Method for preforming an implantable polymeric luminal support structure - Patents.com

Abstract

The present invention provides a method for preforming an implantable polymeric luminal support structure (20) for delivery and placement within the body, comprising: - forming a microfibrous tubular structure (10) made of polymer fibers, said microfibrous tubular structure (10) having a first diameter; and - compressing the microfibrillary tubular structure (10) to a second diameter, said second diameter being smaller than the first diameter. The present invention relates to a method comprising the steps of:

Description

[Technical field]

[0001] The present invention is in the technical field of implantable polymeric luminal support structures, such as stents and / or scaffolds, for use, for example, in regenerative cardiovascular intervention.

[0002] In particular, the present invention relates to a method for preforming an implantable polymeric stent for delivery and placement within a body lumen, such as a blood vessel. [Background technology]

[0003] No. 10,813,777 discloses a tubular stent made of a bioabsorbable polymer fiber network that can reorganize upon expansion to accommodate diametric expansion without the need for struts or strut patterns and provide temporary support to biological vessels. Additionally, a stent is provided in which the reorganized fiber network, in the expanded state, can act as a scaffold for cell infiltration and promote the formation of autologous tissue.

[0004] In cardiovascular intervention, implantable luminal support structures such as stents can function as minimally invasively deliverable scaffolds.

[0005] It is known to use stents having a small diameter initial nominal configuration for delivery and deployment within a body lumen, which are expanded (eg, with inflation of a balloon) after deployment.

[0006] However, this known approach suffers from the drawback that the luminal support structures, particularly polymeric stents, tend to revert to their initial, smaller nominal configuration after deployment and expansion.

[0007] A known solution is to manufacture a stent according to the size it is to have and maintain after being deployed at a target site within a body lumen (e.g., a blood vessel) and then compress the stent to a smaller diameter for deployment purposes.

[0008] In particular, the stent is subjected to a crimping procedure using a crimping device which applies a radial compression that reduces the diameter of the stent.

[0009] After the stent is positioned at the desired target site within the body lumen, the diameter of the stent is then radially expanded, for example by self-expanding or by inflating a balloon.

[0010] Compression devices are known in the art and, in the case of balloon-expandable stents, typically include a balloon of a catheter assembly within the lumen for compressing the stent onto such balloon. The stent is centrally positioned in the device and then compressed by applying radial compression, which reduces the diameter of the stent to a desired size and allows the stent to be securely mounted onto the balloon of the catheter assembly.

[0011] Delivery and deployment of a stent is typically accomplished by placing the stent around one end of a catheter, inserting said end of the catheter into a body lumen (e.g., a blood vessel), advancing the catheter to the target site, expanding the stent at the target site, and finally removing the catheter from the lumen (U.S. Pat. No. 8,298,466).

[0012] A stent must be capable of being compressed and expanded without structural and / or functional damage to its structure.

[0013] Additionally, once deployed at the target site, the stent must maintain its size and shape despite the loads and forces exerted on it after deployment.

[0014] For example, after being deployed and expanded at a target site in a blood vessel, a stent must withstand radial forces exerted by the walls of the blood vessel in addition to cyclic loads induced by the beating of the heart or the movement of arteries in the body (especially in the legs or other extremities).

[0015] U.S. Patent No. 8,298,466 discloses a method for producing a stent with improved mechanical support capability against the wall of a body lumen, comprising the steps of placing a bioabsorbable polymer tube in a chamber; contacting the tube with a fluid in a supercritical state, the fluid being impregnated into the polymer tube; adjusting conditions in the chamber such that the fluid is in a subcritical state, forming a porous structure in the tube; and reducing or preventing radial expansion of the tube during formation of the porous structure.

[0016] US2017348124 discloses a method for uniformly compressing and expanding a medical device such as a scaffold. A catheter balloon is pressurized at a relatively high pressure prior to compression such that pre-organized balloon pleats are substantially removed. Then, when the balloon reaches an inflated state, the scaffold is compressed onto the balloon until the diameter of the scaffold is reduced by about 50% (or more). At this point, the balloon pressure is relieved to avoid damaging the balloon and achieve a small crossing profile.

[0017] US2017252191 discloses a method for compressing a polymer-coated stent onto a balloon catheter. The stent may be a metal stent or a bioabsorbable polymer stent having a coating comprising a polymer and a rapamycin derivative drug. Compression is performed in an environment with a relative humidity of 45% to 55% and a temperature above 25 degrees, and the humidity is maintained until the stent is compressed onto the balloon by the compression device and is considered to be shrunk.

