A graft

Abstract

A graft is provided that consists of a bioabsorbable network of polymer fibers that can rearrange upon dilation to provide an enlarged diameter and support a biological conduit. Additionally, a graft is provided in which the rearranged fiber network in the expanded state of the graft can act as a scaffold for cell infiltration and promote autologous tissue formation.

Description

[0001] This application is a divisional application of the invention patent application with the application date of January 9, 2017, the application number of "201780016422.X", and the invention name of "Fiber Tubular Catheter for Stent Application". Technical Field

[0002] The present invention relates to stents and regenerative medicine. In particular, the present invention relates to a fiber tubular catheter that has stent capabilities upon expansion and serves as a minimally invasive deliverable scaffold for cell infiltration and triggers the generation of tissue using the patient's own cells. Background Art

[0003] A stent is generally defined as a tubular network of structural elements (commonly referred to as struts or strut arms), where expansion is described as the movement of the individual structural elements. Methods for creating a strut pattern on a tubular structure include laser cutting, die stamping, chemical etching, etc. Once expanded, the stent struts move away from each other, causing an increase in diameter. Balloon-expandable stents and self-expandable stents rely on the presence of struts to deploy minimally invasively and on the mechanical properties of the substrate to withstand the forces exerted by the implantation tool and the host tissue.

[0004] Technological advancements in the field of regenerative medicine have shown that fiber grafts can induce autologous tissue formation. A tubular fiber structure made of a bioabsorbable polymer can be implanted to act as a temporary scaffold for guiding tissue formation. However, grafts with regenerative capabilities cannot act as stents. Due to their lack of support capabilities, they require surgery or must be combined with an additional support device (such as a stent to be implanted).

[0005] Bioabsorbable polymers with high mechanical properties (such as PLA) have the drawback of exhibiting brittle fracture. Fibers made of brittle polymers exhibit low deformation before they reach their breaking point. However, corrugated fibers made of the same material can first straighten and eventually stretch and deform (first elastically and then plastically). Additionally, the presence of interconnects within these fibers will result in the possibility of overcoming these interconnects during stretching. A tubular construct made of an interconnected fiber network benefits from the described mechanisms to achieve expansion of the construct without compromising its integrity and provides the ability to perform structural functions during expansion.

[0006] The present invention advances the prior art by overcoming at least some of the current drawbacks of support devices that can be deployed by rearrangement of a fiber network without using a strut pattern. Additionally, the present invention advances the prior art by providing the support device with the ability to promote autologous tissue formation (acting as a regenerative stent). Summary of the Invention

[0007] The present invention provides a biocompatible and bioresorbable scaffold. The scaffold is a tubular structure composed of a fiber network, and the fibers can rearrange without relying on a strut pattern to provide diameter expansion at the implantation site. In addition, the tubular structure in its expanded configuration can provide structural support for host tissue, allow minimally invasive anchoring, and, if needed, serve as a framework with regenerative, restorative, growth, and / or repair capabilities, enabling cell infiltration / adhesion / proliferation and new tissue formation.

[0008] The term "fiber network" refers to an arrangement of interconnected fibers, where the fibers are in the form of long filaments and two types of interconnects can be defined. The fibers can be adjacent to each other or on top of each other, defined as non-bonded interconnected fibers. The fibers can merge while being adjacent to each other or on top of each other, defined as physically bonded interconnected fibers.

[0009] Because the fiber tubular network can provide structural support for a biologic conduit after minimally invasive implantation, it can act as a scaffold, but it differs from other scaffolds in that it does not rely on large holes defined by the profile of the scaffold struts to provide diameter expansion, but rather entirely on the rearrangement of its fiber network.

[0010] This scaffold differs from other vascular grafts in that it provides the possibility of minimally invasive implantation without the need for additional medical devices (i.e., supplemental stents), provides structural support for the graft, and / or enables the graft to be anchored within host tissue to prevent movement.

[0011] The present invention is both a scaffold and a tissue engineering framework, defining a fibrous bioresorbable scaffold with regenerative capabilities, or simply defined as a regenerative scaffold.

[0012] Specifically, a scaffold is provided for implantation into a biologic conduit. The scaffold is an expandable tubular structure made of a fiber network. The fiber network identifies a first state via a first diameter of a tubular conduit determined by a first fiber orientation. The first fiber orientation is characterized by a first fiber dispersion value, a first major angle difference, and a first average fiber diameter. The fiber network further identifies a second state via a second diameter of the tubular conduit determined by a second fiber orientation. The second fiber orientation is characterized by a second fiber dispersion value, a second major angle difference, and a second average fiber diameter. The first diameter of the tubular conduit is less than the second diameter of the tubular conduit.

[0013] The transition from the first state to the second state is provided only by rearrangement of the fibers in the fiber network and does not rely on a strut pattern. The rearrangement of the fiber network from the first state to the second state is accomplished by: (i) stretching the fibers in the fiber network, (ii) sliding, breaking, or a combination thereof of the fiber interconnects in the fiber network, and can be facilitated by acting on the wettability of the fiber network, or a combination of (i) and (ii).

[0014] The fiber network in the second state provides mechanical support for the biological conduit. The fiber network in the second state can allow cell infiltration and act as a scaffold to induce autologous tissue formation.

[0015] In one variant, the first fiber orientation is an arrangement of random fibers, and in this arrangement, the first fiber dispersion value is greater than the second fiber dispersion value.

[0016] In another variant, the first fiber orientation is an arrangement of controlled fibers, and in this arrangement, the first major angular difference is equal to or greater than the second major angular difference.

[0017] In yet another variant, the first fiber diameter is equal to or greater than the second fiber diameter.

[0018] In another variant, rearrangement of the fiber network can be facilitated by acting on the wettability of the fiber network to provide a transition from state 1 to state 2.

[0019] In another variant, the tubular construct can consist of one or more layers.

[0020] In another variant, the tubular construct is shaped to induce a change in geometry or opening.

[0021] In another embodiment, the present invention relates to a method for manufacturing a scaffold using bioabsorbable fibers, the method comprising the steps of providing a tubular mold, defining a fiber polymer network on the mold, and separating the material from the mold. The fiber network can, but does not necessarily, be produced by electrospinning.

[0022] In yet another embodiment, the present invention relates to a method for manufacturing a valve scaffold, the method comprising the step of providing a leaflet structure to the scaffold (by suturing the leaflets, or by forming or defining the leaflets by a less dense fiber network that can bend inward).

