as 35µm, and the average pore size of the fiber support structure as 20µm. Alternatively, when the average pore size of the inner fiber layer 101 is equal to the average pore size of the outer fiber layer 103, for example, the average pore size of the inner fiber layer 101 is selected as 25 μm, the average pore size of the outer fiber layer 103 is selected as 25 μm, and the average pore size of the fiber support structure is selected as 15 μm.

[0036] In some embodiments, the average fiber diameter of the inner fiber layer 101 is smaller than that of the outer fiber layer 103, and the average fiber diameter of the fiber support structure is smaller than or equal to that of the inner fiber layer 101. It is understood that the trend of the average fiber diameter variation is basically consistent with the trend of the average pore size variation (average pore size of the fiber support structure ≤ average pore size of the inner fiber layer 101 ≤ average pore size of the outer fiber layer 103). The difference in average fiber diameter further reflects the functional division of the scaffold layers at the microscopic level: the fibers of the inner fiber layer 101 are finer, which is conducive to rapid endothelialization; the average fiber diameter of the fiber support structure is not greater than that of the inner fiber layer 101 (i.e., the finest or as fine as the inner layer), forming a dense structure to provide mechanical support; the fibers of the outer fiber layer 103 are coarser, constructing loose channels to promote tissue ingrowth. These three elements work together to achieve a synergistic effect of antithrombosis, load-bearing capacity, and promotion of repair.

[0037] In this application, the average fiber diameter, average pore size, and fiber porosity among the inner fiber layer 101, the fiber support structure, and the outer fiber layer 103 are related as follows: The average fiber diameter of the fiber support structure is less than or equal to the average fiber diameter of the inner fiber layer 101, the average pore size of the fiber support structure is less than or equal to the average pore size of the inner fiber layer 101, and the fiber porosity of the fiber support structure is less than or equal to the fiber porosity of the inner fiber layer 101, thereby achieving the highest compressive modulus and radial support strength. The average fiber diameter of the inner fiber layer 101 is between that of the fiber support structure and the outer fiber layer 103 (i.e., greater than or equal to that of the fiber support structure and less than that of the outer fiber layer 103), and its average pore size is greater than or equal to that of the fiber support structure and less than or equal to that of the outer fiber layer 103. The average pore size of the inner fibrous layer 103 has a fiber porosity greater than or equal to that of the fibrous support structure and less than or equal to that of the outer fibrous layer (i.e., between the two, with the endpoints being acceptable). This allows for the formation of a moderately dense luminal surface, facilitating rapid endothelial cell migration and reducing thrombus formation. The outer fibrous layer 103 has the largest average fiber diameter, and its average pore size is greater than or equal to the average pore size of the inner fibrous layer 101 (i.e., the largest or equal). Furthermore, its fiber porosity is greater than or equal to that of the inner fibrous layer 101 (i.e., the highest or equal). This forms a loose, porous structure, which facilitates the migration, proliferation, and differentiation of vascular wall cells into the scaffold.

[0038] It is understandable that, under similar fiber stacking methods, the average fiber diameter is positively correlated with the average pore size and porosity: the finer the fiber, the smaller the gaps between fibers, and the lower the pore size and porosity; the coarser the fiber, the larger the gaps between fibers, and the higher the pore size and porosity. This application utilizes this correlation to simultaneously achieve differentiated distributions of pore size and porosity by selecting different fiber diameters in each layer, enabling functional differentiation in the microstructure of the scaffold from the inner cavity to the outer wall.

[0039] In some embodiments, the thickness of the inner fiber layer 101 is 5um-100um, the thickness of the outer fiber layer 103 is 5um-100um, and the radial thickness of the annular body 102 is 10um-200um.

[0040] In some embodiments, the inner fiber layer 101 has a thickness of 20um-50um, the outer fiber layer 103 has a thickness of 15um-30um, and the annular body 102 has a radial thickness of 50um-100um.

[0041] Please see Figure 10 In some embodiments, the inner fiber layer 101 and / or the outer fiber layer 103 are composed of circumferentially cross-oriented fibers. It is understood that circumferential cross-orientation refers to the fibers being arranged primarily along the circumference of the stent and intersecting each other to form a circumferentially reinforced network structure. This orientation imparts high tensile strength to the inner and outer fiber layers 103 in the circumferential direction, allowing them to stretch uniformly circumferentially during balloon 30 expansion, avoiding longitudinal tearing; simultaneously, the circumferential cross-structure provides good radial elastic recovery, enabling the stent to adhere tightly to the vessel wall after expansion, reducing stent retraction and vessel 40 elastic rebound.

[0042] Please see Figure 10 , Figure 11 In some embodiments, the fibers of the fiber support structure have a circumferentially cross-oriented structure or a random orientation structure. It is understood that a circumferentially cross-oriented structure refers to fibers mainly arranged circumferentially along the support and intersecting each other. This orientation can improve the circumferential tensile strength and radial compressive modulus of the annulus 102, allowing it to expand uniformly during the expansion of the balloon 30. A random orientation, on the other hand, imparts isotropic mechanical properties to the annulus 102, suitable for scenarios where strength requirements in a specific direction are not high. By adjusting the rotational speed of the receiver 80 during the electrospinning process, both of these orientation structures can be obtained within the same material system.

