CA2541520A1 - Method and apparatus for coating medical implants - Google Patents

Abstract

A method of coating a non-rotary object with an electrospun coat, the method comprising, dispensing a charged liquefied polymer through at least one dispensing element within an electric field to thereby form a jet of polymer fibers, and moving the dispensing element relative to the object so as to coat the object with the electrospun coat.

Description

METHOD AND APPARATUS FOR COATING MEDICAL IMPLANTS
FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to a method and apparatus for coating an object and, more particularly, to a method and apparatus for coating an object using electrospinning. The present invention is particularly useful for coating medical implants.
Production of fibrous products is described in the literature inter alia using the technique of electrospinning of liquefied polymer, so that products comprising l0 polymer fibers are obtained. Electrospinning is a method for the manufacture of ultra thin synthetic fibers, which reduces the number of technological operations and increases the stability of properties of the product being manufactured.
The process of electrospinning creates a fine stream or jet of liquid that upon proper evaporation of a solvent to solid transition state yields a nonwoven structure.
The fine stream of liquid is produced by pulling a small amount of polymer solution through space by using electrical forces. More particularly, the electrospinning process involves the subjection of a liquefied substance, such as polymer, into an electric field, whereby the liquid is caused to produce fibers that are drawn by electric forces to an electrode, and are, in addition, subjected to a hardening procedure. In the case of liquid which is normally solid at room temperature, the hardening procedure may be mere cooling; other procedures such as chemical hardening (polymerization) or evaporation of solvent may also be employed. The produced fibers are collected on a suitably located precipitation device and subsequently stripped from it. The sedimentation device is typically shaped in accordance with the desired geometry of the final product, which may be for example tubular, flat or even an arbitrarily shaped product.
Examples of tubular fibrous product which can be manufactured via electrospinning are vascular prosthesis, particularly a synthetic blood vessel, and tubes through which a wire or other device or structure may pass or lie. Tubular fibrous products may also be used as various kinds of artificial ducts, such as, for example, urinary, air or bile duct.
Electrospinning can also be used for coating various objects, such as stems and other medical implants. Stems are widely used to provide coronaries with radial support so as to prevent constriction thereof. Nevertheless, clinical data indicates that stems are usually unable to prevent late restenosis beginning at about three months following an angioplasty procedure. Known in the art are stems having a mechanical barrier thereacross, designed to prevent biological material from the lesion to move through the stent and into the lumen during placement of the stmt.
The use of electrospinning for stent coating permits to obtain durable coating with wide range of fiber thickness (from tens of nanometers to tens of micrometers), achieves exceptional homogeneity, smoothness and desired porosity distribution along the coating thickness. Stents themselves do not encourage normal cellular invasion 1o and therefore caxi lead to an undisciplined development of cells in the metal mesh of the stmt, giving rise to cellular hyperplasia. When a stmt is coated by a graft of a porous structure, the pores of the graft component are invaded by cellular tissues from the region of the artery surrounding the stmt graft. Moreover, diversified polymers with various biochemical and physico-mechanical properties can be used in coating.
is With respect to mechanical barriers, coated stems having a mechanical barner can prevent excessive tissue growth from occluding the vessel. U.S. Pat. No.
5,916,264, the contents of which are hereby incorporated by reference, disclose a stmt graft including a sheet of PTFE sandwiched between two metal stents. Although this device has been successful at sealing aneurysms and perforations, it is a bulky device 2o with a significantly larger crossing profile and reduced flexibility compared to a state-of the-art stmt.
Examples of electrospinning methods in stmt graft manufacturing are found in U.S. Patent Nos. 5,639,278, 5,723,004, 5,948,018, 5,632,772, 5,855,598, International Patent Application No. W0249535 and Australian Patent No. AU2249402.
25 It is known that the electrospinning technique is rather sensitive to the changes in the electrophysical and rheological parameters of the solution being used in the coating process. In addition, incorporation of drugs into the polymer in a sufficient concentration so as to achieve a therapeutic effect typically reduces the efficiency of the electrospinning process and causes different defects of the coating. Still in 3o addition, drug introduction into a polymer reduces the mechanical properties of the resulting coating. Although this drawback is somewhat negligible in relatively thick films, for submicron fibers this effect may be adverse.

