Covered stent, particularly for vascular intervention

Abstract

An implantable covered stent (1), the covered stent (1) being expandable in a radial direction (R) from a collapsed state to an expanded state, wherein the covered stent (1) further comprises: a scaffold (2) comprising an inner side (2a) and an outer side (2b), and a tubular inner stent cover (3) arranged on the inner side (2a) of the scaffold (2), the tubular inner stent cover (3) comprising an inner surface (3a) delimiting a lumen (4) of the covered stent (1), wherein the inner surface (3a) of the inner stent cover (3) is a microstructured surface and / or has a surface roughness Rz in the range of from 1.0 to 5.0 µm.

Description

[0001] Covered stent, particularly for vascular intervention

[0002] The present invention relates to an implantable covered stent, particularly for a vascular intervention. A further aspect of the invention relates to a method for manufacturing such a covered stent.

[0003] Particularly, the present invention relates to a covered stent for the targeted minimally invasive treatment of blood-carrying vessels that have an acute perforation or are affected by aneurysms or calcified lesions, for example.

[0004] The development of covered stents has significantly expanded the spectrum of endovascular therapies in recent years. Covered stents are vascular prostheses that have a scaffold (i.e. the stent) and a cover covering the struts and the spaces between the struts, contrary to a coated stent where only the struts are covered but not the spaces between the struts. Originally, covered stents were developed to seal aneurysms or vessel perforations. Today, however, covered stents are also used in revascularization therapies as an alternative to conventional stent systems.

[0005] In contrast to classical drug-eluting stents, in which intimal hyperplasia is to be avoided by pharmacological inhibition of cell proliferation, the membrane of covered s serves as a physical barrier between the inner vessel wall (intima) and the lumen of the vessel. Among others, the following clinical indications for covered stents exist:

[0006] - Perforation of blood-bearing vessels

[0007] - Arteriovenous fistulas,

[0008] - Aneurysms,

[0009] - Calcified lesions, and

[0010] - Lesions with high thrombus burden such as reopening of bypasses and occlusions due to myocardial infarction. Covered stents known in the prior art usually have an outer cover, which means that the internal uneven structures, especially the stent struts, are in direct contact with the blood flow (see Fig. 1A). Especially in the early post-interventional phase, in which endothelialization of the covered stent has not yet occurred, there is thus an increased risk of stent-associated thrombosis.

[0011] The synthetic polymer polytetrafluoroethylene (PTFE) as well as its expanded form (ePTFE), but also polyurethane (PU) and other polymers are frequently used as materials of the membranes of covered stents.

[0012] To assess the clinical success rates of commercial covered stents, Nagaraja et al. (2020) performed a systematic review of adverse outcomes in patients after treatment with covered stents (V. Nagaraja, K. Schwarz, S. Moss, C. Kwok und M. Gunning, „Outcomes of patients who undergo percutaneous coronary intervention with covered stents for coronary perforation: a systematic review and pooled analysis of data“, Catheter Cardiovasc. Interv. 2019;l— 7). In this meta-analysis, 29 studies with data from 725 patients treated with covered stents were reviewed.

[0013] The proportion of patients with chronic total occlusions and percutaneous coronary intervention (PCI) was 16.9% and 11.5%, respectively. A total of 9.2% received intracoronary imaging (optical coherence tomography or intravascular ultrasound) and 6.6% atherectomy. The review essentially compared covered stents with covers made of PTFE (70%), PU (21%), and pericardium. Deaths, serious adverse cardiovascular events, pericardial punctures, and emergency surgery occurred within the entire patient population in 17.2%, 35.3%, 27.1%, and 5.3% of procedures, respectively. The analysis of clinical success rates was performed depending on the material of the cover material used. The materials PTFE, PU and pericardium were investigated in this context. Tab. 1 shows the probability of occurrence of clinical complications in a period of 0 to 85 months after implantation.

[0014] Table 1: Clinical outcomes after endovascular therapy of coronary arteries with covered stents; modified from V. Nagaraja et al.

[0015] A follow-up time point >6 months was achieved by 63% of patients. The data show a high mortality, which seems to be mainly caused by thrombosis and restenosis. The occurrence of restenosis is frequently observed at the stent ends (G. G. Secco, R. Serdoz, I. D. Kilic, G. Caiazzo, A. Mattesini, R. Parisi, G. De Luca, G. Pistis, P. N. Marino, C. Di Mario, "Indications and Immediate and Long-Term Results of a Novel Pericardium Covered Stent Graft: Consecutive 5 Year Single Center Experience," Catheterization and Cardiovascular Interventions, vol. 87(4), pp. 712-719, 2016).

[0016] Based on the above, the problem to be solved by the present invention is to provide a covered stent that aims to minimize at least one of the complications listed above in Table 1, particularly the risk of thrombosis.

