Fibrillated construct for extraluminal connection

Abstract

The present invention provides a fibrillated construct adapted for minimally-invasive implantation, the fibrillated construct (100) being configured to implement extraluminal connection between different portions of a same blood vessel (V) or between different blood vessels (V), wherein the construct (100) is made of a bioresorbable material allowing for in vivo tissue formation.

Description

[0001] Fibrillated construct for extraluminal connection

[0002] The present invention belongs to the technical field of constructs, especially fibrillated constructs, for cardiovascular applications.

[0003] In particular, the invention relates to a fibrillated construct adapted for extraluminal connection between portions of a same blood vessel or different blood vessels to one another.

[0004] In the latter case, connection can be a vein-to-vein connection, an artery-to-artery connection, a vein-to-artery connection or artery-to-vein connection.

[0005] For various clinical indications, rerouting of blood flow outside of a native vessel (either an artery or vein) might be required.

[0006] For instance, this may be the case of long lesions that at least partly occlude a blood vessel (either an artery or vein), thereby requiring clinical treatment.

[0007] Occlusions can be either stenotic, where a limited blood flow through the occlusion is still possible, or total.

[0008] The stenose or occlusion can for instance be induced by progressive hyperplasia or thrombus formation or other underlying clinical conditions.

[0009] Fig. 1 shows an example of chronic total occlusion (CTO) in a blood vessel, here the tibial artery.

[0010] In this case, blood flow through the occlusion is completely inhibited.

[0011] In general, where shorter lesions more often are stenotic, longer lesions are more often associated with CTO (as shown, by way of an example, in Fig. 1).

[0012] Technical solutions exist to reopen the occluded segments, for instance with atherectomy devices.

[0013] Other options rather focus on bypassing the occluded segment to reroute the blood flow.

[0014] Rerouting of blood flow is usually accomplished by creating a bypass, a shunt, or a fistula, depending on the circumstances.

[0015] In particular, blood can be rerouted by connecting a portion of a blood vessel (e.g., an artery or vein) to another portion of the same blood vessel. Alternatively, blood can be rerouted by connecting a portion of a blood vessel to a portion of another blood vessel.

[0016] Here, connection can be either artery-to-artery, vein-to-vein, artery-to-vein, or vein-to-artery.

[0017] Artery-to-vein connections may be required in clinical applications such as hemodialysis.

[0018] In the state of the art, these connections are usually accomplished by using grafts.

[0019] Grafts can be implanted at a target site either surgically or through minimally-invasive procedures.

[0020] Grafts can be made of either synthetic or biological materials.

[0021] In both cases, grafts have the drawback that re-occlusion often occurs over time.

[0022] The occurrence of re-occlusions is prejudicial to the overall surgical outcome, often requiring further surgical interventions.

[0023] In the light of the above, it is an object of the present invention to provide a fibrillated construct for extraluminal connection, which is capable of transforming into a new biological conduit (serving either as an artery or vein), allowing for longer patency rates and reduced risk of reocclusion over time.

[0024] The invention provides a fibrillated construct adapted for minimally-invasive implantation, the fibrillated construct being configured to implement extraluminal connection between different portions of a same blood vessel or between different blood vessels, wherein the construct is made of a bioresorbable material allowing for in vivo tissue formation.

[0025] The present invention provides a fibrillated construct for extraluminal connection.

[0026] The fibrillated construct is adapted for minimally-invasive implantation.

[0027] Extraluminal connection can be created between portions of a same blood vessel.

[0028] The blood vessel can be either an artery or a vein.

[0029] Alternatively, extraluminal connection can be created between different blood vessels.

[0030] That is, blood is guided outside from a blood vessel to another portion of the same blood vessel or to a portion of a different blood vessel. When used for connection between portions of different blood vessels, the construct may be adapted to extend over a short or long distance, depending on the circumstances.

[0031] The construct is made of a bioresorbable material.

[0032] In particular, the bioresorbable material allows for in vivo tissue formation.

[0033] The construct instantly reroutes blood flow, and then gradually transforms into a new biological blood vessel as the bioresorbable material is gradually replaced by new biological tissue.

[0034] Cells from the recipient penetrate though the fibrillated structure of the construct, which facilitates tissue formation and, in turn, formation of new biological tissue.

[0035] Accordingly, a new biological conduit is formed, which merges with the existing vessel(s).