[0018] However, there is still room for improvement.

[0019] In particular, there is a need to improve the ability of luminal support structures, such as stents, to maintain their size and shape after deployment and to improve the adhesion of the structures to the walls of body lumens, e.g., blood vessels, thereby preventing the risk of undesirable displacement after deployment. Summary of the Invention

[0020] This object is achieved by the provision of a method for preforming an implantable luminal support structure as claimed in claim 1.

[0021] Accordingly, there is provided a method of preforming an implantable polymeric luminal support structure for delivery and placement within the body, comprising: - forming a microfibrillar tubular structure of polymer fibers, the microfibrillar tubular structure having a first diameter; and - compressing the microfibrillar tubular structure to a second diameter, the second diameter being smaller than the first diameter; A method is provided, comprising:

[0022] In particular, the present invention provides methods for preforming an implantable luminal support structure for delivery and placement within the body, particularly within a body lumen such as a blood vessel.

[0023] The luminal support structure can be, for example, a polymeric microfiber stent.

[0024] The tubular structures are preferably made of a network of polymeric fibers in the micrometer or nanometer range, see especially US Patent No. 10,813,777.

[0025] In particular, the tubular structure may be a stent obtained by electrospinning.

[0026] The present invention is based on the fundamental concept that by providing a luminal support structure made from polymeric fibers, it is possible to obtain an improved implantable structure (e.g., a polymeric stent) that, once deployed, has an improved ability to maintain its size and shape, regardless of the loads and forces acting on it while in situ, said structure further exhibiting an improved ability to adhere to the wall of the body lumen, e.g., blood vessel, in which it is deployed.

[0027] In particular, the main concept is that a support structure, such as a stent structure, is compressed from a larger first diameter to a smaller second diameter. Stent structures, such as those described in U.S. Pat. No. 10,813,777, have shape memory, i.e., they (can) return to their initial shape due to certain temperature and environmental factors, such as the presence of water or other substances. This prevents the situation in which the stent structure tends to return to its initial configuration (the configuration before it was deployed and expanded to adhere to the inner wall of the blood vessel) after implantation, which may mean that the stent structure returns to a smaller diameter and therefore cannot maintain its position within the vessel.

[0028] According to the basic concept of the present invention, the stent is initially provided with a nominal length and diameter, and is then compressed to a smaller diameter and then used for deployment. Upon deployment, the stent returns to its nominal, i.e. normal, length and diameter. In this size and configuration, it is placed at the implantation site in the blood vessel. Further effects of temperature, water absorption, and other influencing factors that may cause the stent structure to return to its nominal state and configuration cannot cause further shrinkage of the stent since the stent is already implanted and deployed in its nominal state.

[0029] The inventors have seen the problem of stent-specific recoil with a fully polymeric microfibril structure (stent). Here, the stent (without being subjected to the method of the present invention) was first made in a small diameter form, expanded, and exposed to elevated physiological temperatures (exothermic conditions). The stent then returned to its small nominal diameter form. The stent seems to have a defect of "shape memory effect" and tries to return to its nominal form when exposed to elevated physiological temperatures in an aqueous environment. This led to the problem that the stent becomes smaller after the balloon is removed, and therefore the stent itself causes stenosis in the artery. As a solution, the inventors realized that the stent should be provided in the size (new nominal state) that it should be at the implantation site. Then, when the stent is compressed and then expanded and exposed to high temperatures, the stent tries to return to its initial state again, but this time with a larger diameter. In this way, the stent does not shrink at the implantation site. This has already been confirmed and proven in the laboratory. In this way, the structure can be influenced so that when a factor that induces a shape memory effect is applied, the stent structure will in any event return to its pre-compressed shape, and also helps to avoid undesirable irreversible structural or material changes during the process.

[0030] Preferably, the compression is performed at a temperature below the glass transition temperature (T g ) In this temperature range, the shape memory of the stent structure and its material can be set very well.

[0031] More preferably, the compression is carried out at room temperature.

[0032] For example, compression may be carried out at a temperature ranging from 34°C to 43°C.

[0033] In particular, compression may preferably be performed at about 37° (ie, about the body temperature of a healthy human subject).

[0034] For carrying out the method, a temperature range at so-called nominal physiological conditions is preferred, in order to ensure that the material is treated by the method in the temperature range that also applies after implantation.

[0035] Advantageously, the compaction may be carried out in an environment having a humidity level of about 20% to 100%.