[0017] This problem is solved by a covered stent having the features of claim 1. Preferred embodiments of this aspect of the present invention are stated in the corresponding dependent claims and are described below.

[0018] According to claim 1 an implantable covered stent is disclosed, the covered stent being expandable in a radial direction from a collapsed state to an expanded state, wherein the covered stent further comprises:

[0019] - a scaffold for proving a base structure of the covered stent, the scaffold comprising an inner side and an outer side,

[0020] - a (tubular) inner stent cover arranged on the inner side of the scaffold, wherein the (tubular) inner stent cover (3) comprises an inner surface (3 a) delimiting a lumen (4) of the covered stent (1), wherein the inner surface of the inner stent cover is a microstructured surface and / or has a surface roughness Rz in the range of from 1.0 to 5.0 pm.

[0021] The microstructured surface may comprise more than one (intentional) groove along a longitudinal direction of the covered stent. Preferably each of the grooves has a depth of up to 1.0 pm and a distance between the grooves of up to 1 pm and / or a groove width of up to 1 pm.

[0022] The mean roughness depth Rz is the absolute peak to valley of five consecutive individual measurement sections in the roughness profile. According to DIN 4768 a section of standard length is sampled from the mean line on the roughness profile. The distance between the peaks and valleys of the sampled line is measured in one direction. In each measurement section, the extreme values are added to a range and divided by the number of measurement sections. Rz is expressed in micrometers (pm).

[0023] More than one (intentional) groove along a longitudinal direction of the covered stent means that the groove has a maximum deviation from the longitudinal axis of ±10°. An intentional groove is a groove which has been obtained during a microstructuring process.

[0024] Thus, the inner surface of the inner stent cover provides a smooth flow-mechanically optimized surface, which enables for a nearly unhindered blood flow and thus for reduced antithrombogenic properties of the covered stent. Furthermore, particularly, as will be described further below, in certain embodiments, the outer stent cover can serve as a drug reservoir for long-lasting inhibition of in-stent restenosis.

[0025] The inner stent cover of the covered stent covers the struts as well as the spaces between the struts. Thus the inner surface of the inner stent cover has a microstructured surface and / or has a surface roughness Rz in the range of from 1.0 to 5.0 pm in regions covering the struts as well as in regions wherein the cover covers the spaces between the struts.

[0026] Preferably, the inner surface of the inner stent cover does not reproduce the inner side of the scaffold. Thus, the inner surface of the inner stent cover comprises a smooth cross-sectional contour in a plane perpendicular or parallel to a longitudinal axis of the scaffold when the covered stent is in a radially expanded state.

[0027] Delimiting a lumen of the covered stent, means that the inner surface of the inner stent cover faces towards a lumen of the covered stent in a radial direction of the covered stent for the passage of a fluid (such as blood) therethrough when the covered stent is implanted into a human or animal patient.

[0028] In contrast to conventional covered stents, the present invention relates to an optimized covered stent comprising at least an inner stent cover (cf. Fig. IB), which can cover and compensate for unevenness of the scaffold, resulting particularly in optimized flow mechanical properties and ultimately a minimized risk of thrombosis. The inner stent cover can achieve further positive effects such as increased static friction of implant and catheter balloon or mechanical protection of the catheter balloon during the crimping process.

[0029] The scaffold (and therewith the stent) can be a self-expandable scaffold that radially expands from a collapsed or crimped state to an expanded state that the covered stent particularly assumes after being implanted. In the framework of the present invention, the collapsed state is characterized by an outer diameter of the covered stent that is smaller than the outer diameter in the expanded state. The collapsed state can e.g. be generated by crimping the covered stent or by reducing the outer diameter against elastic forces of the covered stent / scaffold (and maintaining the reduced outer diameter by means of a surrounding cover / capsule).

[0030] Alternatively, the covered stent, particularly the scaffold, can be balloonexpandable. Here, the crimped covered stent resides e.g. on a balloon which is inflated at the implantation site, forcing the covered stent / scaffold to radially expand from the collapsed (crimped) state into an expanded state. Furthermore, in certain embodiments, the scaffold can be biostable or biodegradable.

[0031] The covered stent may not comprise an outer stent cover. Thus, the inner stent cover can be the only stent cover of the covered stent (so that the outer side of the scaffold is left uncovered).

[0032] According to an embodiment of the invention, the covered stent can comprise an outer stent cover. The outer stent cover, preferably the inner surface of the outer stent cover, is bonded to an outer surface of the inner stent cover to enclose the scaffold in a form-fitting manner. The outer stent cover of the covered stent can cover the struts as well as the spaces between the struts.