[0036] As the new biological tissue is formed, the construct degrades in the biological environment, ultimately leaving no foreign material at the implantation site (or surroundings).

[0037] The invention is based on the basic idea that, by using a fibrillated construct made of a biodegradable material capable of promoting in vivo tissue ingrowth, a new biological conduit, acting as a blood vessel (either an artery or vein) can be formed without leaving foreign material residues and with reduced risk of re-occlusion over time.

[0038] Also, the biological conduit so obtained shows longer patency rates compared to cases where grafts according to the state of the art are used.

[0039] The fibrillated construct can be minimally-invasively implanted, in particular through a transcatheter approach (e.g., using a balloon catheter or self-expansion mechanism).

[0040] Accordingly, complex and invasive surgical operations can be avoided.

[0041] Preferably, the construct is mounted to a transcatheter delivery device.

[0042] Here, the construct is advanced through an existing blood vessel (either an artery or vein), and then routed towards the outside of the true lumen for connection to another portion of the same blood vessel or a portion of a different blood vessel.

[0043] Advantageously, fibers of the construct can be arranged to form a porous mesh.

[0044] Here, cells of the recipient infiltrate into the mesh, so that voids between the fibers are filled with cells to grow new biological tissue, allowing formation of a new biological conduit. Because the construct is porous, blood cells circulate and infiltrate into the mesh.

[0045] The interaction of the immune cells with the (small) fibers forming the construct triggers a natural healing response by which host body cells start forming, and new tissue fills up voids between the fibers.

[0046] As the voids are filled up, the fibers gradually resorb over time, merely by hydrolyses.

[0047] In one configuration, the construct comprises a plurality of porous layers of different densities.

[0048] Preferably, density of each porous layer is defined to favor or inhibit cell and / or tissue infiltration and / or or tune permeability of blood.

[0049] If porosity is too large, blood can leak through the wall of the construct, which may result in internal bleedings and / or insufficient rerouting of the blood.

[0050] Accordingly, in one configuration, the construct may further comprise an outer layer made of a material which is impermeable to fluids, to prevent leaking.

[0051] The portion facing the luminal side of the construct remains more porous to facilitate cell infiltration and / or tissue growth.

[0052] Advantageously, the fibers may be arranged to promote in vivo tissue ingrowth within the porous mesh.

[0053] Porosity of the porous mesh can be tuned so as to prevent blood leakage to part of the construct.

[0054] The fibrillated construct can be made of a synthetic bioresorbable material allowing for in vivo tissue formation.

[0055] Alternatively, the fibrillated construct can be made of a biological bioresorbable material allowing for in vivo tissue formation.

[0056] Exemplary manufacturing materials for the construct may include biocompatible, bioresorbable polymeric fiber materials such as poly lactic acid (PLA) (including poly(L-lactide), poly(D- lactide), poly(D,L-lactide), polyglycolide, polycaprolactone, polydioxanone, poly(trimethylene carbonate), poly(4-hydroxybutyrate), poly(ester amides) (PEA), polyurethanes, poly(trimethylene carbonate), poly(ethylene glycol), poly(vinyl alcohol), polyvinylpyrrolidone, polyhydroxyalkanoate, polyfumuarate, and copolymers thereof. Alternatively, manufacturing materials for the construct may include biological components, such as hyaluronan, collagen, gelatin, chitosan, alginate, aloe / pectin, cellulose or other biological materials originating from tissues from either autologous, allergenic or xenogenic origin), or a combination thereof.

[0057] In one configuration, the construct is expandable.

[0058] In one configuration, the construct has a tubular shape.

[0059] In particular, in one configuration, the construct is an expandable tubular construct having a first diameter prior to expansion, and a second diameter after expansion, the second diameter being larger than the first diameter.

[0060] Because the diameter of the construct is smaller prior to implantation, the construct can be easily implanted and guided to the target site within the patient’s body.

[0061] Then, once deployed at the implantation site, the construct is expanded to a larger diameter, preventing undesired displacement.

[0062] Preferably, the first diameter is between 0.5 mm and 10 mm.

[0063] Preferably, the second diameter is between 2 mm and 45 mm.

[0064] An optimal diameter for the construct shall be defined on a case-by-case basis, depending on the specific surgical application and / or the patient’s anatomy.

[0065] Usually, smaller diameters are used for smaller vessel indications, where the construct also needs to be expanded to a limited diameter.

[0066] On the other hand, larger blood vessels usually require larger diameters especially because, in these cases, the construct needs to expand to a larger diameter after implantation.