[0036] For example, the pressing can be carried out in an aqueous solution, however, it is also possible to carry out the pressing step in a dry state, in the absence of an aqueous solution.

[0037] For example, compacting may include performing compaction of wetted microfibrillar tubular structures.

[0038] Adding an aqueous solution or carrying out the method at a particular humidity can increase the glass transition temperature (T g ) which can further enhance the structural characteristics of the stent resulting in improved ability to compress the stent.

[0039] In particular, said aqueous solution may be water. In the tests, normal drinking water was used. It is also possible to use isotonic water, saline or phosphate buffered saline, which are compatible with the physiological conditions of the solutes in humans.

[0040] The method may further include leaving the microfiber tubular structure in a compressed state after compression and before releasing, which allows for relaxation of the fibers due to compression.

[0041] If compression is performed in an aqueous solution (eg, water), the step of leaving the microfibrillary tubular structures in a compressed state may be performed while immersed in the aqueous solution.

[0042] Furthermore, when the compression is carried out in an aqueous solution at a relatively high temperature (e.g., in the range of 34° to 43°, preferably around 37°), the method comprises the steps of: - removing the microfibrillar tubular structures from the aqueous solution; and - While maintaining the compressed state, the microfibrillary tubular structure is heated to the glass transition temperature (T g ) cooling to below may include.

[0043] Thereafter, the compressive load can be released and the microfibrillar tubular structures are allowed to dry.

[0044] Alternatively, the microfiber tubular structures may be dried before the compressive load is released.

[0045] For example, drying of the electrospun tubular structures (either before or after release of the compressive load) can be carried out using compressed air.

[0046] A support structure, such as a stent, typically comprises a porous structure made of a hydrophobic polymeric material.

[0047] Thus, when exposed to water or bodily fluids such as blood, air remains trapped in the porous structure, inhibiting the penetration of water or bodily fluids.

[0048] The inventors have found that wetting the microfibrillar tubular structure prior to compression is beneficial as it facilitates rearrangement of the fibrous mesh and makes expansion easier. Additionally, infiltration of the structure with a material may promote and facilitate cell infiltration into the structure, prevent air embolism that is trapped within the structure and released after implantation, support coatings, or even be used as a carrier for pharmaceuticals. Additionally, wetting helps the entire stent structure have homogenous stent expansion properties.

[0049] Stent structures made from the polymer fibers described herein in this disclosure have surprisingly been found by the inventors to have such shape memory that they tend to return to their original state. This is particularly true for stents that have a "dry" glass transition temperature (T g ) and "wet" glass transition temperature (T g The polymers used have a T above body temperature. gThis means that at body temperature the polymer is in a glassy state, which means the material is hard, brittle, and strong. Since stent construction mainly uses tiny fibers, water can strongly affect the hydration of the fibers used in stent construction. When water molecules start to interfere with the polymer chains in the fibers, this causes the T g This can lead to a rapid decline in T g decreases until it reaches physiological body temperature. Here, the polymer goes through a glass transition to a rubbery state. This allows the polymer chains to move freely again. What happens next is that this allows the accumulated stress and strain caused by the compressive deformation to dissipate, thereby returning to the initial strain-free and stress-free (or more optimal) starting shape.

[0050] This is because the stent structure is dry and the dry T g It also explains that it will maintain its compression as long as it is exposed to temperatures below T. However, as soon as the structure becomes damp, the T g decreases and regains the "shape memory" effect.

[0051] To this end, the method may further comprise subjecting the microfibrous tubular structures to high centrifugal forces while immersed in an aqueous solution, preferably water, prior to compression, such that air is removed from the network of electrospun polymer fibers and replaced with the aqueous solution.

[0052] In particular, said aqueous solution may be water.

[0053] High centrifugal force may be applied, for example, at a relative centrifugal force (RCF) of 15,000×g for approximately 30 seconds.

[0054] The compression is performed with the tubular structure already fitted around the expandable balloon of the catheter assembly. In this way, the manufacturing process of a ready-to-implant and ready-to-deploy product is significantly enhanced. In any case, some kind of compression or the like is required to place the stent structure on the balloon. Therefore, there is only one compression step that integrates the setting of the dimensions of the balloon catheter and the fitting on the balloon. Therefore, a compression method may be used to mount the stent on the balloon catheter device. In any case, it is important that the stent is tightly compressed on the balloon. Therefore, after compression, the stent should not expand (gradually) during the storage period or during delivery into the body. Also, it should be firmly fixed so that it can withstand the "removal forces" when pushing it through a narrow, rough, calcified lesion or when advancing it through an introduction device. This is achieved in the manner described above.

