Biomimetic implantable vascular graft and process for its manufacturing

Abstract

The present invention concerns in general a process (100) for manufacturing an implantable vascular graft (10) with a hollow tubular structure having an internal lumen shape, the process comprising the steps consisting of providing (110) a collector (50) with a predominantly elongated development along a collector axis, made of at least partially conductive material, having an external shape substantially corresponding to the internal lumen shape; placing (120) the collector (50) in rotation around a rotation axis (A) coincident with the collector axis; dispensing and accelerating by electrospinning (130) at least a plurality of nanofibres, at least part of which is made of medical grade thermoplastic polyurethane, in the direction of the collector (50) placed in rotation, to form at least a sleeve of nanofibres around the collector (50); heat-treating (140) the at least one nanofibre sleeve for an interval of time sufficient to bring it to a temperature close to or substantially equal to a glass transition temperature of the thermoplastic polyurethane in which the at least part of the plurality of nanofibres is made, thereby resulting in a structure of at least partially crystallized nanofibres that make up the implantable vascular graft (10); and separating (150) the implantable vascular graft (10) thus obtained from the collector (50).

Description

[0001] BIOMIMETIC IMPLANTABLE VASCULAR GRAFT AND PROCESS FOR ITS MANUFACTURING

[0002] TECHNICAL FIELD

[0003] The present invention concerns in particular a process for manufacturing an implantable vascular graft capable of manufacturing vascular grafts that not only have excellent perforating and biocompatibility characteristics, but which are also biomimetic and can be produced with dimensions suitable for replacing capillary, peripheral or cerebral vessels. The present invention also concerns implantable perforatable, biocompatible and biomimetic grafts.

[0004] BACKGROUND

[0005] Several types of grafts have been described in the literature that have tried to offer solutions to the problem of reducing fluid leak from the perforation sites after removal of the perforating object, typically a needle. The most common graft materials that allow repeated perforation are polyethylene terephthalate (PET) and expanded polytetrafluoroethylene (ePTFE). In order to reduce the leaks downstream of a perforation, it is also known to make use of laminated materials comprising the above-mentioned materials and a layer of self-sealing material, such as an implantable elastomeric material. These elastomeric materials are typically silicone, polyurethane or fluoroelastomers.

[0006] Generally, use is made of a layer of elastomeric material covered on both surfaces (e.g. inner and outer surface) by a layer of graft material. The layers of graft material may comprise on the two surfaces the same or different materials and / or differ in thickness, bulk density, porosity, orientation or other characteristics, even when they have substantially the same chemical composition. In addition, the layer covering the inner surface can be medicated, i.e. impregnated with at least one active substance in order to achieve specific therapeutic effects.

[0007] In particular, for vascular grafts, it is known to start with an elastomeric material element produced in the form of a tube that is previously everted (i.e. turned inwards) and then laminated with one or more layers of graft material. The eversion results in a condition of circumferential precompression on its luminal surface (inner surface), while the abluminal surface (outer surface) is subjected to circumferential tension.

[0008] This production technique is not, however, capable of obtaining vascular grafts with dimensions sufficiently small in terms of internal lumen and structure thickness to be suitable for replacing capillary, peripheral or cerebral blood vessels. Moreover, the use of a tube made of elastomeric material makes the graft hermetic and therefore unable to transfer gases and metabolites to the external tissues, a function that a capillary vessel must be able to perform.

[0009] Moreover, the known production techniques are not suitable for manufacturing implantable vascular grafts that can be easily sutured, have elastic properties capable of facilitating re-closure in the event of a syringe needle puncture or laceration, and are at the same time biomimetic.

[0010] In the context of this description and in the appended claims, “biomimetic” is intended to mean a material capable of emulating and reproducing at least part of the phenomena observed in biological processes such as, for example, nesting and subsequent long-term cell growth when implanted within a living host organism.

[0011] OBJECTS AND SUMMARY OF THE INVENTION

[0012] In light of the above, the problem underlying the present invention is to devise a process for manufacturing an implantable vascular graft with a tubular structure that allows manufacturing vascular grafts with dimensions suitable for the replacement of capillary, peripheral or cerebral blood vessels.