[0067] The first diameter prior to implantation is often referred to with French sizes, where 1 French equals 1 / 3 mm, to reflect catheter compatibility.

[0068] For coronary, below-the-knee or AV fistula applications, constructs normally have 4-6 French, sometimes 7-8 French compatibility for implantation.

[0069] Constructs for these indications need to expand to 2.5, 3 or sometimes even 4 to 5 mm in diameter for arterial applications or even larger beyond 5 to 8-10 mm for proper vein apposition.

[0070] In one configuration, the tubular construct may have a length between 10 mm up to 400 mm. Similar as above, an optimal length for the construct shall be defined based on the specific surgical application and / or the patient’s anatomy.

[0071] In another configuration, the construct may have a non-uniform tubular shape having at least two different diameters.

[0072] For instance, the construct may have a non-uniform tubular body with different, i.e. enlarged or reduced, diameters at its proximal and distal ends.

[0073] Additionally or alternatively, the construct may include a non-uniform tubular body having different diameters along its length.

[0074] They could be concave or convex shaped.

[0075] In yet another configuration, the construct may have a non-uniform tubular shape including bends or twists.

[0076] Here, the construct can be pre-shaped to include bends or twists.

[0077] The construct does not necessarily need to have full wall apposition.

[0078] In one example, when making an artery-to-vein connection, the construct can have good wall apposition in the artery, but intentionally not have full apposition in the vein, so as not to occlude the native blood flow through the vein.

[0079] In a still further configuration, the construct may be in the shape of a graft.

[0080] The construct may be configured and adapted to create an artery-to-artery extraluminal connection.

[0081] Alternatively, the construct may be configured and adapted to create a vein-to-vein extraluminal connection.

[0082] As a further alternative, the construct may be configured and adapted to create a vein-to-artery or artery-to-vein extraluminal connection.

[0083] Multiple separate constructs can be used in a target blood vessel to create the connection.

[0084] As an example, only the inflow and outflow connection can be made, without the need to have the two parts connected by the same construct. Further details and advantages of the invention will now be disclosed in connection with the drawings, where:

[0085] Fig. 1 is a diagram showing an occlusion, in particular a chronic total occlusion (CTO), in a blood vessel, here the tibial artery;

[0086] Fig. 2 is a diagram showing an exemplary in vivo application according to the prior art, where a tubular device is inserted inside the lumen of a blood vessel (here the tibial artery) through an occlusion, to restore blood flow within the lumen;

[0087] Fig. 3 is a diagram showing an exemplary in vivo application, where the fibrillated construct of the invention is inserted and routed inside the sub-intimal space of a blood vessel (here, the tibial artery);

[0088] Fig. 4 is a diagram showing another exemplary in vivo application, where the fibrillated construct of the invention is routed outside the lumen of a blood vessel, guided outside of the vessel, and then advanced back into the lumen;

[0089] Fig. 5 is a diagram showing a different view of the exemplary in vivo application shown in Fig. 3;

[0090] Fig. 6 is a diagram showing another exemplary in vivo application, where the fibrillated construct of the invention is routed outside the lumen of a blood vessel, guided outside of the blood vessel, and then advanced into the lumen of another blood vessel;

[0091] Fig. 7 is a diagram showing yet another exemplary in vivo application, where the fibrillated construct of the invention is used to create an endovascular fistula, e.g. connecting an artery to a vein;

[0092] Fig. 8 is a diagram similar to that of Fig. 7, where the fibrillated construct of the invention is especially used to create an endovascular fistula connecting the tibial artery to the tibial vein to bypass an occlusion, in particular a chronic total occlusion (CTO);

[0093] Figs. 9a-b are images illustrating an exemplary implantation of the fibrillated construct of the invention in a laboratory experiment carried out on a cadaver. The construct is used to create an endovascular arteriovenous fistula (endoAVF) in the arm; Fig. 10a-c are diagrams showing an exemplary in vivo application of the fibrillated construct of the invention in hemodialysis, in particular for generating an endovascular arteriovenous fistula (endoAVF) in the arm of a patient.

[0094] Fig. 2 shows an exemplary in vivo application according to the prior art, where a tubular device is inserted into the lumen of a blood vessel, after a proper surgical preparation.

[0095] Surgical preparation may be carried out through standard surgical techniques, such as atherectomy devices, (high pressure) balloons, or lithotripsy.