[0055] The invention further provides a microfibrillary tubular structure having the features of claim 15.

[0056] The microfibrillar tubular structures have a first configuration before compression and a second configuration after compression, the compression being effected by the methods described above.

[0057] In particular, the microfibrillar tubular structures include: (i) a first state having a first diameter of the microfibrillar tubular structure (10) in a first configuration before compression, the microfibrillar network being determined by a first fiber orientation characterized by a first fiber distribution and a first principal angle difference, and a first average fiber diameter; and (ii) a second state having a second diameter of the microfiber tubular structure (10) in a second configuration after compression, the microfiber network being determined by a second fiber orientation characterized by a second fiber distribution and a second principal angle difference, and a second average fiber diameter; wherein the second diameter of the microfibrillary tubular structure is smaller than the first diameter of the microfibrillary tubular structure.

[0058] The microfiber network may be organized according to a random fiber orientation scenario.

[0059] In this case, the first fiber distribution is less than the second fiber distribution.

[0060] Alternatively, the microfibril network may be organized according to a controlled fibre orientation scenario.

[0061] In this case, the first principal angular difference is equal to or smaller than the second principal angular difference.

[0062] Alternatively, the microfiber network may be organized according to a combination of controlled and random fiber orientation scenarios.

[0063] Alternatively, the microfiber network may be composed of multiple layers of controlled or random fiber orientation, or a combination of both.

[0064] Advantageously, in the first configuration before compression, the polymeric fibres forming the network are organised according to a circumferentially aligned configuration.

[0065] When the microfiber tubular structure is re-expanded to its original state after placement at the target site, the same arrangement of polymer fibers is obtained.

[0066] This allows for increased load-bearing capacity of the microfibrillar tubular structures and for native-like tissue formation: in particular, cells can align along the fibres of the structures and produce tissue components (e.g. collagen) in the same direction, mimicking the native morphology.

[0067] In the first configuration, before compression, the microfibrillary tubular structure may have an inner diameter of 100 mm or less.

[0068] In the second configuration after compression, the microfibrillar tubular structures may have an increased wall thickness than in the first configuration before compression.

[0069] And when re-expanded to its original state after deployment at the target site, the wall thickness of the microfibrous tubular structures decreases again.

[0070] Furthermore, in the second configuration after compression, the microfibrillar tubular structures may have substantially the same length as in the first configuration before compression.

[0071] Thus, in accordance with the present invention, the wall thickness of the microfibrous tubular structure may change between the first and second configurations, while the length of the microfibrous tubular structure remains substantially unchanged.

[0072] The material of the implantable polymer stent can be a biocompatible polymer. Biocompatible polymer fiber materials are in particular: - bioabsorbable polymers (e.g. polylactic acid (PLA), including poly(L-lactide), poly(D-lactide), poly(D,L-lactide), and copolymers thereof, such as polyglycolide, polycaprolactone, polydioxanone, poly(trimethylene carbonate), poly(4-hydroxybutyrate), poly(ester amide) (PEA), polyurethane, poly(trimethylene carbonate), poly(ethylene glycol), poly(vinyl alcohol), polyvinylpyrrolidone, and copolymers thereof, such as poly(L-lactide / DL-lactide), poly(L-lactide / D-lactide), poly(L-lactide / glycolide), poly(L-lactide / caprolactone), poly(DL-lactide / glycolide), - non-bioabsorbable materials (such as polypropylene, polyethylene, polyethylene terephthalate, polytetrafluoroethylene, polyaryletherketone, nylon, fluorinated ethylene propylene, polybutester, silicone, or copolymers thereof); - Biological components (such as hyaluronic acid, collagen, gelatin, chitosan, alginate, aloe / pectin, cellulose or other biological substances derived from tissues, whether autologous, allergenic or xenogeneic); - or a combination of these These may include, but are not limited to:

[0073] Advantageously, the polymeric fibers may comprise poly(L-lactide), poly(D-lactide), polyglycolide, or combinations thereof in the form of copolymers, either poly(DL-lactide), poly(lactide-co-glycolic acid), or poly(DL-lactide-co-glycolic acid).

[0074] In particular, the crystalline or semi-crystalline polymeric material has a glass transition temperature (T g ).

[0075] Further details and advantages of the invention are disclosed below in conjunction with the drawings.