[0023] In yet another embodiment, the present invention relates to a method for minimally invasive alleviation of obstructive diseases, the method comprising identifying an occluded blood vessel or other tubular conduit in need, and inserting a tubular construct into the blood vessel or conduit. The composition can, but does not necessarily, allow new tissue formation.

[0024] In yet another embodiment, the present invention relates to a method for minimally invasive delivery of a tissue engineering scaffold for blood vessels, the method comprising identifying a blood vessel in need of tissue repair or tissue engineering, and inserting a tubular construct into the blood vessel. New blood channels are designed within the native artery.

[0025] In yet another embodiment, the present invention relates to a method for minimally invasive treatment of patients suffering from cardiovascular diseases, the method comprising identifying a blood vessel in a patient in need of occlusion relief or tissue engineering, and inserting a tubular construct into the blood vessel.

[0026] In yet another embodiment, the present invention relates to a method for minimally invasive treatment of an aneurysm artery, the method comprising identifying a blood vessel having an aneurysm, and inserting a tubular construct into the blood vessel. A new blood channel is designed within the natural artery.

[0027] In yet another embodiment, the present invention relates to a method for minimally invasive treatment of congenital heart diseases in growing patients, the method comprising identifying a blood vessel in said patient, and inserting a tubular construct into the blood vessel. A new blood channel is designed within the natural artery and does not impede somatic growth. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figures 1A to 1C Showing an exemplary embodiment according to the present invention: implanting a construct within an occluded blood vessel ( Figure 1A ), the construct expanding, fiber reorganization occurring and cells from the blood infiltrating into the fiber mesh ( Figure 1B ), wherein the cells synthesize new tissue while the fibers safely dissolve over time after the newly formed blood vessel is retained ( Figure 1C ).

[0029] Figure 2 Showing an exemplary embodiment according to the present invention: defining the respective orientations of the construct relative to the fibers ( Figure 2 ).

[0030] Figures 3A to 3B Showing an example of how to generate a construct using electrospinning according to an exemplary embodiment of the present invention, and how to obtain a random fiber orientation ( Figure 3A ) and how to obtain a controlled fiber orientation ( Figure 3B ).

[0031] Figures 4A to 4B Showing an exemplary embodiment according to the present invention: for an expanded diameter construct changing from state 1 to state 2, how to reorganize the fibers in a random fiber orientation scenario ( Figure 4A ), and for an expanded diameter construct changing from state 1 to state 2, how to reorganize the fibers in a controlled fiber orientation scenario ( Figure 4B ).

[0032] Figures 5A to 5B Showing an exemplary embodiment according to the present invention: after image analysis of images obtained by a microscope, how the main angle and dispersion value of the construct change when entering from state 1 to state 2 in a random fiber orientation scenario. Here, the main parameter of interest is the realignment index Iσ (Figure 5A ) In a controlled fiber orientation scenario, two distinct peaks can be identified after image analysis processing. In this case, the main parameter of interest is the reorientation index I Δα ( Figure 5B ).

[0033] Figure 6 Show the range of the realignment index (Iσ) and the reorientation index (I Δα ) that will apply to the transition from state 1 to state 2 ( Figure 6 ).

[0034] Figures 7A to 7F show an exemplary embodiment according to the present invention: wherein a fibrous structure has been produced and its diameter has been enlarged to transition from state 1 to state 2 (Figure 7A). In this case, the diameter has been enlarged from 1299 μm in state 1 to 4099 μm in state 2 (Figure 7B). When the structure is in states 1 and 2, micrographs of the fibers are made using a scanning electron microscope (Figures 7C to 7D). The images are analyzed using image analysis software (Fiji, ImageJ), which determines that the σ1 value = 26.24° and the σ2 value = 14.00° (Figures 7E to 7F). This results in a realignment index Iσ = 0.53, determining fiber reorganization.

[0035] Figure 8 Show an exemplary embodiment according to the present invention: how, after a PLA-based electrospun scaffold immersed in an ethanol solution to enhance stretchability is transformed into state 2, simultaneous diameter enlargement and load-bearing capacity can be obtained, and the crushing force is evaluated after subsequent ethanol evaporation.

[0036] Figures 9A to 9D Show an exemplary embodiment according to the present invention: how different aqueous alcohol solutions ( Figures 9A to 9D ) in contact with a PLA-based solid surface affect the wettability of the polymer surface. The contact angle of the alcohol droplets on the PLA surface is calculated to determine the wettability. Pure water without alcohol has a contact angle of 85°. By mixing water with 25% methanol, the contact angle drops to 60°, with 25% ethanol, it drops to 45°, and with 25% 1-propanol, it drops to 20°. Here, the method of using longer-chain alcohols is used to increase the stretchability of the PLA structure in a laboratory environment.

[0037] Figure 10Shows an exemplary embodiment according to the present invention: the effect of the regulated wettability of the surface of polymer fibers using different alcohols on the mechanical properties of PLA-based fiber conduits. Compared to pure water, the inclusion of methanol results in a 2.5-fold increase in elongation at break, while ethanol results in a 3.67-fold increase, and 1-propanol even prevents ring rupture. This confirms that increasing the wettability of the surface of polymer fibers comprising a fiber network is understood as an increase in elongation at break.

[0038] Figure 11 Shows an exemplary embodiment according to the present invention: the effect of temporarily regulating the wettability of the surface of fibers comprising a fiber network using an alcohol (such as ethanol) on the mechanical properties of a PLA-based fiber tubular conduit. Tests were conducted on: i) dry electrospun rings, ii) rings immersed in pure water, iii) rings immersed in a 25% ethanol solution, and iii) rings immersed in a 25% ethanol solution after depletion of water by multiple washing steps in water. This shows that ethanol has a temporary effect and then depletes, and the mechanical properties are almost fully restored.

[0039] Figure 12 Shows an exemplary embodiment according to the present invention: the effect of strain rate on the mechanical properties of a PLA-based fiber tubular conduit that occurs in pure water. Reducing the strain rate improves fiber reorganization to enhance the tensile ability of the construct.

[0040] Figure 13 Example A shows the traditional concept of stent expansion based on a strut pattern. Outside the solid wall tube, a strut pattern is embedded to make the structure act as a stent. Expansion from state 1 to state 2 is achieved through geometric adjustment of the strut pattern, where the established open voids become larger. According to an exemplary embodiment of the present invention, Example B shows the concept of using fiber reorganization to allow stent expansion. Expansion from state 1 to state 2 is achieved only through reorganization of the fibers in the fiber network and thus does not rely on the strut pattern. The structural support in state 2 is shown by the maintained diameter expansion achieved in a silicon simulated blood vessel.