[0096] The construct extends through the occlusion, so that blood flow within the vessel (in the shown example, the tibial artery) can be restored.

[0097] Figs. 3-8 show different in vivo applications of a fibrillated construct 100 according to the invention.

[0098] The construct 100 is adapted for minimally-invasive implantation.

[0099] In the present embodiment, the fibrillated construct 100 has a tubular shape.

[0100] In particular, in the present embodiment, the construct 100 is a tubular construct 100 having a first diameter prior to expansion and a second diameter after expansion, the second diameter being larger than the first diameter.

[0101] In particular, in the present embodiment, the first diameter is between 0.5 mm and 10 mm, while the second diameter is between 2 mm and 45 mm.

[0102] An optimal diameter for the construct 100 shall be defined on a case-by-case basis, depending on the specific surgical application and / or the patient’s anatomy.

[0103] Also, in the present embodiment, the construct 100 has a length between 10 mm and 400 mm.

[0104] Similar as above, an optimal length for the construct 100 shall be defined based on the specific surgical application and / or the patient’s anatomy.

[0105] Not shown is that, alternatively, the construct may have a non-uniform tubular shape having at least two different diameters.

[0106] Not shown is that, alternatively, the construct may have a non-uniform tubular shape including bends or twists.

[0107] Also not shown is that, alternatively, the construct may be in the shape of a graft.

[0108] The fibrillated construct 100 is adapted for extraluminal connection between different portions of a same blood vessel V or between different blood vessels V. The construct 100 is made of a bioresorbable material allowing for in vivo tissue formation.

[0109] In the present embodiment, fibers forming the construct 100 are arranged to form a porous mesh.

[0110] Conveniently, the fibers are arranged to promote in vivo tissue ingrowth within the porous mesh.

[0111] Advantageously, porosity of the porous mesh is defined so as to prevent blood leakage to part of the construct 100.

[0112] After implantation, cells of the recipient infiltrate through the porous mesh, so that natural tissue is allowed to grow within the voids between the fibers.

[0113] Accordingly, a new biological conduit is formed, which merges with the existing vessel(s) V.

[0114] After formation of the biological conduit, the fibrous construct resorbs in the biological environment, without leaving foreign material.

[0115] In the present embodiment, the construct 100 is made of a synthetic bioresorbable material, allowing for in vivo tissue formation.

[0116] Alternatively, the construct 100 can be made of a biological bioresorbable material, allowing for in vivo tissue formation.

[0117] Exemplary manufacturing materials for the construct 100 may include biocompatible, bioresorbable polymeric fiber materials such as poly lactic acid (PLA) (including poly(L-lactide), poly(D-lactide), poly(D,L-lactide), polyglycolide, polycaprolactone, polydioxanone, poly(trimethylene carbonate), poly(4-hydroxybutyrate), poly(ester amides) (PEA), polyurethanes, poly(trimethylene carbonate), poly(ethylene glycol), poly(vinyl alcohol), polyvinylpyrrolidone, polyhydroxyalkanoate, polyfumuarate, and copolymers thereof.

[0118] Alternatively, manufacturing materials for the construct 100 may include biological components, such as hyaluronan, collagen, gelatin, chitosan, alginate, aloe / pectin, cellulose or other biological materials originating from tissues from either autologous, allergenic or xenogenic origin), or a combination thereof.

[0119] Advantageously, in the present embodiment, the construct 100 may comprise a plurality of porous layers of different densities.

[0120] Preferably, density of each porous layer is defined to favor or inhibit cell and / or tissue infiltration and / or tune permeability of blood.

[0121] Not shown is that the construct 100 may further comprise an outer layer made of a material which is impermeable to fluids. Advantageously, in the present embodiment, the fibrillated construct 100 is expandable.

[0122] The construct 100 can be configured and adapted to create an artery-to-artery extraluminal connection.

[0123] Alternatively, the construct 100 can be configured and adapted to create a vein-to-vein extraluminal connection.

[0124] As a further alternative, the construct 100 can be configured and adapted to create a vein-to- artery or artery-to-vein extraluminal connection.

[0125] Fig. 3 shows an exemplary in vivo application where the construct 100 is inserted into the sub- intimal space S of the blood vessel V (in the shown example, the tibial artery).

[0126] In particular, the construct 100 is routed outside the lumen L of the blood vessel V into the sub- intimal space S of the vessel wall W, and guided through the vessel wall W.