[0043] The circumferential cross-orientation described in this application refers to the arrangement of fibers primarily along the circumferential direction of the tubular support, with adjacent fibers or different fiber layers forming a mutually intersecting and interwoven network structure. The cross-orientation angle is typically 10°-90°; for example, the cross-orientation angle can be 30°, 45°, 60°, or 90°. This orientation can be achieved by controlling the reciprocating rotation of the receiver 80 during the electrospinning process or by using a multi-angle nozzle.

[0044] In some embodiments, the proximal and / or distal ends of the multilayer vascular tissue engineered fiber scaffold are provided with radiopaque markers. It is understood that the radiopaque markers may be made of platinum rings, tantalum wires, or polymer materials containing barium sulfate or bismuth trioxide. Under X-ray fluoroscopy, the radiopaque markers can accurately indicate the delivery and release position of the scaffold, facilitating the operator's assessment of whether the scaffold completely covers the lesion, whether displacement or retraction has occurred. The radiopaque markers may be sewn onto the annular body 102, or may be fitted as a separate annular structure onto or at the end of the scaffold annular body 102. Example 2:

[0045] This application provides a method for preparing a multilayer vascular tissue engineered fiber scaffold, comprising the following steps: An inner fiber layer 101 is formed on the receiver 80 using electrospinning. (See [link to documentation]). Figure 12 ; The fiber support structure is independently prepared by electrospinning, and the fiber support structure includes a ring body 102. The fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer 101; Electrospinning is used to form an outer fiber layer 103 on the outer surface of the inner fiber layer 101 and the fiber support structure. The fiber support structure is then sandwiched between the inner fiber layer 101 and the outer fiber layer 103. (See also...) Figure 13 Understandably, this method involves first preparing the inner fiber layer 101 and the fiber support structure independently, then coaxially combining them, and finally achieving coating and fixation through outer electrospinning. Independent preparation allows the fiber support structure to be cut, screened, or pre-treated (e.g., dimensional trimming, surface modification) before being assembled, avoiding interference with the inner fiber layer 101 during continuous spinning. During outer electrospinning, some fibers can pass through the pores of the ring 102 and the gaps in the inner fiber layer 101, forming a mechanical interlock, thereby enhancing the interlayer bonding strength. This process is compatible with various polymer materials, and the process parameters of each step can be independently optimized, exhibiting good operability and repeatability.

[0046] In some embodiments, the process further includes an annealing heat treatment step on the fiber support structure, wherein the annealing heat treatment temperature is higher than the glass transition temperature of the material constituting the annulus 102 and lower than the melting temperature of the material constituting the annulus 102; the annealing heat treatment is performed in any one or a combination of two of the following stages: (i) Before the fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer 101, the fiber support structure is annealed separately. (ii) After the fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer 101 and before the outer fiber layer 103 is formed, the inner fiber layer 101 on which the fiber support structure is sleeved is annealed together. (iii) After the outer fiber layer 103 is formed, the inner fiber layer 101, the fiber support structure, and the outer fiber layer 103 are annealed as a whole. It is understood that the timing of the annealing heat treatment can be selected according to the material characteristics and process requirements. Method (i) is suitable for scenarios where the material of the inner fiber layer 101 or the outer fiber layer 103 is heat-sensitive and not suitable for prolonged heating. Individual annealing can independently strengthen the support structure without affecting other layers. Method (ii) can cause local melting and adhesion at the contact interface between the inner fiber layer 101 and the fiber support structure while fixing the support structure, thereby improving the interlayer bonding strength. Method (iii) completes the overall annealing in one go, which simplifies the process and is suitable for situations where the annealing temperature is higher than the glass transition temperature of all layers, or the annealing temperature is between the glass transition temperatures of the fiber support structure layer and the inner fiber layer 101 and the outer fiber layer 103. Regardless of the method used, annealing can cause the fiber intersections of the ring body 102 to melt and connect, increasing the fiber crystallinity, thereby enhancing the compressive modulus, creep resistance, and fatigue life of the ring body 102. At the same time, it can reliably fix the support structure to the inner layer surface, preventing slippage or misalignment during service.

[0047] In some embodiments, the step of independently preparing the fiber support structure includes: when the fiber support structure is a plurality of independent rings 102, preparing tubular fibers by electrospinning, and then cutting the tubular fibers into rings 102; when the fiber support structure is a helical ring 102, electrospinning is used, and while the receiver 80 rotates, the needle moves back and forth along the axial direction of the receiver 80 to directly form a helical ring 102, and then it is cut into segments according to the required number of helical turns. It is understood that the method of tubular electrospinning and cutting can obtain independent rings 102 of uniform size in batches, which is efficient and has good dimensional consistency; while the method of directly spinning helical rings 102 by reciprocating needle movement can avoid the disruption of helical continuity caused by cutting. Regardless of the method, the independent preparation of the fiber support structure can be achieved, which is convenient for subsequent fitting and covering, and is convenient for mass production. The cut annular bodies 102 can be selected in different widths and quantities as needed, and the cuts can be trimmed before fitting to eliminate edge burrs or loose fibers caused by cutting, ensuring that the axial arrangement is neat and the gaps are uniform after fitting.