[0041] Figures 14A to 14F In Figure 14A is shown an exemplary embodiment according to the present invention, where a device inserted by a minimally invasive approach is fixed to a balloon catheter. Figure 14B Shows a device that undergoes a transition from state 1 to state 2 during stent deployment, thereby anchoring the device to an artery. Figure 14C Shows that after removal of the balloon catheter, the device maintains mechanical support to keep the stenotic area open. Figure 14D Shows an enlarged view of the wall of the construct to show that the porous structure is entirely composed of stacked fiber layers that make up the fiber network. Figure 14EShows the ability of host cells to infiltrate a porous mesh. In this example, cells from the bloodstream attach to the fibers on the inner side of the lumen and also to the fibers on the lumen side. Figure 14F Shows that the fiber network is absorbed by the body as cells synthesize new tissue that fills the internal voids of the fiber mesh.

[0042] Figure 15 Shows a sliding non-bonded interconnect (i) according to an exemplary embodiment of the present invention, which is initially located at reference point 1 and repositioned when the construct expands.

[0043] Figure 16 Shows according to an exemplary embodiment of the present invention: complete fracture of the interconnect (i) of physically bonded fibers, leaving individual fibers 1 and fiber 2 intact.

[0044] Figure 17 Shows according to an exemplary embodiment of the present invention: partial fracture of the interconnect (i) of physically bonded fiber 1 and physically bonded fiber 2, breaking one of the fibers (i.e., fiber 1).

[0045] Figures 18A to 18C Shows a regenerative stent implanted in the abdominal aorta of a rat according to an exemplary embodiment of the present invention. Figure 18A Provides in vivo evidence of minimally invasive implantation of a regenerative stent in an animal model. Figure 18A Also shows that the stent provides structural support to the artery after implantation by showing an open and patent artery. Figure 18B Shows the histology of an explant of an embodiment two weeks after implantation in the abdominal aorta of a rat. Cells are present on the native artery and the stent. Uniform infiltration of host-derived cells is marked by prominent dots representing individual cells. In Figure 18C Shows a histological picture of a portion of the stent in the abdominal aorta of a rat. The native artery is shown in the upper right, where the embodiment is located in the lower left. Two weeks after implantation, signs of new tissue formation throughout the stent are confirmed by the presence of darkly stained tissue components.

[0046] Figure 19 Shows different types of clinically relevant vascular applications in which a regenerative stent can be used according to an exemplary embodiment of the present invention.

[0047] Figures 20A to 20E Shows a method of manufacturing a valve stent according to an exemplary embodiment of the present invention. The valve stent has a fibrous polymer tubular conduit (1) (thickness T1 and length L1) serving as the stent ( Figure 20A ) and a fibrous polymer tube (2) (thickness T2 and length L1) serving as the valve skeleton ( Figure 20B ). The valve skeleton can be placed inside or outside the stent ( Figure 20C ). The valve skeleton is turned inside out to create a valve within the stent ( Figure 20D)。A constraint member (such as a bioabsorbable suture) or an insert can be placed on the scaffold to define the leaflets of the valve. Figure 20E )。In this case, a three-leaflet valve scaffold is produced.

[0048] Figures 21A to 21D Showing an exemplary embodiment according to the present invention: After implantation, the fibrous catheter can be located in front of a bifurcation or other opening. Detailed Embodiments

[0049] The term "tubular" pertains to an approximate shape of a cylinder and can include conical shapes or other variants, such as curved, side-branched, bifurcated, sinusoidal, elliptical, concave, and convex sections.

[0050] The term "biological conduit" refers to a part of the circulatory system (including the cardiovascular system associated with arteries, veins, and capillaries (pulmonary and systemic circulation, i.e., the vasculature associated with the heart, such as coronary vessels and the peripheral vascular system), the neurovascular system, and the lymphatic system), a part of the digestive system (including the gastrointestinal tract), a part of the urinary system, or any associated organ thereof, or any other part of a biological system in which a conduit can be defined and the conduit is adapted to receive a scaffold according to an embodiment of the present invention.

[0051] The term "structural support" refers to the ability to open a biological conduit that, after springing back, results in an increased diameter or maintains the original diameter of the biological conduit, preventing collapse and / or maintaining patency. One way to evaluate the structural support ability is to determine the force after vertical or radial compression.

[0052] The term "scaffold" refers to a structure capable of infiltrating, attaching, and / or growing cells and / or tissues.

[0053] The term "stent" refers to a structure that provides structural support to a biological conduit during self-expansion or balloon expansion.

[0054] The term "construct" refers to a tubular shape that can act as a scaffold or a stent. For example, a scaffold can be defined as a construct that does not necessarily provide structural support.

[0055] The term "regenerative stent" refers to a tubular fibrous construct that serves both as a scaffold and a stent.

[0056] The present invention describes a tubular construct composed of a bioabsorbable fiber network having interconnected fiber layers. The construct can be minimally invasively delivered into a biological conduit. Once at the intervention location Figure 1A ), the construct will undergo a transition from state 1 Figure 14A ) to state 2 Figure 14B ), inducing the fibers to enhance their rearrangement towards the circumferential direction during expansion.Figure 2 ), expanding the diameter of the construct. The construct can provide structural support to the biological conduit in state 2 and serves as a scaffold that does not rely on a strut pattern to achieve expansion ( Figure 14C ). Due to the fibrous nature of the pores, pores are defined in the structure ( Figure 14D ) and cells from blood and adjacent tissues can infiltrate into the construct ( Figure 1B and Figure 14E ). The infiltrated cells can synthesize new tissue ( Figure 14F ). Over time, the fibrous network can safely dissolve in the body. This will ultimately result in the reconstructed tissue ( Figure 1C ). An additional benefit for cardiovascular applications is that due to the consistent porous structure, a gradual and uniform degradation of the construct can be expected, and endothelialization will be alleviated, reducing the risk of inflammation and thrombosis. In addition, due to the absence of a strut pattern in the stent profile, severe turbulence is expected to be prevented.

[0057] By combining the advantages of a fully biodegradable scaffold composed of a fibrous network and the advantages of a regenerative scaffold, the device can allow for: minimally invasive delivery, large expansion ratios, structural support during inflation, temporary support, enhanced resorption, prevention of internal leakage, complete lesion coverage, cell infiltration, native tissue formation, prevention of construct shrinkage, uniform endothelialization, prevention of turbulence, low-profile constructs, enhanced flexibility, regression of disease, restoration of the biological conduit function and natural growth of the biological conduit, or combinations thereof.