[0076] It is shown below: [Brief description of the drawings]

[0077] [Figure 1] FIG. 1a: an implantable luminal support structure, particularly a stent, before and after a compression step according to an embodiment of the present invention; FIG. 1b: a view similar to FIG. 1a, but from a different perspective; [Diagram 2] After compression, the microfiber tubular structure is cooled to room temperature while still under compressive load; [Diagram 3] Figure 3a-3e: Procedures for removing air from the microfibrous tubular structures by applying high centrifugal force and hydrating the microfibrous tubular structures with an aqueous solution; [Figure 4-1] 4a-4f: Different views of the arrangement of polymer fibers forming a microfibrillar tubular structure in a first configuration before compression and a second configuration after compression, respectively, in an exemplary embodiment in which the polymer fibers are arranged according to a random fiber orientation scenario; [Figure 4-2] Same as Figure 4-1. [Diagram 5]5a-5b: Different views of the arrangement of polymer fibers forming microfibrillary tubular structures in a first configuration before compression and a second configuration after compression, respectively, in an exemplary embodiment where the polymer fibers are arranged according to a controlled fiber orientation scenario; [Figure 6] Figure 6a-6c: Image analysis based on images obtained by microscope showing how the principal angle and distribution of the polymer fibers change when going from a first morphology before compression to a second morphology after compression, when the polymer fibers are arranged according to a random fiber orientation scenario; [Figure 7] Figure 7a-7c: Image analysis based on images obtained by microscope showing how the principal angle and distribution of the polymer fibers change when going from a first morphology before compression to a second morphology after compression, when the polymer fibers are arranged according to a controlled fiber orientation scenario; [Figure 8] Schematic diagram of the inherent recoil problem of stents (prior art); [Figure 9] Schematic diagram of the inherent expansion of a stent according to the present invention; [Figure 10] An example of stent-specific recoil shown in Figure 10 (top of Figure 12) and an example of stent-specific expansion according to Figure 11 (bottom of Figure 12); [Figure 11] FIG. 1 is a graph showing the glass transition temperature Tg of a polymer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0078] The present invention provides a method for preforming an implantable polymeric luminal support structure 20 for delivery and placement within the body, particularly within a body lumen such as a blood vessel.

[0079] In this embodiment, the luminal support structure 20 is a stent 20 .

[0080] For example, the stent 20 may be obtained by electrospinning.

[0081] By "stent" is intended a structure for providing structural support to a body lumen, such as a blood vessel, following deployment at a target site, either self-expanding or balloon-expanding.

[0082] The method includes forming a microfibrous structure 10 made of a network of electrospun polymer fibers, said tubular structure 10 having a first diameter. The method further includes compressing the so obtained microfibrous tubular structure (10) to a second diameter, said second diameter being smaller than the first diameter.

[0083] 1a and 1b respectively show a stent 20 in a first configuration prior to deployment and in a second configuration for deployment, in which the microfibrillary tubular structure 10 forming the stent 20 has been compressed to a smaller diameter.

[0084] The present invention makes it possible to obtain an improved luminal support structure 20, such as a stent 20, which has an improved ability to maintain its size and shape after deployment and which, once deployed, better adheres to the wall of a body lumen, e.g., a blood vessel, thereby preventing undesirable displacement from occurring.

[0085] The compression is performed at a temperature above the melting transition temperature (T m ), preferably below the glass transition temperature (T g ), more preferably at room temperature.

[0086] In particular, compression may be carried out at a temperature ranging from 34°C to 43°C, preferably at about 37°C.

[0087] Compression may be performed in an environment having a humidity level of about 20% to 100%.

[0088] In this embodiment, the compression is carried out in an aqueous solution.

[0089] In this embodiment, the aqueous solution is water, for example tap water or drinking water.

[0090] In particular, in this embodiment, compression is carried out in said aqueous solution at a temperature ranging from 34°C to 43°C.

[0091] Preferably, compression is carried out in said aqueous solution at about 37° C., ie, a temperature close to the body temperature of a healthy human being.

[0092] After compression, the microfiber tubular structure 10 is allowed to remain in a compressed state before being released.

[0093] This allows for relaxation of the polymer fibers due to compression.

[0094] In this embodiment, the step of leaving the microfibrous tubular structure 10 in a compressed state is performed while immersed in said aqueous solution.

[0095] In particular, in this embodiment, compression is carried out in said aqueous solution at a relatively high temperature.

[0096] In particular, in this embodiment, the method further comprises: - removing the microfibrillar tubular structures 10 from said aqueous solution; and - allowing the microfibrillary tubular structure 10 to cool at room temperature while still in compressed state. Includes.