It is desired that a stmt coat will have good adhesion to the stent metal basis in body liquids, so as not too detached after or during implantation. Further, the elasticity and strength of the stmt coat should be compatible with the enormous inflation of the stmt metal upon opening (about 300-500 %). Additionally, it is desired that the stmt coat will promote better grafting, reduce restenosis risk and optimize medication discharge into implantation-adjacent tissues.
With respect to the above requirements, the properties of prior art stent coats are far less than satisfactory. For example, in electrospinning systems having elongated electrode system, the electric field becomes critically asymmetrical, and the l0 fibers obtain preferential longitudinal orientation. Such coat structure is known to have high anisotropy of mechanical properties in which axial strength (along fiber orientation) is favored over radial strength. It is recognized that radial strength is a crucial parameter, in particular in stmt coat which, as stated, has to comply with significant inflation of the stmt metal. In addition, in prior art electrospinning systems electrostatic repulsion between fibers results in increased opening angle of the jet, an expanded sedimentation area and low rupture strength.
In percutaneous coronary intervention (PCI), including balloon angioplasty and stmt deployment, there is a risk of vessel damage during stmt implantation.
When the stmt is expanded radially in the defective site, the plaques on the wall of the artery 2o cracks and sharp edges thereof cut the surrounding tissue. This causes internal bleeding and a possible local infection, which, if not adequately treated, may spread and adversely affect other parts of the body.
Local infections in the region of the defective site in an artery do not lend themselves to treatment by injecting an antibiotic into the blood stream of the patient, for such treatment is not usually effective against localized infections. A
more common approach to this problem is to coat the wire mesh of the stmt with a therapeutic agent which makes contact with the infected region. However, such one shot treatment is not sufficient to diminish infections, and it is often necessary to administer antibiotic andlor other therapeutic agents for several hours or days, or even months.
The risk of vessel damage during stent implantation may be lowered through the use of a soft stmt serving to improve the biological interface between the stent and the artery and thereby reduce the risk that the stmt will inflict damage during implantation. Examples of polymeric stems or stmt coatings with biocompatible fibers are found in, for example, U.S. Patent Nos. 6,001,125, 5,376,117 and 5,628,788, all of which are hereby incorporated by reference.
U.S. Patent No. 5,948,018 discloses a graft composed of an expensible stmt component covered by an elastomeric polymeric graft component which, because of its stretchability, does not inhibit expansion of the stmt. The graft component is fabricated by electrospinning to achieve porosity hence to facilitate normal cellular growth. However, U.S. Patent No. 5,948,018 fails to address injuries inflicted by the stent in the course of its implantation on the delicate tissues of the artery.
These 1o injuries may result in a local infection at the site of the implantation, or lead to other disorders which, unless treated effectively, can cancel out the benefits of the implant.
Additional prior art of interest include: Murphy et al. "Percutaneous Polymeric Stents in Porcine Coronary Arteries", Circulation 86: 1596-1604, 1992; Jeong et al.
"Does Heparin Release Coating of the Wallstent limit Thrombosis and Platelet is Deposition?", Circulation 92: 173A, 1995; and Wiedermann S.C.
"Intercoronary Irradiation Markedly Reduces Necintimal Proliferation after Balloon Angioplasty in Swine" Amer. Col. Cardiol. 25: 1451-1456, 1995.
Prior art technologies, however, suffer from poor radial strength or having unsuitable porosity for being implanted in the body. Additionally, prior art 2o technologies fail to provide a method of coating a medical implant while being mounted on a delivery system, such as a catheter balloon.
There is thus a widely recognized need for, and it would be highly advantageous to have a method and apparatus for coating medical implants, devoid of the above limitations.
SUMMARY OF THE INVENTION
According to one aspect of the present invention there is provided a method of coating a non-rotary object with an electrospun coat, the method comprising, dispensing a charged liquefied polymer through at least one dispensing element within 3o an electric field to thereby form a jet of polymer fibers, and moving the dispensing element relative to the object so as to coat the object with the electrospun coat.
According to fiuther features in preferred embodiments of the invention described below, the method further comprises translationally moving the object relative to the jet of the polymer fibers so as to uniformly distribute the polymer fibers onto the object.
According to still further features in the described preferred embodiments the translational motion is a harmonic motion.
5 According to still further features in the described preferred embodiments the translational motion is a reciprocation motion.
According to still further features in the described preferred embodiments the object is an expandable tubular supporting element.
According to still further features in the described preferred embodiments the to expandable tubular supporting element comprises a deformable mesh of metal wires.
According to still further features in the described preferred embodiments the expandable tubular supporting element comprises a deformable mesh of stainless steel wires.
According to still further features in the described preferred embodiments the object is a stmt.
According to still further features in the described preferred embodiments the object is a stmt assembly having at least one coat.
According to still further features in the described preferred embodiments the object is a stmt mounted on a stmt delivery system.
2o According to still further features in the described preferred embodiments the object is an implantable medical device.
According to still fiu-ther features in the described preferred embodiments the object is an implantable medical device mounted on a stent delivery system.
According to still further features in the described preferred embodiments the method further comprises mounting the expandable tubular supporting element onto a mandrel, prior to the dispensation of the charged liquefied polymer.
According to still further features in the described preferred embodiments the method further comprises dispensing the charged liquefied polymer through the at least one dispensing element within the electric field, and moving the dispensing 3o element relative to the mandrel so as to coat the mandrel, hence providing an inner coat to the expandable tubular supporting element.