[0048] In some embodiments, the electrospinning parameters include: a voltage applied to the needle ranging from 0 kV to +50 kV, a voltage applied to the receiver 80 ranging from 0 kV to -30 kV, a distance between the needle and the receiver 80 ranging from 5 cm to 25 cm, a spinning solution propulsion speed ranging from 0.5 to 8 mL / h, a receiver 80 rotation speed ranging from 50 rpm to 20,000 rpm, a spinning ambient temperature ranging from 15°C to 45°C, and a humidity ranging from 30% to 70%. It is understood that the above parameters collectively affect the electric field strength, jet stretching degree, solvent evaporation rate, and fiber deposition morphology during the electrospinning process. Within this parameter range, an electrospun fiber layer with uniform fiber morphology, controllable orientation, and adjustable porosity can be obtained.

[0049] In some embodiments, the electrospinning uses a spinning syringe with a needle specification of 15G to 30G.

[0050] In some embodiments, by increasing the rotation speed of receiver 80 to above 500 rpm, fibers are wound around receiver 80 at a certain orientation angle to form an oriented fiber structure; by controlling the rotation speed of receiver 80 and the horizontal movement speed of needle, cross-fiber structures with different orientation angles can be prepared; when using a low-speed rotation below 500 rpm, randomly oriented fibers can be prepared.

[0051] In some embodiments, the solution used for electrospinning has a mass / volume concentration of 6% to 30%, that is, 6g to 30g of solute dissolved in 100mL of solvent.

[0052] In some embodiments, the solvent used for electrospinning is selected from one or more of dichloromethane, chloroform, acetone, ethyl acetate, dimethylacetamide, dimethyl sulfoxide, and hexafluoroisopropanol.

[0053] In some embodiments, the solvent used for electrospinning is hexafluoroisopropanol (HFIP), or a mixed solution of dichloromethane (DCM) and dimethylformamide (DMF), exemplarily in a volume ratio of DCM to DMF of 6:4, 7:3, 8:2, or 9:1. It is understood that HFIP has excellent solubility for many bioabsorbable polymers (such as polylactic acid and polycaprolactone) and a moderate evaporation rate, making it suitable for preparing uniform fibers. In the mixed solvent of DCM and DMF, DCM is a volatile solvent, and DMF is a high-boiling-point solvent. The evaporation rate of the spinning solution can be controlled by adjusting their ratio: a higher proportion of DCM results in faster solvent evaporation and a denser fiber surface; a higher proportion of DMF results in slower evaporation and the potential formation of a porous structure on the fiber surface.

[0054] In some embodiments, the inner fiber layer 101, the outer fiber layer 103, and the fiber support structure are made of the same or different materials, and are all selected from one or more of bioabsorbable polymers, non-bioabsorbable materials, and biological components. It is understood that the aforementioned materials are the solutes in the electrospinning solution, which dissolve in the solvent and form fibers through electrospinning. After the solvent evaporates, the solutes are deposited and solidified, ultimately forming each fiber layer. The three layers can be made of the same material to simplify the process and ensure interlayer compatibility; they can also be different to allow for the selection of different materials based on the functional requirements of each layer (e.g., the inner layer requires rapid endothelialization, the middle layer requires high-strength support, and the outer layer requires tissue ingrowth promotion). Bioabsorbable polymers can gradually degrade in vivo and are eventually replaced by new tissue; non-bioabsorbable materials are suitable for scenarios requiring long-term mechanical support; biological components can mimic the natural extracellular matrix, actively promoting cell adhesion and proliferation. Through material selection and combination, the degradation cycle, mechanical properties, and bioactivity of the scaffold can be flexibly controlled.

[0055] In some embodiments, the bioabsorbable polymer is selected from one or more of polylactic acid, polyglycolic acid, polymalonolactone, polydioxanone, polytrimethylol carbonate, poly(4-hydroxybutyrate), polyesteramide, polyurethane, polyethylene glycol, polyvinylpyrrolidone and its copolymers, wherein the polylactic acid includes one or more of poly-L-lactic acid, poly-D-lactic acid, and poly-D,L-lactic acid.

[0056] In some embodiments, the non-biological absorbent material is selected from one or more of polypropylene, polyethylene, polyethylene terephthalate, polytetrafluoroethylene, polyaryl ether ketone, polyamide, fluorinated ethylene propylene copolymer, polybutylene, and polysiloxane.

[0057] In some embodiments, the biological component is selected from one or more of hyaluronic acid, collagen, gelatin, alginate, pectin, and cellulose.

[0058] In some embodiments, the materials constituting the inner fibrous layer 101, the outer fibrous layer 103, and the fibrous support structure are bioabsorbable polymers with a degradation period of 6 to 24 months in vivo. It is understood that in the initial stage (0-3 months) after stent implantation, the stent primarily provides mechanical support to prevent elastic recoil of the blood vessel 40; in the middle stage (3-12 months), with the formation of the new intima and smooth muscle layer, the stent begins to gradually degrade, and the mechanical support is provided by the newly formed tissue; in the later stage (12-24 months), most of the stent is absorbed, and the blood vessel 40 regains its original elasticity and contractile function. By selecting polymers with different degradation rates or adjusting the copolymer ratio, the tissue healing cycle at different sites of the blood vessel 40 can be accurately matched.