[0013] In the context of this problem, an object of the present invention is to devise a process for manufacturing an implantable vascular graft capable of obtaining tubular structure grafts whose dimension of the internal lumen and / or of the structure thickness is smaller than the respective dimensions of state-of-the-art vascular grafts.

[0014] Another object of the present invention is to realise a process for manufacturing an implantable vascular graft that is capable of obtaining vascular grafts that are able to transfer gases and metabolites towards external tissues.

[0015] A further object of the present invention is to realise a process for manufacturing an implantable vascular graft capable of obtaining vascular grafts that, in addition to high perforating and biocompatibility characteristics, are biomimetic.

[0016] Last but not least, the object of the present invention is to manufacture an implantable vascular graft with a tubular structure that can be easily sutured, has elastic properties capable of facilitating re-closure in the event of a syringe needle puncture or laceration, and is at the same time biomimetic.

[0017] In accordance with a first aspect thereof, the invention thus concerns a process for manufacturing an implantable vascular graft with a tubular structure having an internal lumen shape, the process comprising the steps consisting of:

[0018] - providing a collector with a predominantly elongated development along a collector axis, made of at least partially conductive material, having an external shape substantially corresponding to the internal lumen shape;

[0019] - placing the collector in rotation around a rotation axis coincident with the collector axis;

[0020] - dispensing and accelerating by electrospinning at least a plurality of nanofibres, at least part of which is made of medical grade thermoplastic polyurethane, in the direction of the collector placed in rotation, to form at least a sleeve of nanofibres around the collector;

[0021] - heat-treating the at least one nanofibre sleeve for an interval of time sufficient to bring it to a temperature close to or substantially equal to a glass transition temperature of the medical grade thermoplastic polyurethane in which the at least part of the plurality of nanofibres is made, thereby resulting in a tubular structure of at least partially crystallized nanofibres that make up the implantable vascular graft; and

[0022] - separating the implantable vascular graft thus obtained from the collector.

[0023] In the context of this description and in the appended claims, “medical grade” is intended to mean a material that meets the requirements of at least one national or international regulation governing the biocompatibility of the materials for use thereof in medical devices, such as EU Regulation 2017 / 745 (MDR) or ISO 10993 norm or FDA regulations or USP Class VI standard.

[0024] The Applicant has identified that with the process according to the invention, it becomes possible to manufacture implantable vascular grafts starting from 20 pm of structure thickness and 200 pm of internal lumen, which are biomimetic and have elastic properties that facilitate re-closure in the event of a syringe needle puncture or laceration, which can thus be easily sutured.

[0025] In accordance with a second aspect thereof, the invention concerns an implantable vascular graft comprising a hollow tubular structure having at least one tubular structure thickness t, wherein the hollow tubular structure is made of at least one polyurethane and incorporates within its own structure thickness a plurality of irregular cavities with dimensions varying between 2 pm and 100 pm, preferably between 2 pm and 90 pm, more preferably between 2 pm and 80 pm, wherein the irregular cavities are distributed throughout the at least one structure thickness.

[0026] Advantageously, the implantable vascular graft thus configured allows to achieve the same advantages as described with reference to the process for manufacturing an implantable vascular graft according to the invention.

[0027] Further features of the preferred embodiments of the process for manufacturing an implantable vascular graft and the implantable vascular graft according to the present invention are the subject-matter of the dependent claims.

[0028] The different features in the individual configurations may be combined with one another as desired according to the preceding description, should there be advantages specifically resulting from a specific combination.

[0029] BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Further characteristics and advantages of the present invention will become clearer from the following detailed description of some preferred embodiments thereof, made with reference to the appended drawings.

[0031] In such drawings, figure 1 is a block diagram of a preferred embodiment of the process for manufacturing an implantable vascular graft according to the present invention; figure 2 is a schematic representation of an implant suitable for implementing the process of figure 1 ; figure 3 is a partial cross-section of an implantable vascular graft obtained through the process of figure 1; figure 3a is a partial cross-section of a state-of-the-art implantable vascular graft; figure 4 is a partial longitudinal section of an implantable vascular graft obtained through the process of figure 1; and figure 5 is a microscopic image of an implantable vascular graft obtained through the process of figure 1 after 7 days of in-vitro culture with MSC cells.