[0033] Particularly, the inner stent cover and the outer stent cover can be formed from different polymers, wherein the bonding is accomplished by using a solvent for dissolving the surfaces of the two covers to be joined that is compatible with both polymers. The inner surface of the inner stent cover may have a smoother cross-sectional contour in a plane perpendicular or parallel to a longitudinal axis of the scaffold than the outer surface of the outer stent cover when the covered stent is in a radially expanded state.

[0034] Furthermore, an outer surface of the outer stent cover comprises an uneven contour along the longitudinal axis of the covered stent / scaffold when the covered stent is in a radially expanded state. The uneven counter of outer surface of the outer stent cover reproduces the outer side of the scaffold. Thus, the uneven contour of the outer surface of the outer stent cover comprises alternating valleys and heights, wherein the respective heights being positioned on a strut of the scaffold and the respective valley between two struts e.g. opposing one another in the direction of the longitudinal axis. Such an uneven counter of the outer surface of the outer stent cover enables an improved grip in a vessel wall compared to a smooth outer surface of the outer stent cover.

[0035] The inner stent cover may comprise a thickness t; in the radial direction of the covered stent and the outer stent cover comprises a thickness t0in the radial direction of the covered stent (particularly in relation to the expanded state of the covered stent), wherein a ratio t;:t0is in the range from 10:1 to 1:10.

[0036] Furthermore, as material for the realization of highly expandable cover structures, a focus is preferably set on ductile polymers. Both biostable and biodegradable materials can be used.

[0037] The inner stent cover may comprise or consist of a (medical-grade) polymer, preferably from a polyurethane or silicone-based elastomer, a biostable polymer, a biodegradable polymer, a polyurethane or silicone-based elastomer, a thermoplastic silicone polycarbonate elastomer, preferably comprising 5 wt% silicone, a polycarbonate aliphatic thermoplastic polyurethane elastomer, a thermoplastic polycarbonate polyurethane polymer, an aliphatic and aromatic polycarbonate-based thermoplastic polyurethane, a thermoplastic silicone polycarbonate polyurethane copolymer, an aromatic polyether-based thermoplastic polyurethanes, a siliconepolyurethane co-polymer or mixtures thereof. Such polymers can enable a high elongation at break as well as low modulus of elasticity.

[0038] In a similar fashion, according to an embodiment, the outer stent cover may comprise or consist of a (medical-grade) polymer, preferably from a polyurethane or silicone-based elastomer, a biostable polymer, a biodegradable polymer, a polyurethane or silicone-based elastomer, a thermoplastic silicone polycarbonate elastomer, preferably comprising 5 wt% silicone, a polycarbonate aliphatic thermoplastic polyurethane elastomer, a thermoplastic polycarbonate polyurethane polymer, an aliphatic and aromatic polycarbonate-based thermoplastic polyurethane, a thermoplastic silicone polycarbonate polyurethane copolymer, an aromatic polyether-based thermoplastic polyurethanes, a silicone-poly urethane co-polymer or mixtures thereof.

[0039] According to a further embodiment of the invention, the inner and the outer stent cover can comprise the same material or can consist of the same material (particularly selected from the lists above). Alternatively, in an embodiment, the inner and the outer stent cover can comprise a different material compared to one another or can be formed from a different material compared to one another.

[0040] Furthermore, according to an embodiment of the invention, the inner stent cover comprises a first end (with respect to the longitudinal axis of the scaffold / covered stent), wherein the inner stent cover comprises a first end section ending with said first end, and wherein when the covered stent is in the expanded state, a thickness of the first end section in the radial direction of the scaffold / covered stent decreases along the longitudinal axis of the covered stent towards said first end. At the same time, particularly, an inner diameter of the lumen surrounded by the first end section of the inner stent cover increases towards the first end such that the lumen of the stent transitions in a smooth fashion into the lumen of the vessel into which the covered stent is to be implanted. Particularly, the inner stent cover comprises a middle section connected to the first end section, wherein the inner diameter of the lumen and / or thickness of the inner stent cover is essentially constant in the middle section of the inner stent cover. Furthermore, in an embodiment, the first end section of the inner stent cover can protrude from a first end of the scaffold in a direction of the longitudinal axis of the covered stent.

[0041] According to yet another embodiment, the thickness of the inner stent cover in the first end section decreases one of: linearly, non-linearly, exponentially, in a polynomial fashion, logarithmically.

[0042] Furthermore, according to an embodiment, in a similar fashion, the inner stent cover can further comprise a second end (with respect to a longitudinal axis of the covered stent / scaffold) opposing the first end, wherein the inner stent cover comprises a second end section ending with said second end, and wherein when the covered stent is in the expanded state, a thickness of the inner diameter decreases in the second end section along a longitudinal axis of the covered stent towards said second end. Further, in an embodiment, the second end section of the inner stent cover is connected to the middle section, so that the middle section of the inner stent cover is arranged between the first and the second end section of the inner stent cover. Furthermore, the second end section of the inner stent cover can protrude from a second end of the scaffold in a direction of the longitudinal axis of the covered stent, wherein the second end of the scaffold is arranged opposite the first end of the scaffold. Furthermore, as before, the decrease of the thickness of the inner stent cover in the second end section of the inner stent cover can behave as described in conjunction with the first end section (see above).