[0127] Then, the construct 100 is advanced back into the lumen L of the same blood vessel V through re-entry of the intima, bypassing the occlusion.

[0128] This application can be implemented by using dedicated crossing devices, or with (special) guide wires.

[0129] A different schematic illustration of this exemplary in vivo application is provided in Fig. 5.

[0130] Fig. 4 shows another exemplary in vivo application, where the tubular construct 100 is routed outside the lumen L of a blood vessel V (either an artery or vein) through the lumen wall W, and is guided outside of the blood vessel V.

[0131] Then, the construct 100 is advanced back into the lumen L of the same blood vessel V through the wall W.

[0132] The construct 100 can also be used to create a connection between two blood vessels V.

[0133] Fig. 6 shows an exemplary in vivo application where the tubular construct 100 is routed outside the lumen L of a blood vessel V through the wall W, and guided outside of the blood vessel V.

[0134] Then, the construct 100 is advanced into another blood vessel V.

[0135] For example, the construct 100 can be routed from an occluded artery into a vein to bypass an occlusion O, without being subsequently rerouted into the artery.

[0136] This approach is known as deep-vein arterialization.

[0137] In particular, by making this connection, the original vein becomes a new artery, while the construct 100 defines a new biological conduit. Fig. 7 shows yet another an exemplary in vivo application where the tubular construct 100 is used to create a fistula.

[0138] Here, the construct 100 is routed outside the lumen L of a blood vessel V through the wall W, and guided outside of the blood vessel V.

[0139] Then, the construct 100 is advanced into another blood vessel W.

[0140] Subsequently, after being advanced into the other blood vessel V, the construct 100 is guided back into the initial blood vessel V.

[0141] In this case, the second blood vessel V serves as a channel in which the construct 100 is placed.

[0142] Fig. 8 illustrates an example where the construct 100 is used to create a fistula connecting an occluded artery to a vein.

[0143] In the shown example, the artery is the tibial artery, and the vein is the tibial vein.

[0144] Here, the construct 100 is inserted into the artery above the occlusion O, routed outside the artery and guided into the vein, and then rerouted into the artery, bypassing the occlusion O.

[0145] By way of an example, re-entry into the artery can be accomplished through guide wire techniques or dedicated re-crossing devices.

[0146] This can be for example used to treat CLTI. Chronic limb-threatening ischemia (CLTI) is a serious condition caused by severe blockages in the arteries of the legs or feet, leading to insufficient blood flow and oxygen. It's essentially an advanced stage of peripheral artery disease (PAD) and can result in severe pain, ulcers, and even amputation. CLTI is also associated with a higher risk of stroke or heart attack. By providing such a bypass, sufficient blood flow to the lower limbs can be re-established to facilitate wound healing and prevent amputation.

[0147] The construct 100 of the invention is adapted for use, e.g., in the following cardiovascular applications: bypass indications such as: bypasses in the coronary domain; bypasses in the peripheral vasculature; bypasses in the neurovascular space. arteriovenous (AV) access, either for fistula, shunts or grafts.

[0148] As mentioned, the construct 100 can be minimally-invasively delivered to a target site (e.g., through a delivery system), or can be surgically implanted.

[0149] For example, the construct can be deployed at a target side by using a balloon catheter. Figs. 9a-b show an exemplary implantation of the fibrillated construct 100 in the context of a laboratory experiment carried out on a cadaver, where the construct 100 was used to create an endovascular arteriovenous fistula (endoAVF) connecting an artery to a vein.

[0150] In this experiment, the fistula was created in the arm.

[0151] The construct 100 was advanced over a wire to establish the artery-to-vein connection.

[0152] This laboratory experiment, relying on a fully-endovascular approach, revealed promising results.

[0153] In particular, undesired kinking after implantation could be prevented.

[0154] Also, the construct 100 allows achieving a smooth artery-to-vein transition.

[0155] The construct 100 can be used in hemodialysis, in particular for endovascular arteriovenous fistula (endoAVF) indications, to create a new blood vessel between an artery and a vein.

[0156] An exemplary in vivo application where the fibrillated construct of the invention is used in hemodialysis is illustrated in Figs. 10a-c.

[0157] Here, an endovascular arteriovenous fistula (endoAVF) is created (e.g. in the arm of a patient, as shown in Fig. 10a), connecting an artery to a vein (Figs. 10b-c).