[0058] In some embodiments, the diameter expansion will promote the circumferential alignment of the fibers. This will enhance the load-bearing capacity of the scaffold and be beneficial for native-like tissue formation. Cells can align along the fibers of the construct and produce tissue components (such as collagen) similar to native structures in the same direction.

[0059] In some embodiments, the rearrangement of the fibrous network can result in fiber stretching. Thus, the fibers can elongate without causing brittle behavior that leads to construct failure during expansion. By aligning the polymer chains, fiber stretching can be beneficial for the local mechanical fiber properties at the molecular level, which results in a strengthening effect of the fibers.

[0060] Manufacturing method

[0061] In an exemplary embodiment, the fibrous tubular conduit can be produced by using electrospinning technology. A biodegradable polymer can be dissolved in a solvent to obtain a polymer solution. The solution can contain a single polymer or multiple polymers that form a blend. The polymer solution is directed to the nozzle of an electrospinning device. A mandrel is rotated to be located in front of the nozzle at a predetermined distance. A voltage difference is applied between the nozzle and the mandrel, thereby forming a Taylor cone in front of the nozzle. From this Taylor cone, a continuous polymer jet is ejected towards the mandrel. Due to the rotation of the mandrel, the polymer fibers are wound around the target. By moving the nozzle back and forth along the length of the target, the length of the electrospun scaffold can be defined ( Figure 3A ).

[0062] To control the orientation of the fibers on the target from a random structure to an aligned structure, the electrospinning settings can be adjusted. There are various possible combinations of parameters to achieve this state. One example is to increase the rotational speed of the mandrel, whereby the fibers will be more circumferentially aligned on the target ( Figure 3B ). To control the angle of the fibers relative to the symmetry axis of the target, the moving speed of the nozzle can be adjusted while spinning the aligned fibers. By defining the rotational speed of the mandrel, the appropriate moving speed of the nozzle can be calculated to achieve a controlled fiber angle. The moving speeds in the forward and backward directions can be set separately to produce one or more main fiber angles. When preferred, multiple nozzles can spin on the same target under different conditions to simultaneously use multiple polymer materials. By changing the respective conditions from multiple nozzles, random fibers and aligned fibers can also be spun onto a target simultaneously. By setting the spinning time, the wall thickness of the scaffold can be controlled. The electrospinning settings, the composition of the solvent, and the concentration of the polymer solution can be adjusted to control the fiber diameter and pore size.

[0063] Other production methods for producing similar fibrous constructs can be: emulsion electrospinning, coaxial electrospinning, melt electrospinning, electrostatic stretching, weaving, knitting, knitting, additive manufacturing, 3D printing, bioprinting, electrospraying, polymer jetting, injection molding, casting, or any other fiber production method, or a combination thereof.

[0064] After manufacturing, the fiber network will require an annealing step. Annealing is a heat treatment that can change the physical and / or chemical properties of the material. In some cases, the fiber network will be heated above Tg. The annealing temperature will be maintained for a specified period of time, followed by a cooling phase. Annealing can be carried out in several steps, and each step can have various repetitions and durations between cycles and repeats.

[0065] The optimal material for manufacturing the construct depends on the nature of the biological conduit into which it will be inserted and the disease to be treated. Biocompatible materials can include:

[0066] · Biodegradable polymers (such as polylactic acid (PLA), including poly(L-lactide), poly(D-lactide), poly(D,L-lactide), and polyglycolic acid (PGA), polycaprolactone, polydioxanone, poly(trimethylene carbonate), poly(4-hydroxybutyrate), poly(ester amide) (PEA), polyurethane, poly(trimethylene carbonate), poly(ethylene glycol), poly(vinyl alcohol), polyvinylpyrrolidone, and their copolymers),

[0067] · Non-biodegradable materials (such as polypropylene, polyethylene, polyethylene terephthalate, polytetrafluoroethylene, polyaryletherketone, nylon, fluorinated ethylene propylene, polybutester, silicone, or their copolymers),

[0068] · Biological components (such as hyaluronic acid, collagen, gelatin, chitosan, alginate, aloe / pectin, cellulose, or other biological materials derived from autologous, allogeneic, or xenogeneic sources of tissue),

[0069] · Or a combination thereof.

[0070] The polymer can be of the D-isotype, L-isotype, or a mixture of both. Multiple polymers and copolymers can be mixed and co-blended in different ratios. The polymer fibers can be cross-linked. Some embodiments can include supramolecular chemistry (including supramolecular polymers), linking mechanisms or groups. Some embodiments can include shape memory polymers.

[0071] In some embodiments, multiple fiber layers with different densities can be combined. By adjusting the porosity of the fiber layers, cell infiltration can be prevented or achieved, thereby preventing or achieving tissue formation. Adjusting the fiber spacing and / or fiber diameter and layer thickness can change the conditions of cell infiltration. In this way, cell infiltration and migration can be controlled with a dense structured layer facing the outer side and / or lumen side of the construct.

[0072] An impermeable layer can be added based on densely packed fibers (which are porous structures with high surface tension) or a non-porous network to prevent fluid leakage; for purposes such as closing a lesion or a duct that needs to be closed.

[0073] In some embodiments, the rate of bioresorption can be adjusted by acting on the molecular weight of the polymer, giving the polymer different inherent bioresorption rates, and / or changing the porosity of the fiber network, fiber diameter, and / or the number of stacked fiber layers.

[0074] Methods of testing / evaluating

[0075] To evaluate the fiber distribution and orientation of fibers from a fiber network, microscopic images can be obtained, for example, by using a scanning electron microscope. After obtaining the macroscopic image, image analysis software can be used to calculate the obtained fiber distribution and orientation. An example of free image analysis software is Fiji (ImageJ). By using a directionality plugin, analyzing the image by using Fourier components or by calculating the local gradient direction, the fiber orientation and distribution are calculated. The software will fit a mathematical distribution to the data, which is a Gaussian distribution in the standard configuration. In this way, a fiber dispersion value (σ) and a major fiber angle (α) can be obtained, where the fiber angle is the center and the dispersion value is the standard deviation of the Gaussian fit.

[0076] To enable minimally invasive implantation and anchoring of the construct, once it is positioned at the desired location within the biological conduit, an increase in diameter is required. By utilizing the fiber reorganization of the fiber network constituting the construct, the diameter expansion of the construct is promoted.