[0043] Furthermore, the first end section of the inner stent cover can be bonded to a corresponding first end section of the outer stent cover that can cover the first end section of the inner stent cover completely up to the first end of the inner stent cover. Likewise, the second end section of the inner stent cover can be bonded to a corresponding second end section of the outer stent cover that may cover the second end section of the inner stent cover completely up to the second end of the inner stent cover.

[0044] The covered stent may be a drug-eluting covered stent. The inner stent cover and / or the outer stent cover of the covered stent may comprise a pharmaceutical agent.

[0045] According to yet another embodiment of the covered stent, the outer stent cover is configured to release a pharmaceutical agent in an implanted state of the covered stent.

[0046] Preferably, according to an embodiment, while the outer stent cover is configured to release said pharmaceutical agent, the inner stent cover can be configured to not release a pharmaceutical agent at all.

[0047] According to a further embodiment, the inner stent cover is configured to release a pharmaceutical agent. Particularly, in an embodiment, the pharmaceutical agent released by the outer stent cover can be different from the pharmaceutical agent released by the inner stent cover. Furthermore, according to a preferred embodiment, the inner stent cover can be configured to release said pharmaceutical agent of the inner stent cover, wherein the outer stent cover can be configured to not release a pharmaceutical agent at all.

[0048] Thus, to summarize, only one of the inner or outer stent cover can release a pharmaceutical agent or both of them. The pharmaceutical agents of the inner and outer stent cover can be identical or different.

[0049] Particularly, in an embodiment, the outer stent cover comprises a first outer stent cover layer arranged on the scaffold and a further second outer stent cover layer arranged on top of the first outer stent cover layer, wherein said pharmaceutical agent of the outer stent cover is provided by the second outer stent cover layer, whereas the first outer stent cover layer does not contain a releasable pharmaceutical agent. Similarly, the inner stent cover can comprise a first inner stent cover layer arranged on the scaffold and a further second inner stent cover layer arranged on top of the first inner stent cover layer, wherein said pharmaceutical agent of the inner stent cover is provided by the second inner stent cover layer of the inner stent cover, whereas the first inner stent cover layer of the inner stent cover does not contain a releasable pharmaceutical agent.

[0050] According to yet another embodiment of the invention, a concentration of the pharmaceutical agent of the inner stent cover and / or an amount of the pharmaceutical agent of the inner stent cover released per time varies along a longitudinal axis of the covered stent or scaffold.

[0051] Similarly, according to a further embodiment of the invention, a concentration of the pharmaceutical agent of the outer stent cover and / or an amount of the pharmaceutical agent of the outer stent cover released per time varies along a longitudinal axis of the covered stent or scaffold.

[0052] A further aspect of the present invention relates to a method for manufacturing a covered stent, particularly a covered stent according to the present invention, wherein the method comprises:

[0053] - providing a scaffold having an inner side and an outer side,

[0054] - arranging a (tubular) inner stent cover on the inner side of the scaffold, wherein an inner surface (3 a) of the inner stent cover (3) is a microstructured surface and / or has a surface roughness Rz in the range of from 1.0 to 5.0 pm, - bonding an outer surface of the inner stent cover to the inner side of the scaffold or bonding an outer stent cover to an outer surface of the inner stent cover to enclose the scaffold between the inner stent cover and the outer stent cover, preferably in a form-fitting manner.

[0055] The inner stent cover may comprise a first polymer. The outer stent cover may comprise a second polymer. The first polymer may be bonded to the second polymer by dissolving the outer surface of the inner stent cover and an opposing (inner) surface of the outer stent cover with a solvent compatible with both the first and the second polymer. Furthermore, the opposing outer surface of the inner stent cover may be contacted with the (inner) surface of the outer stent cover to bond the outer stent cover to the inner stent cover.

[0056] The inner stent cover and the outer stent cover can comprise the same material or can consist of the same material (particularly selected from the aforementioned lists). Alternatively, the inner stent cover and the outer stent cover can comprise a different material compared to one another or can be formed from a different material compared to one another.

[0057] Arranging the tubular inner stent cover on the inner side of the scaffold may be done by spraycoating. Thus, the inner stent cover, preferably a single layer of the inner stent cover, may be spray coated on the inner side of the scaffold.