[0097] By "relatively high temperature" is intended a temperature in the range of 34°C to 43°C, preferably about 37° (ie, the body temperature of a healthy human).

[0098] By "room temperature" is intended a temperature of about 20°.

[0099] FIG. 2 shows the microfiber tubular structure 10 after compression cooled at room temperature (eg, about 20° C.) while the compressive load is still acting on the structure 10 .

[0100] Wetting the microfibrous tubular structure 10 prior to compression is beneficial as it facilitates rearrangement of the fibrous mesh, making expansion easier.

[0101] 3a-3e show a procedure for removing air from the microfibrous tubular structure 10 by applying high centrifugal force and hydrating the microfibrous tubular structure 10 with an aqueous solution.

[0102] In particular, in this embodiment, the microfibrous tubular structure 10 is subjected to high centrifugal forces while immersed in an aqueous solution, preferably water, prior to compression, such that air is removed from the polymer fibers and replaced with the aqueous solution.

[0103] In the illustrated embodiment (FIGS. 3a-3e), the microfibrous tubular structure 10 (FIG. 3a) is immersed in a vial 12 filled with the aqueous solution (FIGS. 3b-3c) and then subjected to high centrifugal force while immersed in the aqueous solution (FIG. 3d).

[0104] For example, the high centrifugal force may be applied at a relative centrifugal force of about 15,000 x g for approximately 30 seconds.

[0105] The microfibrillar tubular structures 10 are then maintained in the vial 12 until they sink to the bottom of the vial 12, meaning that the air present in the fibres has been almost completely replaced by the aqueous solution (Figure 3e).

[0106] The present invention further provides a microfibrous tubular structure 10 having a first form before compression and a second form after compression, the compression being obtained by carrying out the method described above.

[0107] According to the invention, the microfibrillary tubular structures are: (i) a first state having a first diameter of the microfibrillar tubular structure 10 in a first configuration before compression, the microfibrillar network being determined by a first fiber orientation characterized by a first fiber distribution and a first principal angle difference, and a first average fiber diameter; and (ii) a second state having a second diameter of the microfibrillar tubular structure 10 in a second configuration after compression, the microfibrillar network being determined by a second fiber orientation characterized by a second fiber distribution and a second principal angle difference, and a second average fiber diameter; and the second diameter is smaller than the first diameter.

[0108] In one embodiment, the polymer fibers may be organized according to a random fiber orientation scenario (FIGS. 4a-4f).

[0109] 4a-4f respectively show an arrangement of polymeric fibers in a first configuration before laying and a second configuration for laying, where the fibers are laid according to a random orientation.

[0110] The first fiber distribution is less than the second fiber distribution.

[0111] In particular, in the first configuration before compression, the tubular structure 10 has an enlarged diameter with the fibers aligned. The orientation histogram depicts a narrow peak region surrounding one preferred orientation (Figure 6a). This is captured by the value of σ decreasing and the value of a approaching 90 degrees (here the circumferential direction). To demonstrate fiber alignment, the degree of fiber dispersion is quantified by comparing σ in the first configuration before compression (σ1) with σ in the second configuration after compression (σ2) (Figures 6a-6b).

[0112] Once placed at a target site within a body lumen, the stent 20 re-expands (either naturally or upon balloon expansion) to its original state with the fibers substantially aligned.

[0113] In an alternative embodiment, the polymer fibers may be organized according to a controlled fiber orientation scenario (FIGS. 5a-5b).

[0114] 5a-5b show an arrangement of polymer fibers in a first configuration before deployment (FIG. 5a) and in a second configuration for deployment (FIG. 5b), respectively, where the first principal angle difference is equal to or less than the second principal angle difference.

[0115] In the first configuration before deployment (FIG. 5a), the tubular structure 10 has an enlarged diameter. The orientation histogram depicts two narrow peaks near 90 degrees indicating circumferential alignment (FIG. 7a).

[0116] Advantageously, in the first configuration before compression, the polymeric fibres may be organised according to a circumferentially aligned configuration.

[0117] When the stent 20 is re-expanded to its original state after deployment at the target site, the same arrangement of polymer fibers is obtained.

[0118] In said first configuration, before compression, the microfibrous tubular structure 10 may have an inner diameter of 100 mm or less.

[0119] In the second configuration after compression, the microfibrous tubular structure 10 has an increased wall thickness than in the first configuration before compression.