[0032] DETAILED DESCRIPTION OF THE INVENTION

[0033] For the illustration of the drawings, use is made in the following description of identical numerals or symbols to indicate construction elements with the same function. Moreover, for clarity of illustration, certain references may not be repeated in all drawings.

[0034] While the invention is susceptible to various modifications and alternative constructions, certain preferred embodiments are shown in the drawings and are described hereinbelow in detail. It must in any case be understood that there is no intention to limit the invention to the specific embodiment illustrated, but, on the contrary, the invention intends covering all the modifications, alternative and equivalent constructions that fall within the scope of the invention as defined in the claims.

[0035] The use of “for example”, “etc ”, “or” indicates non-exclusive alternatives without limitation, unless otherwise indicated. The use of “comprises” and “includes” means “comprises or includes, but not limited to”, unless otherwise indicated.

[0036] With reference to figure 1, there is illustrated a preferred embodiment of a process for manufacturing an implantable vascular graft 10 according to the present invention, overall indicated with 100. The implantable vascular graft 10 that can be manufactured starting from the process according to the invention has a hollow tubular structure, with an internal lumen having a shape with a predominantly elongated development along a longitudinal development axis B of the vascular graft 10 which, depending on the embodiment, may have a diameter d and / or a structure thickness t that are substantially constant or variable along the development axis B, both measured in a section transverse to said longitudinal development axis B.

[0037] In a preferred embodiment, the implantable vascular graft 10 that can be manufactured starting from the process according to the invention has a hollow tubular structure with a cylindrical internal lumen, i.e. having a diameter d substantially constant along the longitudinal development axis B.

[0038] RECTIFIED SHEET (RULE 91 ) ISA / EP The process comprises a first step 110 in which a collector 50 with a predominantly elongated development along a collector axis, made of at least partially conductive material, such as for example metallic material, is provided. The collector 50 has an external shape that substantially defines the shape of the internal lumen of the implantable vascular graft 10.

[0039] In particular, the collector 50 may be cylindrical, with a preferably circular cross -section having a diameter de substantially corresponding to the diameter d of the internal lumen that characterises the vascular graft 10 with a cylindrical internal lumen to be manufactured. In particular, the collector 50 has a cylinder diameter dccomprised between 200 pm and 10.00 mm, preferably comprised between 250 pm and 8.00 mm, more preferably comprised between 300 pm and 5.50 mm, such as for example comprised between 200 pm and 4.00 mm, or comprised between 250 pm and 3.00 mm, or even comprised between 300 pm and 2.50 mm.

[0040] In alternative embodiments, not illustrated, the collector may be conical or, in general terms, may have a shape suitable for reproducing a geometry of an internal lumen of a vessel to be replaced.

[0041] The collector 50 is preferably made of or plated with a stainless and / or sterilisable material, such as for example stainless steel and / or titanium. In addition, the collector 50 is preferably made of or plated with a material having a low roughness, such as for example a roughness characterised by surface protrusions having dimensions lower than 1 pm, preferably lower than 0.7 pm, such as for example protrusions having dimensions lower than 0.2 pm.

[0042] In the context of this description and in the appended claims, “dimensions of a surface protrusions” is intended to indicate the diameter of the smallest hemisphere which, developing from the surface, encloses the surface protrusion.

[0043] In a subsequent step (step 120), the collector 50 is placed in rotation around a rotation axis A corresponding to its own collector axis. The collector 50 is placed in rotation at an initially low speed, such as for example a speed less than or equal to 200 rpm.

[0044] Then, an electrospinning step (step 130) of a set of nanofibres takes place, of which at least one type is in polyurethane (PU) of the biocompatible type, i.e. medical grade thermoplastic polyurethane. By way of example, polyurethanes of the biocompatible type or medical grade thermoplastic polyurethanes available on the market are Elastollan® TPU produced by the company BASF or Carbothane™ TPU produced by the company Lubrizol.

[0045] As part of the electrospinning step, at least one nanofibre precursor solution is accelerated by an electric field in the direction of the collector 50 placed in rotation. This creates nanofibres that will deposit on the collector, forming a tubular structure or sleeve (not illustrated) around the collector 50.

[0046] The electrospinning step 130 takes place by applying a voltage comprised between 5 kV and 40 kV to a plurality of emitting needles and by dispensing one or more nanofibre precursor solutions with a flow rate comprised between 0.1 ml / h and 50 ml / h per needle. The voltage applied to the individual needles of the plurality of emitting needles, as well as the flow rate set and the material processed, may differ from needle to needle within the indicated intervals.