[0058] The microstructuring of the inner surface of the inner stent cover can be done by 3D-printing a (tubular) inner stent cover having a microstructured inner surface and / or having a surface roughness Rz in the range of from 1.0 to 5.0 pm surface, or by laser microstructuring / laser engraving a microstructure into (the inner) surface of the inner stent cover or by or by (hot) embossing a microstructure into (the inner) surface of the inner stent cover by using a microstructured pin tool.

[0059] The embossing of the microstructure may be done at room temperature or at elevated temperature (e.g. at 100°C) and / or by applying a pressure load (of e.g. up to 1000 N). The (hot) embossing of the microstructure using the microstructured pin tool may be done before or after arranging the (tubular) inner stent cover on the inner side of the scaffold.

[0060] The laser microstructuring / laser engraving or 3D-printing of the microstructure may be preferably done before arranging the (tubular) inner stent cover on the inner side of the scaffold. Particularly, according to an embodiment of the method, the first polymer / material of the inner stent cover and the second polymer / material of the outer stent cover can be selected as described above in conjunction with the stent according to the present invention.

[0061] The (linear, non-linear, exponential, in a polynomial fashion, logarithmical) thickness decrease of the end section(s) of the inner stent cover may be achieved by using varying amounts of a spray coating or by thickness variation during a 3D printing process or by laser ablation. The (linear, non-linear, exponential, in a polynomial fashion, logarithmical) thickness decrease of the end section(s) of the inner stent cover may be located only outside and beyond the last and outer most scaffold end in longitudinal direction, hence outside the scaffold.

[0062] Furthermore, the features described in conjunction with the stent according to the present invention can also be used to further characterize the method according to the present invention.

[0063] In the following, embodiments of the invention as well as further features and advantages shall be described with reference to the Figure, wherein

[0064] Fig. 1A shows a schematic cross-sectional and a lateral view of a covered stent as known in the prior art,

[0065] Fig. IB shows a schematic cross-sectional and a lateral view of an embodiment of a covered stent according to the present invention, wherein the covered stent comprises an inner stent cover,

[0066] Fig. 2 shows a schematic cross-sectional and a lateral view of a further embodiment of a covered stent according to the present invention, the covered stent comprising an inner stent cover and an outer stent cover,

[0067] Fig. 3 shows possible ratios of the thicknesses of the inner and outer stent cover that can apply to a covered stent according to the present invention (e.g. as shown in Fig- 2), Fig. 4 shows a schematic cross-sectional view of a further embodiment of a covered stent according to the present invention, wherein the covered stent comprises an inner stent cover and an outer stent cover, wherein the inner stent cover comprises a decreasing thickness towards an axial end of the inner stent cover,

[0068] Fig. 5A shows a macro photo of an outer stent cover of a covered stent,

[0069] Fig. 5B-C shows scanning electron microscopy images of an outer stent cover of a covered stent, and

[0070] Fig. 6 show a scanning electron microscopy image of an inner stent cover of a covered stent.

[0071] Fig. 1A shows a schematic representation of a conventional design of a covered stent 100 with an outer cover 102. Such a design can be connected to an increased risk of thrombosis due to the contact of the blood flow with the inner stent struts 101.

[0072] In contrast thereto, Fig. IB shows an embodiment of a covered stent 1 according to the present invention comprising at least an (e.g. single) inner stent cover 3 that is fluid mechanically optimized, and particularly comprises antithrombogenic properties.

[0073] Particularly, as indicated in Fig. IB, the covered stent 1 is expandable in a radial direction R from a collapsed state to an expanded state (e.g. either self-expandable or balloon-expandable), wherein the covered stent 1 comprises a scaffold 2 comprising an inner side 2a and an outer side 2b. Particularly, the tubular scaffold 2 is comprised of interconnected struts that delimit a plurality of cells of the scaffold 2, wherein the respective cell can be an open cell as shown in Fig. IB. having meandering strut structures delimiting the respective (open) cell. Further, the covered stent 1 comprises a tubular (e.g. cylindrical) inner stent cover 3 that is arranged on the inner side 2a of the scaffold 2, so that an inner surface 3 a of the inner stent cover 3 defines a lumen 4 of the covered stent 1 for the passage of blood therethrough. Particularly, the inner surface 3 a of the inner stent cover 3 is a microstructured surface and / or has a surface roughness Rz in the range of from 1.0 to 5.0 pm, so that the covered stent 1 comprises an optimized fluid mechanical behavior reducing the risk of thrombosis. An outer surface 3b of the inner stent cover 3 faces or is attached to the inner side of the scaffold.