[0059] It should be noted that the technical effects achieved in this application are mainly determined by the three-layer structure of the multilayer vascular tissue engineered fiber scaffold and their interrelationships, rather than by specific electrospinning process parameters. Specifically, the inner fiber layer 101 is coaxially sleeved with the fiber support structure, and the outer fiber layer 103 covers the outer surfaces of the inner fiber layer 101 and the fiber support structure. The fiber porosity of the inner fiber layer 101 is less than or equal to that of the outer fiber layer 103, and there is an axial spacing between adjacent annular bodies 102. These structural features collectively endow the scaffold with mechanical properties that balance radial support and axial bending compliance. These effects are inherent properties of the scaffold structure. As long as the structural features of the scaffold in this application are present, regardless of the specific spinning parameters (such as voltage, receiving distance, propulsion speed, ambient temperature and humidity), essentially the same technical effects can be obtained. Therefore, the scaffold structure protected by this application has broad process adaptability. The spinning parameters listed in different embodiments are merely exemplary preferred ranges and not essential for achieving the purpose of this invention. Within the above-described structural framework, those skilled in the art can flexibly adjust the spinning process according to specific materials and production conditions, all of which fall within the scope of protection of this application.

[0060] The technical solution of this application will be further described in detail below with reference to specific embodiments. The following embodiments are for illustrative purposes only and do not constitute a limitation on the scope of protection of this application. Example 2.1:

[0061] 2.1.1 Support Structure This embodiment provides a multilayer vascular tissue engineered fiber scaffold, which has a hollow tubular structure, a total length of 37 mm, and a nominal diameter of 3 mm.

[0062] Inner fiber layer 101: Made of polylactic acid (PLLA) by electrospinning, the fibers are circumferentially cross-oriented, and the average fiber diameter is 1μm-3μm. The inner fiber layer 101 has a thickness of 30μm, a porosity of 60%, and an average pore size of 15μm.

[0063] Fiber support structure: Structure (a) is adopted, namely, multiple independent rings 102 are arranged at intervals along the axial direction of the support. The rings 102 are composed of L-polylactic acid (PLLA) electrospun fibers, with random orientation and an average fiber diameter of 0.5μm-3μm. Each ring 102 has an axial width of 2mm, and the axial spacing between adjacent rings 102 is 1.5mm, with a total of 11 rings 102. The radial thickness of the rings 102 is 100μm, the porosity is 50%, and the average pore size is 15μm.

[0064] Outer fiber layer 103: Made by electrospinning a mixture of polylactic acid (PLLA) and gelatin (mass ratio 8:2), with fibers arranged in a circumferential cross-orientation and an average fiber diameter of 2μm-5μm. The outer fiber layer 103 has a thickness of 20μm, a porosity of 60%, and an average pore size of 30μm.

[0065] 2.1.2 Preparation method Step S10: Prepare the inner fiber layer 101 Polylactic acid (PLLA) was dissolved in a mixed solvent of dichloromethane and dimethylformamide (DCM:DMF = 7:3, volume ratio) to prepare a spinning solution with a mass-volume concentration of 13%. The spinning injector 70 used an 18G stainless steel needle, applying a +25kV voltage, while the receiver 80 was applied with a -15kV voltage. The distance between the needle and receiver 80 was 15cm, and the spinning solution was propelled at a speed of 4.25mL / h. The receiver 80 was a 4mm diameter stainless steel receiver, and the spinning speed was 10000rpm. The ambient temperature was 30℃, and the humidity was 50%. The spinning time was 3 minutes, forming an inner fiber layer 101 on the receiver 80.

[0066] Step S20: Independently prepare fiber support structure Polylactic acid (PLLA) was dissolved in a mixture of dichloromethane and dimethylformamide (DCM:DMF = 8:2, volume ratio) to prepare a spinning solution with a mass-volume concentration of 13%. Using the same spinning injector 70, voltage, distance, and feed speed as in step S10, and with the receiver 80 rotating at 200 rpm, tubular fibers were spun on a receiver 80 with a diameter of 4.2 mm for 6 minutes. The tubular fibers were removed from the receiver 80 and cut into 11 rings 102 with a width of 2 mm. The rings 102 were placed in a vacuum oven and heated to 100°C at a rate of 3°C / min under nitrogen protection, held at that temperature for 2 hours, and then allowed to cool naturally to complete individual annealing.

[0067] Step S30: Install the fiber support structure Eleven annealed annular bodies 102 are sequentially and coaxially fitted onto the outer surface of the inner fiber layer 101, with a spacing of 1.5 mm between adjacent annular bodies 102. The positions are adjusted to ensure even distribution.

[0068] Step S40: Form the outer fiber layer 103 A mixture of polylactic acid (PLLA) and gelatin (8:2) was dissolved in hexafluoroisopropanol (HFIP) to prepare a spinning solution with a mass-volume concentration of 13%. Using the same electrospinning parameters as in step S10, spinning was continued for 2 minutes on the outer surface of the inner fiber layer 101, which was covered with the annular body 102, to form an outer fiber layer 103 that completely covered the annular body 102. The spun scaffold was then removed from the receiver 80 to obtain the final multilayer vascular tissue-engineered fiber scaffold 10. Example 2.2:

[0069] The difference between this embodiment and Embodiment 1 is that the fiber support structure adopts structure (b), namely, a spiral ring 102, which is a continuous structure. Everything else is the same as in Embodiment 1.