[0120] Furthermore, in the second configuration after compression, the microfibrillar tubular structures have substantially the same length as in the first configuration before compression, as can be seen by observing the stent 20 before and after compression, as shown in FIG.

[0121] That is, the wall thickness of the tubular structure 10 changes between the first and second configurations (due to the "sponge effect"), while the length of the tubular structure 10 remains substantially constant.

[0122] Advantageously, the polymeric fibers may comprise poly(L-lactide), poly(D-lactide), polyglycolide, or combinations thereof in the form of copolymers, either poly(DL-lactide), poly(lactide-co-glycolic acid), or poly(DL-lactide-co-glycolic acid).

[0123] The stent 20 may be mounted over the balloon of a balloon catheter.

[0124] Thereafter, once the stent 20 is positioned at a target site within a body lumen, the balloon is inflated, causing the diameter of the stent 20 to re-expand to its original configuration.

[0125] When the balloon is deflated, the stent 20 does not contract but rather maintains its expanded configuration.

[0126] Alternatively, the stent 20 may be self-expanding.

[0127] Also in this case, after being re-expanded to its original configuration, the stent 20 does not contract but maintains the expanded configuration. Figure 8 is a schematic diagram of a prior art stent 100 with respect to the inherent recoil problem of the stent.

[0128] Here, a stent 100 is provided, for example as described in the prior art, made of an electrospun polymer material, whose diameter in the initial state (see left side of FIG. 8) is smaller than that in the expanded state (see center and left part of FIG. 8).

[0129] At 37 degrees, the stent 100 maintains its shape (see the top right portion of FIG. 8).

[0130] If the temperature is above 37 degrees, the stent 100 may exhibit a problem of recoiling, ie, tending to return to its initial diameter (see the lower right portion of FIG. 8).

[0131] FIG. 9 is a schematic diagram of the inherent expansion of a stent according to the present invention using a stent 20 according to the present invention.

[0132] As shown in the left side of Fig. 9, the stent 20 has a larger stent diameter but a smaller wall thickness before compression. Compression reduces the diameter of the stent 20 compared to its initial state and increases the wall thickness (see the center and left parts of Fig. 9). The stent 20 is then expanded by the balloon of the balloon catheter during deployment to return to its initial diameter (see the middle right part of Fig. 9), again remaining in this state, which is essentially the initial state of the stent 20 (see the right part of Fig. 10).

[0133] Figure 10 shows an example of the inherent recoil of the stent shown in Figure 8 (see the top of Figure 10). The initial state of the stent 100 is 1.2 mm in diameter. It is then expanded to a diameter of 2.0 mm. It was found that at a temperature of 47°C, the stent 100 recoils back to a diameter of 1.2 mm.

[0134] Figure 10 also shows in its lower part the inherent expansion of the stent according to Figure 9. The initial state of the stent 20 is 2.0 mm in diameter. It is then compressed and reduced to a diameter of 1.2 mm. It is then expanded to a diameter of 2.0 mm. It was found that at a temperature of 47°C the stent 20 shows no recoil and therefore remains at a diameter of 2.0 mm.

[0135] Figure 11 shows a diagram of the glass transition temperature Tg of polymers. In the left part and the diagram, the upper curve shows the behavior of crystalline polymers and the lower curve shows the behavior of amorphous polymers. As shown in the right part, below Tg the polymers show an oriented structure, but above Tg the polymers show random orientation. [Explanation of symbols]

[0136] 10 Microfibrillary tubular structures 12 vials 20 Implantable polymeric luminal supports (stents) 100 Stent (prior art)

Claims

1. 1. A method of preforming an implantable polymeric luminal support structure (20) for delivery and placement within the body, comprising: - forming a microfiber tubular structure (10) made of polymer fibers, said microfiber tubular structure (10) having a first diameter; and - compressing said microfibrillar tubular structure (10) to a second diameter, said second diameter being smaller than said first diameter; A method comprising:

2. The compression is performed at a temperature above the melting transition temperature (T ｍ ), preferably below the glass transition temperature (T ｇ 10. The method of claim 1, wherein the method is carried out at or near room temperature, more preferably at room temperature.

3. 3. The method of claim 2, wherein the compression is performed at physiological core body temperature in the range of 34°C to 43°C, preferably about 37°C.

4. 10. The method of claim 1, wherein the compacting is performed in an environment having a humidity level of about 20% to 100%.

5. 5. The method of claim 4, wherein the compaction is carried out in an aqueous solution.