[0077] To distinguish between the initial state and the expanded state, we define state 1 as the construct after production and state 2 as the same construct after diameter expansion. When state 2 is reached, the construct can act as a scaffold. To be able to expand the diameter, fiber reorganization between state 1 and state 2 must be induced. The fiber network of the construct in state 1 can have a random fiber organization (scenario A) or a controlled fiber organization (scenario B), or a combination thereof.

[0078] Scenario A: Random fiber orientation

[0079] State 1: Defined as a framework with randomly oriented fibers ( Figure 4A ). The directionality histogram describes a wide peak region with several maximum high intensities, which defines a rather flat Gaussian fit curve ( Figure 5A ). This is captured by a relatively high fiber dispersion value σ. In this case, the fiber angle α only describes the center of the Gaussian curve and has no real physical relevance.

[0080] State 2: The diameter of the framework from state 1 has expanded to form state 2, which results in realignment of the fibers ( Figure 4A ). The directionality histogram describes a narrowing peak area around a preferred orientation ( Figure 5A ). This is captured by a reduced σ value and an α value close to 90 degrees, which is defined here as the circumferential direction ( Figure 2 ).

[0081] The relevant parameter here is σ. To demonstrate fiber alignment, the degree of fiber dispersion is quantified by comparing σ in state 1 (σ1) and σ in state 2 (σ2), resulting in a realignment index, which is defined as Iσ = σ2 divided by σ1 and can describe any range between no alignment (Iσ = 1) or full alignment (Iσ = 0). Any Iσ < 1 confirms the induction of fiber reorganization to enable the transition from state 1 to state 2 ( Figure 6 ).

[0082] For clarity, even a small degree of realignment is crucial as it enables diameter enlargement without the need for strut patterns, which is different from traditional stents that typically rely on large pores for dilation. Here, lower realignment index values are expected to have favorable mechanical properties.

[0083] Scenario B: Controlled fiber orientation

[0084] State 1: Defined as a scaffold with fibers distributed in one or more major directions. The directional histogram in this instance describes two major orientations through two narrow peaks that define the major angles α1 and α2. The fiber dispersion values σ1 and σ2 are low (consistent with a high degree of fiber alignment in two directions).

[0085] State 2: The diameter of the scaffold from state 1 has been enlarged to obtain state 2, which results in the reorientation of the fibers. The directional histogram describes two narrow peaks that have become closer to 90 degrees, describing circumferential alignment. Clearly, the relevant parameter here is α. However, the major angle difference (Δα) describes the presence of two fiber families, and the decrease in Δα between states describes alignment. The reorientation index is defined as I Δα = Δα2 divided by Δα1 and can describe any range between no reorientation (I Δα = 1) or full reorientation (I Δα = 0). Any I Δα < 1 confirms the induction of fiber reorientation to enable the transition from state 1 to state 2 ( Figure 6 ).

[0086] The construct can be balloon-expandable. Here, a tubular construct can be produced to meet state 1. The construct is mounted on the balloon of a balloon catheter. The construct can be annealed on the balloon to promote proper fixation of the construct. At the time of implantation, the balloon will expand and the construct will deploy into the biological conduit. When the balloon is deflated, the construct will reach state 2.

[0087] The construct can be self-expanding. Here, a larger diameter construct can be produced and crimped to reach state 1. The stent is loaded into an isolating catheter device. Once implanted, the isolator will be removed and the stent will deploy into the biological conduit to reach state 2.

[0088] In one embodiment of the present invention, the fibers will be exposed to circumferential strain upon expansion. The fibers will be stretched circumferentially and will overcome the interconnections, causing the diameter of the structure to increase without exhibiting brittle behavior. In this way, the fiber network rearranges such that the diameter increases. In state 2, the expanded construct will support the load of the already implanted biocathode to serve as a stent, which will be achieved by appropriately selecting materials and mechanical properties that prevent the structure from collapsing.

[0089] Comparison

[0090] The fibers in existing stents in the art do not / will not reorient and / or realign, stretch and / or straighten when the stent diameter increases. Due to rotation by opening the strut pattern, these fibers may change orientation. However, in the case where these fibers are randomly oriented in state 1, they will remain random in state 2. This results in Iσ = 1. Additionally, in the case where these fibers are controllably oriented (aligned circumferentially) in state 1, they will become less circumferentially aligned in state 2. In that case, I Δα > 1.

[0091] Overcoming the interconnections

[0092] As described above, the fiber tubular catheter can be minimally invasively implanted to support the biocathode. Once expanded, fiber reorganization is necessary to achieve diameter expansion without compromising the integrity of the construct, and then the reoriented fibers need to ensure proper anchoring of the construct and patency of the biocathode. For this purpose, not only the mechanical behavior of individual fibers but also the interaction between fibers needs to be considered.

[0093] Fibers joined together by fiber interconnections can form a tubular construct. The fibers can be adjacent to each other or on top of each other, defined as non-bonded interconnected fibers. The fibers can merge while being adjacent to each other or on top of each other, defined as physically bonded interconnected fibers. To facilitate fiber rearrangement during diameter expansion, the fiber interconnections can be overcome. Overcoming the fiber interconnections during diameter expansion can enhance the mobility of the fibers, allowing them to straighten, reorient, elongate, and / or slide; improving the stretchability of the tubular construct.

[0094] The term "overcoming the interconnections" in this application means:

[0095] a) Sliding non-bonded fibers, the interconnections will relocate. As Figure 15 shown, two fibers are initially interconnected at point (1), where the interconnection is represented by the circle (i). Initially, (1) and (i) coincide. When a tensile force is applied to the fiber network, the interconnection (i) slides to a different position, different from the position of point (1).

[0096] b) Disconnect the interconnection of the bonding fibers, where the bonded interconnection can be regarded as a predetermined breaking point. In this case, strain will accumulate at the interconnection, which will ultimately:

[0097] b1) Complete destruction: Keep the two fibers intact. As Figure 16 shown, the two fibers (1) and (2) are bonded at the interconnection (i). When tension is applied to the fiber network, the interconnection disappears and the fibers become independent;

[0098] b2) Partial destruction: Divide one of the fibers. As Figure 17 shown, the two fibers (1) and (2) are bonded at the interconnection (i). When tension is applied to the fiber network, the interconnection is destroyed and the fiber (1) is divided into two segments.

[0099] Repositioning the interconnection may be necessary for the mechanical integrity of the expanding fiber graft.

[0100] Wettability

[0101] Wettability is an important factor that can affect the rearrangement ability of the fiber network in an aqueous environment. Adjusting the wettability of the fiber network can affect the mechanical properties and biological interactions of the fibers, as well as the degradation rate and interconnection, thereby making it easier for the fiber network to rearrange. The wettability of the fiber structure must be adjusted in such a way that it allows the rearrangement of the fibers present in the fiber network when the diameter expands, and also requires the rearranged fiber network to maintain the mechanical load applied by the biological conduit.