[0070] 2.2.1 Support Structure (Different Parts) Fiber support structure: A helical ring structure 102 is employed, composed of electrospun L-polylactic acid (PLLA) fibers. The fibers are circumferentially cross-oriented, with an average diameter of 1-3 μm. The helical ring structure 102 is a continuous structure extending along the axial direction of the support. The width of each helical ring 102 along the axial direction of the support is 2 mm, the pitch (axial distance between adjacent helical rings) is 1.5 mm, and there are approximately 11 turns in total. The radial thickness of the helical ring structure 102 is 100 μm, the fiber porosity is 50%, and the average pore size is 20 μm.

[0071] 2.2.2 Preparation methods (different parts) Step S20: Independently prepare fiber support structure Polylactic acid (PLLA) was dissolved in a mixture of dichloromethane and dimethylformamide (DCM:DMF = 8:2, volume ratio) to prepare a spinning solution with a mass-volume concentration of 13%. Using the same spinning injector 70, voltage, distance, and feed speed as in step S10 of Example 1, the receiver 80 was rotated at 800 rpm (circumferential orientation), while the needle reciprocated along the axial direction of the receiver 80 at a speed of 1 mm / s. Continuous spinning was performed on the receiver 80 with a diameter of 4.2 mm to form a helical tubular fiber for 3 minutes. The helical tubular fiber was removed from the receiver 80 and then cut into segments according to the required number of helical turns to obtain a continuous helical ring body 102. The helical ring body 102 was placed in a vacuum oven and heated to 100°C at a rate of 3°C / min under nitrogen protection, held at that temperature for 2 hours, and then allowed to cool naturally to complete individual annealing.

[0072] Step S30: Install the fiber support structure The annealed spiral ring 102 is coaxially sleeved on the outer surface of the inner fiber layer 101, and its position is adjusted so that it is evenly distributed along the axial direction.

[0073] The other steps (S10, S40) are the same as in Example 1, resulting in the final multilayer vascular tissue engineered fiber scaffold 10. Example 2.3:

[0074] The difference between this embodiment and Embodiment 1 is that the fiber support structure adopts structure (c), namely, multiple ring-shaped bodies 102 and multiple sets of connecting rods 104, with adjacent sets of connecting rods 104 being staggered in the circumferential direction. Everything else is the same as in Embodiment 1.

[0075] 2.3.1 Support Structure (Different Parts) Fiber support structure: includes multiple ring-shaped bodies 102 and multiple sets of connecting rods 104. The ring-shaped bodies 102 are composed of electrospun L-polylactic acid (PLLA) fibers, with the fibers arranged in a circumferential cross-orientation and an average fiber diameter of 0.5μm-3μm. Each ring-shaped body 102 has an axial width of 2mm, and the axial spacing between adjacent ring-shaped bodies 102 is 1.5mm, totaling 11 ring-shaped bodies 102. The radial thickness is 100μm, the porosity is 30%, and the average pore diameter is 20μm. The connecting rods 104 are straight rods, with 4 connecting rods 104 in each group, circumferentially distributed at equal angles (0°, 90°, 180°, 270°). The first group of connecting rods 104 is located between ring 1 and ring 2; the second group of connecting rods 104 is located between ring 2 and ring 3, with a circumferential offset of 45° (45°, 135°, 225°, 315°); the third group is aligned with the first group, and so on. The connecting rod 104 is made of polylactic acid (PLLA) and is 1.5 mm long.

[0076] 2.3.2 Preparation methods (different parts) Step S20: Independently prepare fiber support structure Polylactic acid (PLLA) was dissolved in a mixed solvent of dichloromethane and dimethylformamide (DCM:DMF = 8:2, volume ratio) to prepare a spinning solution with a mass-volume concentration of 13%. The solution was prepared using a stepwise electrospinning method combined with a template method. First, using the same spinning injector 70, voltage, distance, and feed speed as in step S10 of Example 1, and with the receiver 80 rotating at 800 rpm (circumferential orientation), a tubular fiber layer is spun on the receiver 80 with a diameter of 4.2 mm for 5 minutes. Then, a laser cutter is used to cut the outline of the annular body 102 on the tubular fiber layer according to the designed dimensions (width 2 mm, spacing 1.5 mm), but without completely cutting it off.

[0077] Next, the receiver 80 is placed on a programmable rotary table, and connecting rods 104 are formed by spinning at predetermined circumferential positions (first group: 0°, 90°, 180°, 270°) between adjacent annular bodies 102 using a local deposition method. Each connecting rod 104 is spun for 2 minutes.

[0078] Then, the receiver 80 is rotated (45°) and the connecting rod 104 is spun at the second set of positions (45°, 135°, 225°, 315°).

[0079] Repeat the above process to complete the integrated molding of all annular bodies 102 and connecting rods 104.

[0080] The integrated support structure was removed from the receiver 80 and placed in a vacuum oven. Under nitrogen protection, the temperature was increased to 100°C at 3°C / min, held for 2 hours, and then allowed to cool naturally to complete the individual annealing.

[0081] Step S30: Install the fiber support structure The annealed integrated support structure is coaxially sleeved on the outer surface of the inner fiber layer 101, and the position is adjusted to make the annular bodies 102 evenly distributed.