[0074] While in the embodiment shown in Fig. IB, the covered stent 1 comprises at least one inner stent cover 3, which can be the only stent cover of the covered stent 1 so that an outside of the scaffold 2 is left uncovered, Fig. 2 shows a further embodiment of a covered stent 1 according to the present invention, wherein in addition to the features of Fig. IB the covered stent 1 also comprises an outer stent cover 5. The outer stent cover 5 has an inner surface 5a via which the outer stent cover 5 is attached to an outer surface 3b of the inner stent cover 3 and the outer stent cover has an outer surface (5b) opposite to the inner surface 5 a of the outer stent cover. The inner surface 3 a of the inner stent cover 3 defines a lumen 4 of the covered stent 1 for the passage of blood therethrough.

[0075] This allows to generate a positive connection between the scaffold 2 and the inner stent cover 3 by means of the outer stent cover 5. Particularly, the scaffold 2 itself does not need to be bonded to the inner or outer stent cover 3, 5 as it is enclosed between the inner stent cover 3 and the outer stent cover 5. Particularly, in a preferred embodiment, the properties of the polymers of the inner stent cover 3 and of the outer stent cover 5 are matched with respect to the mechanical requirements. To ensure the form-fit connection, a solvent compatible with both polymers can be used so that a connection of the inner and outer stent cover 3, 5 can be accomplished by contacting them with the solvent and bringing them in mutual contact.

[0076] The same material can be used as the material for the inner stent cover 3 and the outer stent cover 5. Alternatively, the use of different materials is also conceivable. In addition, the texture of the inner stent cover 3 and the outer stent cover 5 may be of different degrees, in that it may have fibrous or porous microstructures in addition to a smooth appearance.

[0077] Furthermore, Fig. 3 illustrates detail B of Fig. 2 according to which the inner stent cover 3 and the outer stent cover 5 can have different thicknesses t; and t0in the radial direction R of the covered stent 1 in different embodiments. Possible thickness ratios t; / t0between the inner stent cover 3 and the outer stent cover 5 are in the range from 10:1 < t;:t0< 10:1. Specific ranges are also described above.

[0078] As shown in Fig. 2, in an embodiment, the outer stent cover 5 can comprise a thickness t0that is significantly smaller than the thickness t; of the inner stent cover 3, thus allowing the outer stent cover 5 to follow the contour of the struts of the scaffold 2. The outside of the covered stent 1 thus comprises an uneven shape allowing an improved anchoring of the covered stent 1 in a vessel while the inner surface 3a of the inner stent cover 3 facing the lumen 4 can be sufficiently smooth to reduce the risk of thrombosis.

[0079] Further, Fig. 4 shows an embodiment of a covered stent 1 according to the present invention comprising a flow-optimized covered stent end 31 to provide a smooth transition between the lumen 4 of the covered stent 1 and the lumen of the vessel into which the covered stent 1 is to be implanted. Particularly, the opposing covered stent ends have been identified as particularly critical areas with respect to clinical complications. Therefore, the invention particularly also relates to particularly flow-optimized covered stent ends in certain embodiments. Such covered stent ends can be combined with all other embodiments of the present invention. Particularly, covered stent ends are conceivable in which either the scaffold 2 or the inner stent cover 3 and / or outer stent cover 5 are flow-optimized to such an extent that the connected stent covers 3, 5 form a structure that lies against the vessel wall proximally and distally to the covered stent in a flow-optimized manner.

[0080] Particularly, as indicated in Fig. 4, the inner stent cover 3 comprises a first end section 310 ending with a first end 31 of the covered stent 1, wherein a thickness t; of the inner stent cover 3 in the first end section 310 decreases along a longitudinal axis z of the scaffold 2 covered stent 1 towards said first end 31. Particularly, the first end section 310 of the inner stent cover 3 can protrude from a corresponding end of the scaffold 2 in the longitudinal direction z and can be connected to a first end section 500 of the outer stent cover 5 as well so that also the scaffold end is enclosed by the inner stent cover 3 and the outer stent cover 5. Hereby in one embodiment the first end section 310 of the inner cover and / or the first end section 500 of the outer stent cover 5 are located outside and beyond the last and outer most scaffold end in longitudinal direction. Due to the continuously decreasing thickness t; of the inner stent cover 3 in said first end section 310, the inner stent cover 3 provides a smooth transition of the covered stent lumen 4 towards the neighboring vessel wall at the end of the covered stent 1. The opposing covered stent end (not shown) can be designed in an analogous fashion. In one embodiment the decrease of thickness t; of the inner stent cover 3 in said first end section 310 is only implemented outside and beyond the last and outer most scaffold end in longitudinal direction. Hence, inside the entire length in longitudinal direction z between the outmost located scaffold struts thickness t; of the inner cover and / or the outer stent cover 5 is supposed to be constant. Furthermore, the end of the inner stent cover 3 may further be turned over outwardly. An outwardly everted inner stent cover 3 may further be thermally post-processed such that the everted inner stent cover bonds to the outer stent cover. Also, here, one can reduce the thickness of this stent cover structure at the respective end to provide a smooth transition between covered stent lumen and vessel wall. The smooth transition resulting from these measures further helps to minimize the risk of thrombosis.