According to still further features in the described preferred embodiments the method further comprises providing at least one adhesion layer onto the expandable tubular supporting element.
According to still further features in the described preferred embodiments the at least one adhesion layer is an impervious adhesion layer.
According to another aspect of the present invention there is provided an apparatus for coating a non-rotary object with an electrospun coat, the apparatus comprising at least one dispensing element being at a potential difference relative to the object, the at least one dispensing element being capable of moving relative to the object while dispensing a charged liquefied polymer within an electric field defined by the potential difference, to thereby form a jet of polymer fibers coating the object.
According to further features in preferred embodiments of the invention described below, the at least one dispensing element is capable of moving along a circular path.
According to still further features in the described preferred embodiments the at least one dispensing element is capable of moving along a helix path.
According to still further features in the described preferred embodiments the at least one dispensing element is capable of moving along a zigzag path.
According to still further features in the described preferred embodiments the 2o at least one dispensing element is designed and constructed such that the electric field moves synchronically with the motion of the at least one dispensing element.
According to still further features in the described preferred embodiments the motion of the at least one dispensing element is selected so as to establish a spiral motion of the jet of the polymer fibers about the object, the spiral motion being characterized by a gradually deceasing radius.
According to still further features in the described preferred embodiments the at least one dispensing element comprises an arrangement of electrodes.
According to still further features in the described preferred embodiments the at least one dispensing element comprises a rotatable ring having at least one capillary.
3o According to still further features in the described preferred embodiments the rotatable ring is made of a dielectric material.
According to still further features in the described preferred embodiments the rotatable ring is made of a conductive material.

According to still further features in the described preferred embodiments the apparatus further comprises a bath for holding a liquefied polymer, the bath being in fluid communication with the at least one dispensing element.
According to still further features in the described preferred embodiments the apparatus further comprises a pump for transferring the liquefied polymer from the bath to the at least one dispensing element.
According to still further features in the described preferred embodiments the apparatus further comprises a mechanism for translationally moving the object relative to the jet of the polymer fibers so as to uniformly distribute the polymer fibers onto the to object.
According to still further features in the described preferred embodiments the apparatus further comprises the charged liquefied polymer and further wherein a medicament is mixed with the charged liquefied polymer and is co-dispensed therewith through the at least one dispensing element, so as to coat the object with an electrospun medicated coat.
According to still further features in the described preferred embodiments the apparatus further comprises a sprayer for distributing compact objects constituting a mendicant therein between the polymer fibers.
According to yet another aspect of the present invention there is provided a 2o method of treating a constricted blood vessel, the method comprising: (a) providing a stmt assembly; (b) dispensing a charged liquefied polymer through at least one dispensing element within an electric field to thereby form a jet of polymer fibers, and moving the dispensing element relative to the stmt assembly so as to coat the stmt assembly with an electrospun coat; and (c) placing the stmt assembly in the constricted blood vessel.
According to further features in preferred embodiments of the invention described below, the method further comprises expanding the stent assembly so as to dilate tissues surrounding the stent assembly in a manner such that flow constriction is substantially eradicated.
3o According to still further features in the described preferred embodiments the motion of the at least one dispensing element is selected so as to establish a spiral motion of the jet of the polymer fibers about the stmt assembly, the spiral motion being characterized by a gradually deceasing radius.