[0082] The other steps (S10, S40) are the same as in Example 1, resulting in the final multilayer vascular tissue engineered fiber scaffold 10. Example 3:

[0083] This application provides a multilayer vascular tissue engineered fiber scaffold system, comprising: The system includes a fiber scaffold 10 of Example 1 or the fiber scaffold 10 prepared in Example 2; and a delivery device loaded with one or more of the fiber scaffolds 10. The delivery device is used to percutaneously deliver the stent to a target vessel 40 in vivo and to complete its expansion and release. Common delivery devices include a balloon catheter 20 or a pusher catheter. Pre-gripping or fitting the stent to the distal end of the delivery device ensures that the stent maintains a small profile both externally and during delivery, facilitating passage through narrow vessels 40 or tortuous paths. Upon reaching the target site, the stent is expanded and adhered to the inner wall of the vessel 40 by balloon 30 expansion or a self-expansion mechanism. This system integrates the fiber scaffold 10, which has excellent tortuosity and a gradient porosity structure, with an interventional delivery device, making it easy for clinicians to use directly and improving the convenience and safety of surgical procedures.

[0084] In some embodiments, the delivery device is a balloon catheter 20. It is understood that the distal end of the balloon catheter 20 is provided with an inflatable balloon 30, and the fiber stent 10 is loaded in a gripped state on the outer surface of the balloon 30. During delivery, the balloon catheter 20 is pushed along the guidewire 50 to the lesion site of the target vessel 40. The balloon 30 is inflated by injecting a pressure medium, thereby radially expanding the stent to a predetermined diameter. After the balloon 30 is fully inflated, the pressure is released to allow the balloon 30 to retract, and the catheter can be withdrawn from the body, leaving the stent in the vessel 40. This delivery method has advantages such as accurate positioning, controllable expansion, and mature operation, and is suitable for stent types requiring active dilation. Example 4:

[0085] This application provides a method for preparing a multilayer vascular tissue engineered fiber scaffold system, comprising the following steps: Step A10: Provide a fiber scaffold 10 and a balloon catheter 20. The fiber scaffold 10 has a hollow tubular structure and includes an inner fiber layer 101, a fiber support structure, and an outer fiber layer 103.

[0086] Step A20: Coaxially sleeve the fiber stent 10 onto the outer surface of the balloon 30 of the balloon catheter 20, so that the stent covers the working section of the balloon 30.

[0087] Step A30: Use a pressure gripping device to uniformly and radially compress the fiber scaffold 10 so that it fits tightly against the surface of the balloon 30, forming a scaffold-balloon assembly in a pressure gripping state.

[0088] Step A40: Disinfect, sterilize, and package the pressed components for later use.

[0089] Understandably, the core of the loading process lies in pre-fixing the stent to the delivery device. This method uses a balloon catheter 20 as the delivery device, and through coaxial fitting and radial compression, the stent is tightly fitted to the surface of the balloon 30, forming a stable stent-balloon assembly. During compression, uniform radial pressure must be controlled to avoid irreversible deformation or localized rupture of the stent's fiber layer. After compression, the assembly is sterilized, disinfected, and packaged for direct clinical use. This method pre-assembles the stent and delivery device, avoiding the uncertainties and contamination risks of temporary loading before clinical use, and ensuring the stent's positional stability during delivery and accuracy during release.

[0090] The working process of the multilayer vascular tissue engineered fiber scaffold in this application is as follows: Step S100: Insert guidewire 50 into the body using vascular puncture technique 40, as follows... Figure 14 As shown in (a), the distal end of the guidewire 50 is passed through the lesion site of the blood vessel 40.

[0091] Step S200: Depending on the condition of the lesion, the lesion site is selectively pre-dilated using balloon catheter 20.

[0092] Step S300: Insert the vascular sheath 60 near the lesion site to establish an interventional device channel, such as... Figure 14 As shown in (b).

[0093] Step S400: The fiber stent 10, pre-compressed and loaded onto the balloon catheter 20 and balloon 30, is advanced along the guidewire 50 to the lesion site in the blood vessel 40, as shown. Figure 14 As shown in (c).

[0094] Step S500: Inflate balloon 30 with a medium to expand it and cause the fibrous stent 10 to expand radially until the stent reaches the target diameter matching the target vessel 40. Maintain the balloon 30 inflated for 1–15 minutes. Figure 14 As shown in (d).

[0095] Step S60: Unload the balloon 30 from its inflated state, allowing the balloon 30 to retract, and then sequentially withdraw the balloon catheter 20, vascular sheath 60, and guidewire 50 from the body.

[0096] Step S70: The fiber scaffold 10 is placed at the lesion site, such as... Figure 14 As shown in (e), its fibrous support structure provides radial support, maintains luminal patency and prevents elastic recoil of the blood vessel 40; the inner fibrous layer 101 induces endothelial cell migration, and the outer fibrous layer 103 guides the migration of blood vessel wall cells, promoting tissue remodeling of the blood vessel 40.

[0097] II. Comparative Example: Comparative Example 1: 1.1 Support Structure This comparative example provides a double-layer fiber scaffold, which has a hollow tubular structure (with an inner tube and an outer tube coaxially sleeved with the inner tube), a total length of 37 mm, and a nominal diameter of 3 mm.

[0098] The first fiber layer (inner tube) located in the inner layer is made of polylactic acid (PLLA) by electrospinning. The fibers are circumferentially cross-oriented and have an average diameter of 1μm-3μm. The thickness of the first fiber layer is 80μm, the porosity is 30%, and the average pore size is 20μm.