[0047] The speed at which the collector 50 is placed in rotation can reach even 6,000 rpm. Depending on the rotational speed of the collector 50, the resulting sleeve has a predominantly random or predominantly circumferentially aligned nanofibre distribution. Still, the rotational speed of the collector 50 influences the porosity of the resulting tubular structure. In particular, the higher the rotational speed, the more aligned the nanofibres will be and the smaller the dimensions of the pores or cavities of the structure. The rotational speed of the collector 50 is also chosen based on the diameter of the collector 50 itself and the thickness of the sleeve to be made.

[0048] The nanofibre sleeve is then subjected to a heat-treatment step (step 140), which comprises heating the sleeve for an interval of time sufficient to bring it to a temperature close to or substantially equal to a glass transition temperature of the thermoplastic polyurethane in which at least part of the nanofibres that make up the sleeve is manufactured. By way of example, the sleeve can be placed in an oven preheated to at least 180 °C for a time varying between 2 s and 5 min as a function of the diameter of the sleeve.

[0049] This generates a crystalline tubular structure of the polyurethane in which the thermoplastic polyurethane nanofibres partially weld together. This tubular crystalline structure forms the implantable vascular graft 10.

[0050] In the final step (step 150) of the process for manufacturing an implantable vascular graft 10, the sleeve thus created is separated from the collector 50 also by resorting, if necessary, to dismounting and / or destroying one or more components that make up the collector 50. Preferably, the sleeve separated from the collector 50 is then packed and sterilised.

[0051] FIRST EXAMPLE ACCORDING TO THE INVENTION

[0052] The following describes the instrumentation and process parameters used in an exemplary implementation of the process 100 according to the present invention, which made it possible to manufacture an implantable vascular graft 10 with a length comprised between 60 mm and 90 mm, an internal lumen having a diameter d equal to about 0.8 mm and a structure thickness t of less than 100 pm.

[0053] The following components were used for the electrospinning step 130:

[0054] • 10 ml glass syringe

[0055] • Needle gauge G21

[0056] • Rotating cylindrical collector: diameter 0.8 mm, length 90 mm

[0057] The first steps of the process (steps 110-130) were carried out with the following process parameters:

[0058] • Flow rate: 1-3 ml / h

[0059] • Tension: 30 kV

[0060] • Needle / collector distance: 90 mm

[0061] • Collector rotational speed: 50 rpm

[0062] • Translational speed: 50 mm / s

[0063] • Electrospinning time: 900 s

[0064] The heating step 140 was carried out with the following process parameters:

[0065] • Heating temperature: 200 °C

[0066] • Heating time: 20-40 s in preheated oven

[0067] The vascular graft 10 thus obtained has elasticity and mechanical properties, such as mechanical tensile strength and elongation at break, that are comparable or higher than the mechanical and elasticity properties that characterise the blood vessels to which it is to be sutured, thus favouring surgical grafting and suturing operations.

[0068] Moreover, the vascular graft 10 thus obtained has its own thickness t of structure, shown in exemplary terms in figure 3, which comprises a plurality of irregular cavities (pores) that are at least partially interconnected one another, so as to allow a minimum passage of fluids between the inside and the outside of the graft, in analogy to the physiological behaviour of the capillary vessels.

[0069] In essence, the vascular graft 10 consists of a porous membrane that prevents the crossing by particles with dimensions larger than 800 nm, preferably larger than 400 nm, more preferably larger than 100 nm, but allows the passage of smaller particles from the inside to the outside and vice versa, such as for example particles of nutrients, metabolites, carbon dioxide and oxygen.

[0070] In any case, although the porosity is high, the vascular graft 10 is suitable for substantially retaining a fluid flowing within it, without substantial leaks. This effect is due to the ability of the graft membrane to retain particles with the dimensions indicated above, i.e. to the high loss of flow rate due to the small pore dimensions and the tortuous path the fluid undergoes to cross its thickness.