6. The aqueous solution comprises: - water, - Isotonic water; - Saline, or - Phosphate buffered saline 6. The method of claim 5, wherein the selected

7. 5. The method of claim 4, wherein compressing comprises compressing the wetted microfiber tubular structure (10).

8. 10. The method of claim 1, further comprising the step of leaving the microfiber tubular structure (10) in a compressed state after compression and before releasing it.

9. 9. The method of claim 8, wherein the step of leaving the microfibrous tubular structure (10) in a compressed state is performed while immersed in an aqueous solution.

10. - Removing the electrospun microfibrous tubular structure (10) from said aqueous solution; and - While maintaining the compressed state, the microfiber tubular structure (10) is heated to a glass transition temperature (T ｇ ) cooling to a temperature below 4. The method of claim 3, further comprising:

11. 2. The method of claim 1, further comprising the step of subjecting the microfibrous tubular structure (10) to high centrifugal force while immersed in an aqueous solution, preferably water, prior to compaction, so that air is removed from the polymer fibers and replaced with the aqueous solution.

12. 12. The method of claim 11, wherein the high centrifugal force is applied at a relative centrifugal force of about 15,000 x g for approximately 30 seconds.

13. 2. The method of claim 1, wherein compression is performed to attach the microfiber tubular structure (10) to a balloon of a catheter assembly or to load the microfiber tubular structure (10) into a delivery sheath.

14. 2. The method of claim 1, wherein the luminal support structure (20) is a stent (20) obtained by electrospinning.

15. A microfiber tubular structure (10) having a first configuration before compression and a second configuration after compression, the compression being carried out by the method of any one of claims 1 to 14.

16. The microfibrillar tubular structure (10) comprises: (i) a first state having a first diameter of the microfiber tubular structure (10) in the first configuration before compression, wherein the microfiber network is determined by a first fiber orientation characterized by a first fiber distribution and a first principal angle difference, and a first average fiber diameter; and (ii) a second state having a second diameter of the microfiber tubular structure (10) in the second configuration after compression, wherein the microfiber network is determined by a second fiber orientation characterized by a second fiber dispersion and a second principal angle difference, and a second average fiber diameter.

16. The microfiber tubular structure (10) of claim 15, wherein the second diameter of the microfiber tubular structure (10) is smaller than the first diameter of the microfiber tubular structure (10).

17. 16. The microfiber tubular structure (10) of claim 15, characterized in that the microfiber network is organized according to a random fiber orientation scenario, and the first fiber dispersion is smaller than the second fiber dispersion.

18. 16. The microfiber tubular structure (10) of claim 15, wherein the microfiber network is organized according to a controlled fiber orientation scenario, and the first principal angle difference is equal to or smaller than the second principal angle difference.

19. 16. Microfibrous tubular structure (10) according to claim 15, characterized in that in said first configuration before compression, the polymeric fibers forming said network are arranged according to a circumferentially aligned configuration.

20. 16. The microfiber tubular structure (10) of claim 15, characterized in that in the first configuration before compression, the microfiber tubular structure (10) has an internal diameter of 100 mm or less.

21. 16. The microfiber tubular structure (10) of claim 15, characterized in that the microfiber tubular structure (10) has an increased wall thickness in the second configuration after compression compared to the first configuration before compression.

22. 16. The microfiber tubular structure (10) of claim 15, characterized in that in the second configuration after compression, the microfiber tubular structure (10) has substantially the same length as in the first configuration before compression.

23. 16. Microfibrous tubular structure (10) according to claim 15, characterized in that the polymeric fibers comprise a biodegradable material, preferably a crystalline or semi-crystalline biodegradable material.

24. The polymer fiber comprises: - polymers of poly(L-lactic acid), - poly(D-lactide), - poly(DL-lactide), - polyglycolide, - polycaprolactone, or - combinations of these 16. The microfiber tubular structure (10) according to claim 15, characterized in that it comprises a polymer material selected from the group consisting of:

25. The polymer fiber comprises: - poly(L-lactide / DL-lactide), - poly(L-lactide / D-lactide), - poly(L-lactide / glycolide), - poly(L-lactide / caprolactone), poly(DL-lactide / glycolide), or - combinations of these 25. The microfiber tubular structure (10) of claim 24, characterized in that it comprises a polymeric material comprising a copolymer of:

26. The crystalline or semi-crystalline polymeric material has a glass transition temperature (T) above the physiological core body temperature of a human. ｇ 24. The microfiber tubular structure (10) of claim 23, characterized in that it has a

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