[0099] The second fiber layer (outer tube) located on the outer layer is coaxially sleeved outside the first fiber layer. It is made of a mixture of polylactic acid (PLLA) and gelatin (mass ratio 8:2) through electrospinning. The fibers are circumferentially cross-oriented, and the average fiber diameter is 2μm-5μm. The outer fiber layer 103 has a thickness of 70μm, a porosity of 30%, and an average pore size of 30μm.

[0100] 1.2 Preparation Method Step S10: Prepare the first fiber layer Polylactic acid (PLLA) was dissolved in a mixed solvent of dichloromethane and dimethylformamide (DCM:DMF = 7:3, volume ratio) to prepare a spinning solution with a mass-volume concentration of 13%. The spinning injector 70 used an 18G stainless steel needle, applying a +25kV voltage, while the receiver 80 was applied with a -15kV voltage. The distance between the needle and receiver 80 was 15cm, and the spinning solution was propelled at a speed of 4.25mL / h. The receiver 80 was a 4mm diameter stainless steel receiver, and the spinning speed was 10000rpm. The ambient temperature was 30℃, and the humidity was 50%. The spinning time was 3 minutes, forming the first inner fiber layer on the receiver 80.

[0101] Step S20: Prepare the second fiber layer A mixture of polylactic acid (PLLA) and gelatin (mass ratio 8:2) was dissolved in hexafluoroisopropanol (HFIP) to prepare a spinning solution with a mass-volume concentration of 13%. Using the same electrospinning parameters as in step S10, spinning continued for 10 minutes on the outer surface of the first fiber layer (inner tube) to form the second fiber layer (outer tube). The spun support was then removed from the receiver 80 to obtain the final support.

[0102] III. Experimental Examples: 1. Axial bending compliance test The fiber scaffold 10 in Example 2.1 and the scaffold in Comparative Example 1 were subjected to axial bending compliance tests.

[0103] 1.1 Experimental Methods: Place the two supports between the two glass slides, ensuring that both supports are stably clamped between the two slides. The two supports should be placed in the same way to ensure that the glass slides are stable and will not affect the subsequent bending operation.

[0104] Slowly push the upper glass slide to cause the stent to bend, simulating the natural 40° bend of the blood vessel, and observe the bending of the two stents and whether there is fiber breakage or stent bending.

[0105] 1.2 Experimental Results: like Figure 15 As shown: Figure 15 In the example A, the fiber scaffold 10 prepared in Example 2.1 of this application has a large maximum bending angle, and the axial spacing between adjacent annular bodies 102 can be adaptively changed when bending. The stress distribution is uniform, there is no stress concentration, no fiber breakage or bending, and good flexibility. Figure 15 In Comparative Example 1, stent B has a small maximum bending angle, significant stress concentration during bending, and is prone to fiber bending, making it unable to adapt to the natural 40° curvature of the blood vessel.

[0106] The above results show that the axial bending flexibility of the fiber stent 10 in this application is better than that of the stent in Comparative Example 1. The axial spacing design between its annular bodies 102 can effectively release bending stress and avoid stress concentration, thus solving the defects of existing stents that are easy to bend and cannot adapt to the natural curvature of blood vessels 40.

[0107] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0108] Furthermore, it should be noted that the scope of the methods and apparatus in the embodiments of this application is not limited to performing functions in the order shown or discussed, but may also include performing functions substantially simultaneously or in the reverse order, depending on the functions involved. For example, the described methods may be performed in a different order than described, and various steps may be added, omitted, or combined. In addition, features described with reference to certain examples may be combined in other examples.

[0109] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application.

Claims

1. A multilayer vascular tissue engineered fiber scaffold, characterized in that, The support has a hollow tubular structure and includes: Inner fiber layer; A fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer. The fiber support structure includes annular bodies distributed along the axial direction of the support, and there is an axial spacing between adjacent annular bodies. An outer fiber layer, which covers the outer surface of the inner fiber layer and the fiber support structure; Wherein, the fiber porosity of the inner fiber layer is less than or equal to the fiber porosity of the outer fiber layer; The fiber support structure is made of electrospun fibers and is used to provide radial support force.

2. The multilayer vascular tissue engineered fiber scaffold according to claim 1, characterized in that, The fiber support structure adopts any one of the following: (a) Includes multiple independent annular bodies spaced apart along the axial direction of the support; (b) Includes a helical annulus, wherein the helical annulus is a continuous structure or a discontinuous structure with breaks; (c) Includes multiple annular bodies and multiple sets of connecting rods arranged at intervals along the axial direction of the support, with each set of connecting rods disposed between two adjacent annular bodies, and the two sets of connecting rods adjacent along the axial direction being staggered in the circumferential direction.

3. The multilayer vascular tissue engineered fiber scaffold according to claim 2, characterized in that, When the fiber support structure is (c), each group of connecting rods contains 1-8 connecting rods, which are selected from straight rods, corrugated rods or diagonal rods.

4. The multilayer vascular tissue engineered fiber scaffold according to claim 1, characterized in that, When the fiber support structure is (a) or (c), the width of the annulus along the axial direction of the support is 0.5-10 mm, and the axial spacing between adjacent annulus is 0.2-8 mm. When the fiber support structure is (b), the width of the spiral ring along the axial direction of the support is 0.5-10mm, and the axial distance between adjacent spiral rings is 0.2-8mm, which is the pitch.