[0071] As can be noted from the image shown in figure 3, the cavities are distributed along the entire thickness t of the structure of the vascular graft 10 according to the present invention, differing from a typical structure of the vascular grafts 60 of the state of the art, shown in figure 3 a relating to the GORE® ACUSEAL product (image taken from the website which comprise at least one elastomer layer 61 that is completely devoid of cavities.

[0072] Figure 4 shows a portion of the inner wall of the vascular graft 10 thus obtained. The image reported in figure 4 shows the cavities present on the inner wall of the vascular graft 10 according to the present invention in which cells can nest, adhere and proliferate. Given the presence of cavities along the entire thickness t of this vascular graft 10, similar cavities are also present on the outer wall of the graft 10.

[0073] Such a porous structure makes the vascular graft 10 thus obtained biomimetic, allowing groups of cells to nestle in the pores and live inside, as is visible from figure 5, which shows a vascular graft 10 manufactured through the process according to the present invention downstream of a 7- day in vitro culture with MSC cells (mesenchymal stem cells). The light-coloured dots represent the living cells, fixed on the surface of the graft (black part).

[0074] Advantageously, by appropriately choosing the electrospinning time, it is possible to manufacture implantable vascular grafts 10 according to the present invention with a structure thickness t comprised between 20 pm and 500 pm, preferably between 20 pm and 300 pm, more preferably between 20 pm and 80 pm.

[0075] Furthermore, in the case of cylindrical collector 50, by appropriately selecting the diameter dc, it is possible to manufacture implantable vascular grafts 10 according to the present invention with an internal lumen having a diameter d comprised between 200 pm and 10 mm, preferably comprised between 250 pm and 8.00 mm, more preferably comprised between 300 pm and 5.50 mm, such as for example comprised between 200 pm and 4.00 mm, or comprised between 250 pm and 3.00 mm, or even comprised between 300 pm and 2.50 mm.

[0076] Last but not least, as mentioned above, by appropriately varying the rotational speed of the collector 50, it is possible to obtain a nanofibre sleeve with a predominantly random or predominantly circumferentially aligned distribution and, consequently, downstream of the heattreatment (step 140), implantable vascular grafts 10 with irregular pores or cavities with dimensions distributed between 2 pm and 100 pm, preferably between 2 pm and 90 pm, more preferably between 2 pm and 80 pm.

[0077] In this context of this description and in the appended claims, by “dimensions of a cavity or pore” is meant to indicate the diameter of the largest sphere that can be inscribed in the cavity or pore.

[0078] In a preferred variant, the electrospinning step 130 comprises modulating the rotational speed of the collector 50 so as to create layers of nanofibres with different densities, i.e. a plurality of sleeves with different densities concentric to each other and integral with each other.

[0079] In the context of the present invention and in the appended claims, by “concentric sleeves” is meant to indicate a series of coaxial sleeves, having different diameters, contained within each other and integral with each other. In particular, it is advantageous to create an intermediate sleeve with a higher density with respect to an outer sleeve and an inner sleeve both with a lower density.

[0080] SECOND EXAMPLE ACCORDING TO THE INVENTION

[0081] A second exemplary implementation of the process 100 according to the present invention is briefly described below, which allowed to manufacture an implantable vascular graft 10 with different pore densities along the thickness t of its own structure and characterised by a length comprised between 60 mm and 90 mm, an internal lumen having diameter equal to about 0.8 mm and a structure thickness t of less than 100 pm.

[0082] The second implementation made use of the same instrumentation as the first implementation example and used the same process parameters, except for the rotational speed of the collector, which was varied. Specifically, the running time of electrospinning step 130 was subdivided into three time intervals (e.g. three intervals of equal duration) and a different rotational speed was used for each time interval as reported in the following table

[0083] The structure thus obtained, once heat-treated, presents, in the innermost and outermost layers, a plurality of irregular cavities with dimensions distributed between 2 pm and 100 pm, which proves ideal for cell nesting and growth, making the resulting structure biomimetic. In the intermediate layer, on the other hand, there is a plurality of irregular cavities with dimensions smaller than 50 pm, e.g. with dimensions distributed between 2 pm and 50 pm, which give the intermediate layer excellent elasticity properties, facilitating a re-closure of the tubular structure of the graft 10 in the event of a syringe needle puncture or laceration and making it particularly suitable for suturing. At the same time, the dimensions of the intermediate layer does not prevent the passage of small-sized particles such as nutrients, metabolites, carbon dioxide and oxygen from the inside to the outside and vice versa.