[0081] Furthermore, in certain embodiments that can be combined with the embodiments described above, the covered stent 1 can also be a drug-eluting covered stent. For example, it is possible to incorporate an active agent into the outer stent cover 5, e.g., a pharmaceutical agent with antiproliferative or anti-inflammatory properties. In contrast to conventional drug-eluting covered stents, the described approach also allows the drug coating to be applied to the free spaces between the individual struts of the scaffold 2, so that the drug-eluting covered stent 1 realizes a homogeneous delivery of relatively high drug doses over the entire covered stent area to the wall surface of the blood vessel, while at the same time the inner stent cover 3 minimizes the luminal delivery of the drug, which is undesirable in conventional drug-eluting covered stents.

[0082] Furthermore, it is conceivable to incorporate the same active agent into both the outer stent cover 5 and the inner stent cover 3. Furthermore, it is conceivable to incorporate the active agent only into the inner stent cover 3. It is also conceivable to incorporate a different active agent into the inner stent cover 3 than into the outer stent cover 5, e.g., a pharmaceutical agent with antithrombogenic or endothelialization-promoting properties. The feasible combinations of active agent incorporation into the inner stent cover 3 and the outer stent covers 5 are summarized in an exemplary fashion in Table 2.

[0083] Table 2: Conceivable options for incorporation of agents A and B, or omission of incorporation of an agent (-), into the cover 3, 5 of the drug-eluting covered stent 1. Furthermore, it is ultimately also conceivable to apply an additional third or a fourth, active substance-carrying layer to the inner as well as the outer cover. Furthermore, it is possible to vary the drug content as well as the release kinetics of the drug on a longitudinal level (in z- direction) in order to control, for example, antiproliferative drug properties in a spatially and / or temporally resolved manner.

[0084] The technical feasibility of the present invention has e.g. been demonstrated by manufacturing the examples that will be described in following.

[0085] Fig. 5 A shows a macro photo (Pl) of a covered stent 1 covered with a thermoplastic silicone polycarbonate elastomer, comprising 5 wt% silicone (ChronoSil 80A), after prototyping (before crimping and dilatation).

[0086] Fig. 5B-C show scanning electron microscopy (SEM) images (SI, S2) of an outer cover of a covered stent covered with a thermoplastic silicone polycarbonate elastomer, comprising 5 wt% silicone (ChronoSil 80A) as cover material, after prototyping (before crimping and dilatation). The SEM images were obtained under 5kV high voltage at a pressure of 50 Pa. It can be seen that the outer surface of the outer stent cover comprises an uneven contour which reproduces the outer side of the scaffold. The uneven contour of the outer surface of the outer stent cover 5 comprises alternating valleys and heights, wherein the respective heights being positioned on a strut of the scaffold 2 and the respective valley between two struts. Such an uneven counter of the outer surfaces of the outer stent cover enables an anchoring of the covered stent in a vessel wall.

[0087] The covered stent can be crimped to approx. 1.8 mm and expanded to 4.0 mm, with an elastic recoil of approx. 7.9% and the cover can resist a burst pressure of > 1 bar.

[0088] Fig. 6 shows an example of a covered stent covered with a thermoplastic silicone polycarbonate elastomer, comprising 5 wt% silicone (ChronoSil 80A) condition after prototyping, crimping and dilatation to 4.0 mm. This covered stent was cut longitudinally and the inner stent cover of the covered stent was examined by scanning electron microscopy (SEM). SEM picture (S3) demonstrated that the surface of the inner stent cover is smooth, thus providing optimized fluid mechanical properties which results in a minimized risk of thrombosis. Also, a longitudinal section of a covered stent as well as a morphological analysis of the inner stent cover of the covered stent using optical coherence tomography (OCT) demonstrated that the inner stent cover is smooth. The present invention offers the advantage of a smooth inner lumen with minimized risk of thrombosis. Furthermore, individual drug-eluting functionalities of the inner and outer stent cover with optional additional longitudinal resolution are enabled. Further, the preferred use of ductile materials as described herein enables complete elimination of per- and polyfluorinated alkyl compounds (PFAs), which are present in conventional PTFE-covered stents and are currently under discussion to be harmful to health. Furthermore, the present invention can offer a significant cost reduction and allows manufacturing of a covered stent in just a few process steps.