5. The multilayer vascular tissue engineered fiber scaffold according to claim 2, characterized in that, The inner fiber layer is composed of circumferentially cross-oriented fibers; And / or, the outer fiber layer is composed of fibers with a circumferential cross-orientation; And / or, the fibers of the fiber support structure have a circumferential cross-orientation structure or a random orientation structure; And / or, the porosity of the inner fiber layer is 30%-95%, the porosity of the outer fiber layer is 40%-95%, the porosity of the fiber support structure is 20%-80%, and the fiber porosity of the fiber support structure is less than or equal to the fiber porosity of the inner fiber layer.

6. The multilayer vascular tissue engineered fiber scaffold according to claim 1, characterized in that, The average pore size of the inner fiber layer is 0.5-100 μm, the average pore size of the outer fiber layer is 0.5-200 μm, and the average pore size of the fiber support structure is 0.5-100 μm. Furthermore, the average pore size of the fiber support structure is less than or equal to the average pore size of the inner fiber layer, and the average pore size of the inner fiber layer is less than or equal to the average pore size of the outer fiber layer.

7. A method for preparing a multilayer vascular tissue engineered fiber scaffold according to any one of claims 1-6, characterized in that, Includes the following steps: Electrospinning is used to form an inner fiber layer on the receiver; The fiber support structure is independently prepared by electrospinning, and the fiber support structure includes a ring-shaped body. The fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer; Electrospinning is used to form an outer fiber layer on the outer surface of the inner fiber layer and the fiber support structure, and the fiber support structure is wrapped between the inner fiber layer and the outer fiber layer.

8. The method for preparing a multilayer vascular tissue engineered fiber scaffold according to claim 7, characterized in that, The method also includes a step of annealing the fiber support structure at a temperature higher than the glass transition temperature of the material constituting the annulus and lower than the melting temperature of the material constituting the annulus; the annealing heat treatment is performed in any one or a combination of two of the following stages: (i) Before the fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer, the fiber support structure is annealed separately; (ii) After the fiber support structure is coaxially sleeved on the outer surface of the inner fiber layer and before the outer fiber layer is formed, the inner fiber layer on which the fiber support structure is sleeved is annealed together. (iii) After the outer fiber layer is formed, the inner fiber layer, the fiber support structure and the outer fiber layer are annealed as a whole.

9. The method for preparing a multilayer vascular tissue engineered fiber scaffold according to claim 7, characterized in that, The steps for independently preparing the fiber support structure include: when the fiber support structure is multiple independent rings, using electrospinning to prepare tubular fibers, and then cutting the tubular fibers into rings; when the fiber support structure is a spiral ring, using electrospinning, while the receiver rotates, the needle moves back and forth along the receiving axis to directly form a spiral ring, and then cutting it into segments according to the required number of spiral turns; And / or, the parameters of the electrospinning include: a voltage applied to the needle of the spinning injector of 0 kV to +50 kV, a voltage applied to the receiver of 0 kV to -30 kV, a distance between the needle of the spinning injector and the receiver of 5 cm to 25 cm, a spinning solution propulsion speed of 0.5 to 8 mL / h, a receiver rotation speed of 50 rpm to 20000 rpm, a spinning ambient temperature of 15°C to 45°C, and a humidity of 30% to 70%. And / or, the mass / volume concentration of the solution used for electrospinning is 6% to 20%; And / or, the solvent used for electrospinning is selected from one or more of dichloromethane, chloroform, acetone, ethyl acetate, dimethylacetamide, dimethyl sulfoxide, and hexafluoroisopropanol.

10. The method for preparing a multilayer vascular tissue engineered fiber scaffold according to claim 7, characterized in that, The inner fiber layer, the outer fiber layer, and the fiber support structure may be made of the same or different materials, and each is selected from one or more of bioabsorbable polymers, non-bioabsorbable materials, and biological components. The bioabsorbable polymer is selected from one or more of polylactic acid, polyglycolic acid, polymalonolactone, polydioxanone, polystyrene carbonate, poly(4-hydroxybutyrate), polyesteramide, polyurethane, polyethylene glycol, polyvinylpyrrolidone and its copolymers, wherein the polylactic acid includes one or more of poly-L-lactic acid, poly-D-lactic acid, and poly-D,L-lactic acid. The non-biological absorbent material is selected from one or more of polypropylene, polyethylene, polyethylene terephthalate, polytetrafluoroethylene, polyaryl ether ketone, polyamide, fluorinated ethylene propylene copolymer, polybutylene, and polysiloxane. The biological components are selected from one or more of hyaluronic acid, collagen, gelatin, alginate, pectin, and cellulose.

11. A multilayer vascular tissue engineered fiber scaffold system, characterized in that, include: The multilayer vascular tissue engineered fiber scaffold according to any one of claims 1-6; as well as A delivery device on which one or more of the multilayer vascular tissue engineered fiber scaffolds are loaded.

12. A method for preparing the multilayer vascular tissue engineered fiber scaffold system as described in claim 11, characterized in that, Includes the following steps: Provide a multilayer vascular tissue engineered fiber scaffold as described in any one of claims 1-6; The multilayer vascular tissue engineered fiber scaffold is press-loaded onto a delivery device to form the multilayer vascular tissue engineered fiber scaffold system.

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