[0084] In a further preferred variant, the electrospinning step 130 may comprise varying the material of the accelerated nanofibres in the direction of the collector 50, thus making a structure of concentric sleeves that differ in the material they are made up of, as well as possibly also in the density of the material. By way of example, the intermediate layer can be made of a material different from medical grade thermoplastic polyurethane (PU), such as of polytetrafluoroethylene (PTFE), thereby obtaining an intermediate layer capable of giving greater rigidity to the entire structure. In particular, considering that PTFE has a higher melting temperature, during heat-treatment step 140 the outermost and innermost PU layers tend to incorporate the PTFE fibres of the intermediate layer, thus obtaining an overall stronger structure that is particularly suitable in the case of grafting particularly tortuous vessels, i.e. vessels that follow a path with small bending radii, such as for example bending radii of less than 5 times the diameter of the vascular graft. According to further preferred variants, it is also possible to provide structures with a higher number of concentric sleeves that differ in material density and / or in the material they are made up of. By way of example, additional sleeves can be manufactured, e.g. by electrospinning nanofibres made of biodegradable material.

[0085] These additional sleeves, downstream of the heating step 140, can constitute the outermost layer of the vascular graft 10 and this layer can be impregnated with active substances in order to locally release drugs, such as anti-inflammatory drugs and / or cell growth-accelerating drugs, once grafted into the patient.

[0086] The innermost layer, or in general terms the inner surface of the vascular graft 10 according to the present invention, may preferably be impregnated with an anticoagulant active substance to prevent thrombus formation within the vascular graft 10, such as for example heparin.

Claims

CLAIMS1. Implantable vascular graft (10) comprising a hollow tubular structure having a shape with a predominantly elongated development along a longitudinal development axis (B) and at least one tubular structure thickness (t), wherein the hollow tubular structure is made of at least polyurethane (PU) and incorporates within its own structure thickness (t) a plurality of irregular cavities with dimensions to prevent the crossing by particles with dimensions substantially larger than 800 nm, preferably substantially larger than 400 nm, more preferably substantially larger than 100 nm, and to allow the passage by particles with dimensions substantially smaller than 800 nm preferably, substantially smaller than 400 nm, more preferably substantially smaller than 100 nm.

2. Implantable vascular graft (10) comprising a hollow tubular structure having a shape with predominantly elongated development along a longitudinal development axis (B) and at least one tubular structure thickness (t), wherein the hollow tubular structure is made of at least polyurethane (PU) and incorporates within its own structure thickness (t) a plurality of irregular cavities with dimensions varying between 2 pm and 100 pm, preferably between 2 pm and 90 pm, more preferably between 2 pm and 80 pm, wherein the irregular cavities are distributed throughout the at least one structure thickness (t).

3. Implantable vascular graft (10) according to claim 1 or 2, wherein the plurality of irregular cavities has dimensions varying along the at least one structure thickness (t), wherein preferably an inner wall and / or an outer wall of the hollow tubular structure have a plurality of irregular cavities with dimensions distributed between 2 pm and 100 pm, preferably between 2 pm and 90 pm, more preferably between 2 pm and 80 pm, and an intermediate layer of the hollow tubular structure has a plurality of irregular cavities with dimensions distributed between 2 pm and 50 pm.

4. Implantable vascular graft (10) according to claim 3, wherein the intermediate layer is made of a material different from polyurethane (PU), preferably made of polytetrafluoroethylene (PTFE).

5. Implantable vascular graft (10) according to any one of the preceding claims, wherein the hollow tubular structure has an internal lumen with a diameter (d) comprised between 200 pm and 10 mm, preferably comprised between 250 pm and 8.00 mm, more preferably comprised between 300 pm and 5.50 mm; and / or wherein the hollow tubular structure has an internal lumen with a substantially cylindrical shape with a diameter (d) substantially constant along the development axis (B).

6. Implantable vascular graft (10) according to any one of the preceding claims, wherein the at least one structure thickness (t) is comprised between 20 pm and 500 pm,preferably between 20 pm and 300 pm, more preferably between 20 pm and 80 pm; and / or and / or wherein at least one structure thickness (t) is substantially constant along the development axis (B).