Claims

Claims1. A covered stent (1), the covered stent (1) being expandable in a radial direction (R) from a collapsed state to an expanded state, wherein the covered stent (1) further comprises:- a scaffold (2) comprising an inner side (2a) and an outer side (2b),- a inner stent cover (3) arranged on the inner side (2a) of the scaffold (2), the inner stent cover (3) comprising an inner surface (3 a) delimiting a lumen (4) of the covered stent (1), characterized in that the inner stent cover (3) comprises a first end (31) and a first end section (310) ending with said first end (31), wherein a thickness (t;) of the inner stent cover (3) in the first end section (310) decreases along a longitudinal axis (z) of the scaffold (2) towards said first end (31 and wherein the first end section 310 of the inner cover is located outside and beyond the last and outer most scaffold end in longitudinal direction.

2. The covered stent according to claim 1, wherein the inner surface (3 a) of the inner stent cover (3) is a microstructured surface and the microstructured surface comprises more than one groove along a longitudinal direction of the covered stent, wherein each of the grooves has a depth of up to 1.0 pm and a distance between the grooves of up to 1 pm and / or a groove width of up to 1 pm.

3. The covered stent according to claim 1 or 2, wherein the covered stent (1) comprises an outer stent cover (5), wherein the outer stent cover (5) is bonded to an outer surface (3b) of the inner stent cover (3) to enclose the scaffold (2) in a form-fitting manner.

4. The covered stent according to claim 3, wherein the inner surface (3 a) of the inner stent cover (3) has a smoother cross-sectional contour in a plane perpendicular or parallel to a longitudinal axis (z) of the scaffold (2) than the outer surface (5b) of the outer stent cover (5) when the covered stent (1) is in a radially expanded state.

5. The covered stent according to claim 3 or 4, wherein an outer surface (5b) of the outer stent cover (5) comprises an uneven contour along a longitudinal axis (z) of the scaffold (2) which reproduces the outer side of the scaffold.

6. The covered stent according to one of the claims 3 to 5, wherein the inner stent cover (3) comprises a thickness t; in the radial direction (R) of the covered stent (1) and the outer stent cover (5) comprises a thickness t0in the radial direction (R) of the covered stent, wherein a thickness ratio t;:t0is in the range from 10:1 to 1:10.

7. The covered stent according to one of the preceding claims, wherein the inner stent cover (3) and / or the outer stent cover comprise or consist of a polymer, preferably from a polyurethane or silicone-based elastomer, a thermoplastic silicone polycarbonate elastomer, preferably comprising 5 wt% silicone, a polycarbonate aliphatic thermoplastic polyurethane elastomer, a thermoplastic polycarbonate polyurethane polymer, an aliphatic and aromatic polycarbonate-based thermoplastic polyurethane, a thermoplastic silicone polycarbonate polyurethane copolymer, an aromatic polyether-based thermoplastic polyurethanes, a silicone-poly urethane co-polymer or mixtures thereof.

8. The covered stent according to one of the preceding claims, wherein the scaffold has a strut thickness of 60 pm or less and wherein the thickness t; of the inner stent cover (3) in the radial direction (R) of the covered stent (1) is 30 pm or less and / or the thickness t0of the outer stent cover (5) in the radial direction (R) of the covered stent is 30 pm or less.

9. The covered stent according to one of the preceding claims, wherein the decrease of the thickness (ti) is one of: a linear decrease, a non-linear decrease, an exponential decrease, a polynomial decrease, a logarithmic decrease.

10. The covered stent according to one of the preceding claims, wherein the inner stent cover (3) and / or the outer stent cover (5) is configured to release a pharmaceutical agent.

11. The covered stent according to claim 10, wherein the pharmaceutical agent released by the outer stent cover (5) is different from the pharmaceutical agent released by the inner stent cover (3).

12. The covered stent according to claim 10 or 11, wherein the outer stent cover (5) comprises a first outer stent cover layer arranged on the scaffold (2) and a further second outer stent cover layer arranged on top of the first outer stent cover layer,wherein said pharmaceutical agent of the outer stent cover (5) is provided by the second outer stent cover layer, whereas the first outer stent cover layer does not contain a releasable pharmaceutical agent.

13. The covered stent according to any of claims 10 to 12, wherein the inner stent cover (3) comprises a first inner stent cover layer arranged on the scaffold (2) and a further second inner stent cover layer arranged on top of the first inner stent cover layer, wherein said pharmaceutical agent of the inner stent cover (3) is provided by the second inner stent cover layer of the inner stent cover, whereas the first inner stent cover layer of the inner stent cover does not contain a releasable pharmaceutical agent.

14. The covered stent according to any of claims 10 to 13, wherein a concentration of the pharmaceutical agent of the inner stent cover (3) and / or an amount of the pharmaceutical agent of the inner stent cover (3) released per time varies along a longitudinal axis (z) of the scaffold (2).

15. The covered stent according to any of claims 10 to 14, wherein a concentration of the pharmaceutical agent of the outer stent cover (5) and / or an amount of the pharmaceutical agent of the outer stent cover (5) released per time varies along a longitudinal axis (z) of the scaffold (2).

Images