[0102] At the fiber level, adjusting the wettability can affect (but is not limited to);

[0103] · The ability of water to penetrate into the polymer, and thus can affect:

[0104] o The Tg and Tm of the polymer (copolymer), and the mechanical properties can thereby be changed.

[0105] o The degradation rate of the polymer caused by bulk hydrolysis

[0106] · The ability of biological substances (such as but not limited to cells, proteins, and enzymes) to adhere to the fibers or to limit / prevent adhesion to act as an anti-fouling surface;

[0107] · The degradation rate of the polymer caused by surface hydrolysis.

[0108] At the level of fiber interconnection, adjusting the wettability can affect (but is not limited to):

[0109] · The sliding ability of non-physically bonded fibers, through which the frictional force between the fibers will be changed to act as a lubricant and facilitate the mobility of individual fibers

[0110] · The ability of non-physically bonded fibers to slide due to the attractive force between hydrophobic surfaces.

[0111] · The ability of water to penetrate into the fiber interconnections and thus act as a plasticizer / solvent, whereby physical bonding of the fibers can be overcome.

[0112] Relocating non-bonded interconnections or generating new physical bonded interconnections before, during, or after implantation can be beneficial for improving mechanical support and for shaping purposes to include, for example, sinusoidal, convex / concave shapes, bends, and / or shaped holes to enable access to side branches, etc. Additionally, this would be an attractive method for pre-forming other types of fibrous structures (such as heart valve geometries). Shaping would require additional constraints to induce the desired geometry and would require additional annealing steps. The relocation or generation of new interconnections can be achieved in several ways, but not limited to: heat treatment, chemical treatment, photoactivation, or ultrasound activation, etc., in vivo or in vitro.

[0113] The present invention also describes methods for modulating the wettability of the fiber network and promoting fiber rearrangement.

[0114] Methods for promoting fiber network rearrangement

[0115] Surface treatment

[0116] The fiber network can undergo high-energy surface treatment (such as plasma, ultraviolet light, or radiation) to cause changes at the chemical and physical levels on the polymer surface. This increases surface wettability when exposed to an aqueous environment. This will facilitate the rearrangement of the fiber network.

[0117] Surface coating

[0118] In addition to surface treatment, coating the fibers with a hydrophilic material can also increase wettability when exposed to an aqueous environment. It should be considered that the coating can greatly affect the mechanical integrity of the fiber conduit, where the coating can act as a lubricant or adhesive when applied to fiber graft applications.

[0119] Increasing temperature

[0120] The ambient temperature at which fiber conduit diameter expansion occurs also affects the wettability of the aqueous solution on the polymer fiber surface, where a higher temperature will improve this effect. The aqueous solution can be water or blood, with or without alcohol mixed. The effect of temperature on wettability is greater for low alcohol concentrations and short-chain alcohols compared to high alcohol concentrations and long-chain alcohols. Therefore, temporarily increasing the temperature at the implantation site can make the rearrangement of the fiber network easier.

[0121] Alcohol as an additive to the aqueous solution

[0122] Alcohols are good additives for increasing the wettability of hydrophobic polymer surfaces in aqueous solutions. Longer alcohol chains can gradually enhance this effect by reducing the surface tension of the aqueous solution and / or binding the alcohol molecules to the defects of the fibers. In other words, by adding alcohol to the aqueous solution, a solvent film will form on the fiber surface, which will enhance the fluidity of the fibers, making it easier for the fibers to rearrange and facilitating the expansion of the conduit diameter. When the preferred diameter is reached, the medium can be replaced or removed from the alcohol to reverse the effect.

[0123] Using alcohols (such as ethanol) can also have a swelling effect on the surfaces of several polymers; thus disrupting the joints that bond the fibers before or during the application of strain. This can improve fiber fluidity and make it easier for the fiber network to rearrange, allowing them to slide past each other, and should be understood as a significant increase in the stretchability of the construct. After removing the alcohol from the aqueous solution, the swelling will be reversed and the bonding of the fibers can be restored, which is caused by the evaporation of the solvent and the accompanying adhesion and interaction between the solvated polymer chains at the anchoring sites. In this way, the stretchability of the fiber conduit can be temporarily increased during diameter expansion, and the structural support can be restored after removing the alcohol from the medium.

[0124] In addition, using alcohols can have a plasticizing effect on the material by affecting the glass transition temperature (Tg) and / or the melting temperature (Tm) and their respective enthalpies of fusion (ΔHm). This can enhance the flexibility of the fibers and contribute to making the construct more stretchable.

[0125] Alcohols can be incorporated into the fiber tubular construct by immersing the graft in an aqueous alcohol solution or by incorporating an alcohol gel within the structure. Such a gel can be produced by separately spinning fibers of a poly(ethylene glycol) (PEG)-based polymer (which has the ability to form hydrogels) in addition to the base material fibers (i.e., PLA) and immersing the construct in an aqueous alcohol solution to form the gel prior to implantation. The benefit of the alcohol gel is that it remains stable within the construct for some time during the implantation process, promoting the stretchability of the structure to allow for diameter expansion. At the final diameter and through gel dissolution, the structure will regain its load-bearing function.

[0126] Adjusting the polymer composition

[0127] By acting on the polymer composition, it is possible to make it easier for the fiber network to rearrange. Incorporating components with different mechanical properties (such as elongation at break or elastic modulus) can enhance the tensile properties.

[0128] Alternatively, a blend polymer or a mixed polymer or a copolymer that produces components with different hydrophobic or hydrophilic characteristics can be incorporated to alter the wettability of the fibers, making the fiber rearrangement simple without compromising the structural ability of the construct. This method is more consistent with the in vivo scenario, where adding alcohol during dilation is less preferred.