[0158] Hemodialysis is a process of filtering blood of a patient, especially affected by kidney failure, for extracorporeal removal of waste products (e.g. creatinine, urea, or the like) from the patient’s blood.

[0159] Hemodialysis is carried out by using a dialysis machine (also known as dialyser), comprising a plurality of membranes serving as filters to remove waste products from the blood, which are passed into a dialysate fluid.

[0160] By generating a fistula, the vein mature, growing made larger and stronger, thus facilitating transfer of blood from the patient’s body to the dialysis machine, and subsequently back to the body.

[0161] A pair of thin needles is inserted into the fistula. In particular, a first thin needle is used to slowly remove blood to be filtered from the fistula and transfer it to the dialysis machine, while the other thin needle is used to transfer filtered blood from the dialysis machine back into the fistula (Fig. 10b). In this application, the vein and artery are bit further spanned, and the construct 100 needs to cross the space between the artery and the vein, before getting back into the vein.

[0162] Here, the intention is to grow a new biological conduit between the artery and the vein to keep the connection longer open, to stimulate proper maturation of the vein for hemodialysis. The construct 100 transforms into a new biological conduit to secure patency and blood supply to the vein.

[0163] According to an alternative approach (not shown), the construct 100 can be used as a puncture side to facilitate hemodialysis access, serving as implant or as newly-formed biological conduit.

[0164] Also, for peripheral indications, the construct 100 can be used to create and endovascular bypass for SFA, Popliteal, or below-the-knee indications, mainly to bypass occlusions, in particular total occlusions.

[0165] Still further, the construct 100 can be used in the peripheral space to connect an artery and a vein to restore blood flow in a foot, e.g. for deep vein arterial ization indications.

[0166] References

[0167] 100 Fibrillated construct

[0168] V Vessel (vein, artery)

[0169] L Lumen

[0170] W Wall

[0171] S Sub-intimal space

[0172] O Obstruction

Claims

Claims1. A fibrillated construct (100) adapted for minimally-invasive implantation, the fibrillated construct (100) being configured to implement extraluminal connection between different portions of a same blood vessel (V) or between different blood vessels (V), wherein the construct (100) is made of a bioresorbable material allowing for in vivo tissue formation.

2. The construct (100) of claim 1 , characterized in that fibers forming the construct (100) are arranged to form a porous mesh.

3. The construct (100) of claim 2, characterized in that the fibers are arranged to promote in vivo tissue ingrowth within the porous mesh.

4. The construct (100) claim 2 or 3, characterized in that the construct (100) comprises a plurality of porous layers having different densities, preferably wherein density of each porous layer is defined to favor or inhibit cell and / or tissue infiltration and / or tune permeability of blood.

5. The construct (100) of any of claims 2 to 4, characterized in thatthe construct (100) further comprises an outer layer made of a material which is impermeable to fluid.

6. The construct (100) of any of claims 2 to 5, characterized in that porosity of the porous mesh is defined so as to prevent blood leakage to part of the construct (100).

7. The construct (100) of any of the preceding claims, characterized in that the construct (100) is made of a synthetic bioresorbable material allowing for in vivo tissue formation.

8. The construct (100) of claims 1 to 6, characterized in that the construct (100) is made of a biological bioresorbable material allowing for in vivo tissue formation.

9. The construct (100) of any of the preceding claims, characterized in that the construct (100) is expandable.

10. The construct (100) of any of the preceding claims, characterized in thatthe construct (100) has a tubular shape.

11. The construct (100) of claim 10, characterized in that the construct (100) is an expandable tubular construct (100) having a first diameter prior to expansion and a second diameter after expansion, the second diameter being larger than the first diameter, wherein the first diameter is between 0.5 mm and 10 mm, and the second diameter is between 2 mm and 45 mm.

12. The construct (100) of claim 10 or 11 , characterized in that the construct (100) has a length between 10 mm and 400 mm.

13. The construct (100) of any of claims 1 to 9, characterized in that the construct (100) has a non-uniform tubular shape having at least two different diameters, or the construct (100) has a non-uniform tubular shape including bends or twists, or the construct (100) is in the shape of a graft.

14. The construct (100) of any of the preceding claims, characterized in that the construct (100) is configured and adapted to create an artery-to-artery or vein-to- vein extraluminal connection.

15. The construct (100) of any of claims 1 to 13, characterized in that the construct (100) is configured and adapted to create a vein-to-artery or artery-to- vein extraluminal connection.

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