7. Implantable vascular graft (10) according to any one of the preceding claims, wherein an inner wall of the hollow tubular structure is impregnated with an active anticoagulant substance.

8. Implantable vascular graft (10) according to any one of the preceding claims, wherein an outer wall of the hollow tubular structure is impregnated with active substances for their localised release.

9. Implantable vascular graft (10) according to any one of the preceding claims, wherein the polyurethane (PU) is of the biocompatible type and / or is medical grade thermoplastic polyurethane.

10. Process (100) for manufacturing an implantable vascular graft (10) with a hollow tubular structure having an internal lumen shape, the process comprising the steps consisting of:- providing (110) a collector (50) with a predominantly elongated development along a collector axis, made of at least partially conductive material, having an external shape substantially corresponding to the internal lumen shape;- placing (120) the collector (50) in rotation around a rotation axis (A) coincident with the collector axis;- dispensing and accelerating by electrospinning (130) at least a plurality of nanofibres, at least part of which is made of medical grade thermoplastic polyurethane, in the direction of the collector (50) placed in rotation, to form at least a sleeve of nanofibres around the collector (50);- heat-treating (140) the at least one nanofibre sleeve for an interval of time sufficient to bring it to a temperature close to or substantially equal to a glass transition temperature of the thermoplastic polyurethane in which the at least part of the plurality of nanofibres is made, thereby resulting in an at least partially crystallized nanofibre structure that make up the implantable vascular graft (10); and- separating (150) the implantable vascular graft (10) thus obtained from the collector (50).

11. Process (100) according to claim 10, wherein the collector (50) is cylindrical and has a collector diameter (de) comprised between 200 pm and 10 mm, preferably comprised between 250 pm and 8.00 mm, more preferably comprised between 300 pm and 5.50 mm.

12. Process (100) according to claim 10 or 11, wherein the rotational step (120) of the collector (50) comprises placing the collector (50) in rotation at a rotational speed that varies during the electrospinning step (130), and wherein, preferably, the rotational speed is initially kept below 200 rpm, preferably below100 rpm, more preferably equal to around 50 rpm; and / or wherein, preferably, the rotational speed is initially kept below 200 rpm for a time interval of at least 100 s, preferably at least 200 s, more preferably equal to around 300 s; and / or wherein, preferably, after a first step at a lower speed, the rotational speed is increased to at least 1,000 rpm, preferably to at least 2,000 rpm, even more preferably to a value equal to around 10,000 rpm.

13. Process (100) according to any one of claims 10 to 12, wherein the heat-treatment step (step 140) comprises placing the nanofibre sleeve in an oven preheated to at least 180 °C for a time comprised between 2 s and 5 min.

14. Process (100) according to any one of claims 10 to 13, wherein the step of dispensing and accelerating by electrospinning (130) takes place:- applying a voltage comprised between 5 kV and 40 kV to a plurality of emitting needles; and / or- dispensing at least one precursor solution of the at least one plurality of nanofibres with a flow rate comprised between 0.1 ml / h and 50 ml / h per needle.

15. Process (100) according to any one of claims 10 to 14, wherein the rotational step (120) of the collector (50) comprises placing the collector (50) in rotation at a rotational speed that varies during the electrospinning step (130) so as to deposit on the collector (50) at least two substantially concentric layers of nanofibres with different densities or to form at least two sleeves of nanofibres with different densities concentric to each other and integral with each other.

16. Process (100) according to any one of claims 10 to 15, wherein the step of electrospinning (130) additionally comprises dispensing and accelerating in the direction of the collector (50) by electrospinning (130) a plurality of nanofibres in at least one second material different from medical grade thermoplastic polyurethane, so as to form at least one sleeve of nanofibres of the second material concentric and integral to the sleeve of thermoplastic polyurethane nanofibres.

17. Vascular graft (10) obtained through the process (100) according to any one of claims 10 to 16, comprising a hollow tubular structure having a shape with a predominantly elongated development along a longitudinal development axis (B) and at least one tubular structure thickness (t), wherein the hollow tubular structure is made of at least polyurethane (PU) and incorporates within its own structure thickness (t) a plurality of irregular cavities with dimensions varying between 2 pm and 100 pm distributed throughout the at least one structure thickness (t).

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