[0129] Other methods of facilitating fiber network rearrangement without affecting the wettability of the fiber network are to reduce the strain rate during catheter diameter expansion during implantation. Reducing the strain rate will facilitate the rearrangement of the fiber network

[0130] Methods of testing / evaluating

[0131] The degree of wetting can be measured by analyzing the contact angle (Θ) of a droplet on a solid surface. A high contact angle means the surface is hydrophobic. A low contact angle means the surface is hydrophilic, indicating good wettability of the surface relative to the liquid. By placing a droplet on a solid surface, Θ can be visualized by microscopy and quantified by imaging. The improvement in stretchability can be evaluated using mechanical analysis (e.g., uniaxial tensile testing). Improved stretchability is expected to result in enhanced elongation at break and reduced force required to stretch the fibrous structure. In addition, the appropriate performance and function of the construct can be evaluated by implantation in an animal model and subsequent follow-up, where the construct must demonstrate the ability to be as capable as a minimally invasively deliverable scaffold and as capable as a framework capable of inducing tissue formation, and thus as a regenerative scaffold

[0132] Example 1

[0133] A 2-mm electrospun PLA-based tubular graft was immersed in an ethanol solution and then dilated with a balloon to double its diameter. The tube was dried to evaporate the alcohol, and the construct showed a load-bearing capacity comparable to that of metallic stent substitutes of similar dimensions reported in the literature( Figure 8 )

[0134] Example 2

[0135] To evaluate the effect of alcohols on the wettability of PLA in an aqueous environment, solutions of alcohols with increasing chain length at the time of preparation and the resulting contact angles formed on a solid PLA surface were compared with pure water. Adding pure water to the PLA substrate resulted in a contact angle of 85°( Figure 9A ), which decreased to 60° after including 25% methanol( Figure 9B ), to 45° with 25% ethanol( Figure 9C ), and to 20° with 25% 1-propanol( Figure 9D )

[0136] Example 3

[0137] The effect of alcohols on the stretchability of PLA-based fibrous tubular conduits was evaluated by uniaxial tensile tests at room temperature. One hour after spinning, 0.5-mm-wide rings were obtained from 20-mm electrospun PLA tubes. The samples were immersed in pure water and 25% alcohol solutions of interest and tested at a strain rate of 2.33 mm / s. Compared to pure water, the addition of methanol led to a 2.5-fold increase in the elongation at break, while the addition of ethanol increased it 3.67-fold, and the addition of 1-propanol even prevented the rings from rupturing( Figure 10 ).

[0138] Example 4

[0139] The effect of alcohols on the mechanical properties of PLA-based fibrous tubular conduits after alcohol depletion was studied using uniaxial tensile tests at room temperature. The tests were carried out on: i) dry electrospun rings, ii) rings immersed in pure water, iii) rings immersed in 25% ethanol solution and iii) rings immersed in 25% ethanol solution and depleted of water by multiple washing steps in water. This example shows that ethanol has an effect on the mechanical properties of PLA-based fibrous tubular conduits, which is to some extent reversible( Figure 11 ). Testing the dry PLA-based rings demonstrated the advantage of the electrospinning technique for stretchability. The electrospun PLA had a two-order-of-magnitude increase in elongation compared to the elongation at break of the bulk PLA. When the samples were immersed in water, the force decreased, and an even more significant decrease was observed when immersed in the ethanol solution. After depleting the ethanol, the force recovered to a value comparable to that of water immersion.

[0140] Example 5

[0141] The strain rate plays an important role in the mechanical properties of the PLA-based scaffolds. The uniaxial tensile tests on PLA-based rings were repeated with the tensile speed reduced to 0.023 mm / s( Figure 12 ). Reducing the strain rate allows the fibers to reorganize and relax, improving the stretching ability of the constructs.

[0142] Example 6

[0143] Regenerated scaffolds were enhanced in stretchability by adding alcohol to the aqueous solution expanding the constructs (Figure 7A). The constructs could be transformed from state 1 to state 2 without compromising their integrity during expansion (Figure 7A). The diameter expansion achieved during balloon inflation is plotted in Figure 7B. The fiber dispersion values and histograms corresponding to the two states are plotted in Figures 7C, 7D, 7E, and 7F.

[0144] Example 7

[0145] Regenerated scaffolds were enhanced in stretchability by acting on a polymer composition delivered minimally invasively via balloon dilation in the abdominal aorta of rats( Figures 18A to 18C)。This example illustrates a method of treating vascular diseases using an embodiment of the present invention. A stent has been successfully deployed in a natural artery by a minimally invasive method ( Figure 18A )。In addition, cells are able to infiltrate the construct and start producing tissue two weeks after implantation ( Figures 18B to 18C )。The regenerative stent has expanded independently of the strut pattern and maintains its supporting ability after implantation without compromising its integrity.

[0146] Method of Use

[0147] Various clinical indications can highly benefit from regenerative stents and bioabsorbable stents that lack a strut pattern ( Figure 19 )。Each specific indication has unique characteristics and requirements to be considered and should be evaluated individually for clarity, which will be further elucidated in some examples.

[0148] Example 1

[0149] Atherosclerosis is a disease that develops due to the deposition of fatty substances (such as cholesterol) in arteries, which causes hardening of the blood vessel walls and narrowing of the arteries. It is believed that the trigger and progression of atherosclerosis are related to inflammatory processes in endothelial cells and / or smooth muscle cells of the blood vessel wall associated with retained low-density lipid (LDL) particles. The current hypothesis is that covering thin-cap fibroatheromatous plaques will induce plaque regression and form a thick isolating mass of covering tissue. Since the regenerative stent will start forming a tissue layer on top of the fibrous cap, it can promote plaque regression.

[0150] Example 2

[0151] An aneurysm is a local weak area that bulges outwards in a blood vessel. When they are filled with blood and subjected to continuous cyclic pressure, aneurysms grow over time and become weaker, and eventually they rupture and cause internal bleeding. The regenerative stent can completely isolate the aneurysm and take over the arterial load. When the blood flow inside the aneurysm is blocked, a thrombus can form to fill the cavity. Over time, new arteries will be generated, and the aneurysm will safely regress as the thrombus is absorbed. Some embodiments may include a fibrous network that can act as a flow diversion device.

[0152] Variants

[0153] In some embodiments, before, during, or after implantation. Markers can be incorporated to enhance traceability through imaging devices. In some embodiments, contrast agents can be included. In some embodiments, the device can be further functionalized by including cell capture portions on the lumen side, inside, or outside the fibrous grid.

[0154] In some embodiments, an agent (e.g., a drug or therapeutic agent) can be incorporated, which can be an immunomodulatory anti-inflammatory drug (e.g., a steroid), an antiproliferative drug (e.g., sirolimus), or a therapeutic, prophylactic, or diagnostic agent. The agent can be an anti-tumor agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombotic agent, an antimitotic agent, an antibiotic agent, an anti-allergy agent, an antioxidant, an anti-infection agent, and a cytostatic agent.

[0155] In some embodiments, the agent can affect biological processes, including but not limited to bioactive agents from whole biological compounds (e.g., cytokines, chemokines, or other enzymes or their peptides of biological or synthetic origin).

[0156] In some embodiments, the construct can be used as an agent carrier. The agent can be incorporated into the fibers by mixing the agent into the polymer solution before production. After production, the agent can be coated on the fiber surface. The agent can be chemically linked to the fiber network. By using supramolecular chemistry, the agent can be chemically linked.

[0157] In some embodiments, once implanted, the agent will be released. The agent can be released when the fibers are absorbed and / or when the coating on the fibers is absorbed over time. The secretion rate of the drug can be controlled by adjusting the degradation rate of the polymer / coating. Similarly, changing the concentration of the incorporated agent will affect the release profile. When the agent is chemically linked, the agent can be released as the chemical linker is disrupted. The disruption of the chemical link can be caused by temperature, pH, ultrasound, additives, or cytokines released by cells. The disruption of the chemical link can occur without further interference, or it can be controlled by specifically inducing a trigger that initiates the disruption of the chemical link.

[0158] In some embodiments, the agent can be incorporated into the embodiments to act on: cell infiltration, cell adhesion, tissue formation, tissue composition, selective cell recruitment, neointimal tissue formation, endothelial cell adhesion, macrophage polarization, cell activation, induction of angiogenesis, induction of plaque regression in atherosclerotic regions, activation of cell contractility, and / or induction of tissue degradation.

[0159] The fiber conduit can be positioned in front of a bifurcation or other opening after implantation, which can impede the passage of biological components. To promote patency of the obstructed area, the wall of the fiber construct can be adjusted. In some embodiments, the medical device can penetrate from the inside through the wall to the outside to reach the bifurcation ( Figure 21A ). The medical device can be a balloon catheter, which can be inflated and induce local rearrangement of the fiber network at the bifurcation position ( Figure 21B)。After the removal of the medical device, the bifurcation remains open. In another embodiment, small holes are created within the wall of the fibrous network before or after implantation. The holes are located in front of the bifurcation and provide patency. When preferred, the holes can be reshaped by a similar medical device (such as a balloon catheter).

[0160] In an exemplary embodiment, two constructs can be mounted on a balloon catheter, with a spacing therebetween ( Figure 21C ). After the stent is implanted, this spaced portion can be placed in front of the bifurcation to maintain patency ( Figure 21A ). In another embodiment, two constructs can be mounted on a balloon catheter, with a spacing therebetween, and can include a layer of rapidly absorbable material to cover the spacing. After the stent is implanted, the portion with the spacing covered by the rapidly absorbable material can be positioned in front of the bifurcation, where the rapidly absorbable layer can maintain patency of the bifurcation after absorption.

[0161] The stent can incorporate additional embodiments.

[0162] Additional Embodiment 1:

[0163] The stent can include a valve construct. The valve can include one, two, three, or more leaflets. The valve can be mechanical, biological, or synthetic. The synthetic valve can include a fibrous network. The biological heart valve can be an allograft, autograft, or xenograft. The combined stent - plus - valve embodiments can be used to minimally invasively replace valve structures (such as in the heart or veins). Components of an exemplary valve stent are shown in Figures 20A to 20E . The valve stent can be composed of one or more layers and will require the use of special mandrels and molds to shape the leaflets, as well as surface treatment and annealing steps.

[0164] Additional Embodiment 2:

[0165] The stent can include a cross - sectional membrane. The membrane can be biological, metallic, or synthetic. The membrane can be permeable or impermeable. The membrane can facilitate or prevent fluid exchange. The membrane can facilitate or prevent cell passage or selectively filter cells. Filtration can be achieved by adjusting the pore size of the membrane. Groups can be incorporated into the membrane to selectively adhere to cells, enzymes, or proteins. The membrane can trigger tissue formation. The combined stent - plus - membrane embodiments can be used as filters, to close ducts, or to induce blockages in biological conduits.

Claims

1. A graft, comprising: An expandable construct made of a fiber network, wherein the fiber network is divided into: (i) A first state having a first geometric dimension of the construct determined by a first fiber orientation, the first fiber orientation being characterized by a first fiber dispersion value, a first principal angular difference, and a first average fiber geometric dimension, and (ii) A second state having a second geometric dimension of the construct determined by a second fiber orientation, the second fiber orientation being characterized by a second fiber dispersion value, a second principal angular difference, and a second average fiber geometric dimension, wherein the transition from the first state to the second state is provided only by rearrangement of the fibers in the fiber network; wherein the fiber network in the second state is configured to support a biological conduit; wherein the rearrangement of the fiber network from the first state to the second state is accomplished by: (i) Stretching and / or straightening the fibers in the fiber network; (ii) Sliding, breaking, or a combination thereof of the interconnections of the fibers in the fiber network; (iii) Reorientation and / or realignment of the fibers in the fiber network; or (iv) A combination of (i), (ii), and / or (iii); and wherein the fiber network consists of one or more randomly organized stacked fiber layers.

2. The graft according to claim 1, wherein, The first fiber dispersion value is greater than the second fiber dispersion value.

3. The graft according to claim 1, wherein, The first geometric dimension is equal to the second geometric dimension.

4. The graft according to claim 1, wherein, The rearrangement of the fiber network can be facilitated by acting on the wettability of the fiber network to provide a transition from the first state to the second state.

5. The graft according to claim 1, wherein the construct is shaped to induce a change in geometry or opening.

6. The graft according to claim 1, wherein, The construct is made of a bioabsorbable fiber network.

7. The graft according to claim 1, wherein, The first geometric dimension of the construct is smaller than the second geometric dimension of the construct.

8. The graft according to claim 1, wherein, The fiber network in the second state serves as a scaffold.

9. The graft according to claim 1, wherein, The fiber network in the second state allows cell infiltration and / or induces autologous tissue formation.

10. The graft according to claim 1, wherein, The one or more stacked fiber layers have different densities.

11. The graft according to claim 1, wherein, The circumferential alignment of the fibers is facilitated by an increase in the diameter of the construct.

12. The graft according to claim 1, wherein, The graft includes a valve construct and / or a cross-sectional membrane.

13. The graft according to claim 1, wherein, The wall of the construct is adjusted by inducing local rearrangement of the fiber network.

14. The graft according to claim 1, wherein, The rearrangement of the fibers in the fiber network results in alignment of the polymer chains in the fibers.

15. The graft according to claim 1, wherein, The graft is a stent.

16. The graft according to claim 1, wherein, The construct is tubular.

17. The graft according to claim 1, wherein, The geometric dimension of the construct is the diameter.

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