According to still further features in the described preferred embodiments the method further comprises translationally moving the stmt assembly relative to the jet of the polymer fibers so as to uniformly distribute the polymer fibers onto the stent assembly.
According to still further features in the described preferred embodiments a medicament is mixed with the charged liquefied polymer and is co-dispensed therewith through the at least one dispensing element, so as to coat the object with an electrospun medicated coat.
According to still further features in the described preferred embodiments the to medicament is dissolved in the charged liquefied polymer.
According to still further features in the described preferred embodiments the medicament is suspended in the charged liquefied polymer.
According to still further features in the described preferred embodiments the medicament is constituted by particles embedded in the polymer fibers.
is According to still further features in the described preferred embodiments the method further comprises constituting a mendicant into compact objects and distributing the compact objects between the polymer fibers.
According to still further features in the described preferred embodiments the medicament is heparin.
2o According to still further features in the described preferred embodiments the medicament is a radioactive compound.
According to still further features in the described preferred embodiments the medicament is silver sulfadiazine.
According to still further features in the described preferred embodiments the 25 compact objects are capsules.
According to still further features in the described preferred embodiments the compact objects are in a powder form.
According to still further features in the described preferred embodiments the distributing of the compact objects is by spraying.
3o According to still further features in the described preferred embodiments the method further comprises providing at least one additional coat on the electrospun coat.

The present invention successfully addresses the shortcomings of the presently known configurations by providing a method and apparatus for coating a non-rotary object with an electrospun coat Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, to and examples are illustrative only and not intended to be limiting.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention 2o in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.
In the drawings:
FIG. 1 is a schematic illustration of a prior art electrospinning apparatus;
FIG. 2a is a flowchart diagram of a method of coating a non-rotary object with an electrospun coat, according to a preferred embodiment of the present invention;
FIGs. 2b-a are schematic illustrations of paths along which a dispensing element can move, according to a preferred embodiment of the present invention;
FIG. 2f is a schematic illustration of a spiral trajectory of a polymer fiber, 3o according to a preferred embodiment of the present invention;
FIG. 3 is a cross-sectional view of a stmt assembly according to a preferred embodiment of the present invention;

FIG. 4a is an end view the stent assembly, according to a preferred embodiment of the present invention;
FIG. 4b is an end view of a stent assembly which further comprises at least one adhesion layer, according to a preferred embodiment of the present invention;
5 FIG. 5 is a tubular supporting element which is designed and constructed for dilating a constricted blood vessel in a body vasculature, according to a preferred embodiment of the present invention;
FIG. 6 is a portion of the tubular supporting element of Figure 5 comprising a deformable mesh of metal wires, according to a preferred embodiment of the present 10 invention;
FIG. 7 is a stmt assembly, manufactured according to the teachings of the present invention, occupying a defective site in an artery;
FIG. 8 is a portion of a non-woven web of polymer fibers produced according to a preferred embodiment of the present invention;
FIG. 9 is a portion of a non-woven web of polymer fibers which comprises a pharmaceutical agent constituted by compact objects and distributed between the electrospun polymer fibers;
FIG. 10 is a schematic illustration of an apparatus for coating a non-rotary object with an electrospun coat, according to a preferred embodiment of the present 2o invention; and FIG. 11 is a flowchart diagram of a method of treating a constricted blood vessel, according to a preferred embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is of a method and apparatus for coating an object which can be implantable medical device. Specifically, the present invention can be used to provide an electrospun coat to non-rotary objects, such as, but not limited to, stems or other implantable medical devices while being mounted on a delivery system (e.g., a stmt delivery system) or a portion thereof. The present invention is further of a 3o method of treating a constricted blood vessel.
For purposes of better understanding the present invention, as illustrated in Figures 2-11 of the drawings, reference is first made to the construction and operation of a conventional (i.e., prior art) electrospinning apparatus as illustrated in Figure 1.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description arid should not be regarded as limiting.
Referring now to the drawings, Figure 1 illustrates a conventional electrospinning apparatus for manufacturing a nonwoven material, generally referred to to herein as apparatus 1.
Apparatus 1 includes a dispenser 2 which can be, for example, a bath provided with one or more capillary apertures 4. Dispenser 2 serves for storing the polymer to be spun in a liquid form (dissolved or melted). Dispenser 2 is positioned at a predetermined distance from a precipitation electrode 6, defining a first axis therebetween. Precipitation electrode 6 serves for forming a structure thereupon.
Precipitation electrode 6 is typically manufactured in accordance with the geometrical properties of the final product which is to be fabricated. For example, precipitation electrode 6 can be a mandrel having a longitudinal axis 3 which can be used for manufacturing tubular structures.
2o Dispenser 2 is typically grounded, while precipitation electrode 6 is connected to a source of high voltage (not shown in Figure 1), preferably of negative polarity, thus forming an electric field between dispenser Z and precipitation electrode 6.
Alternatively, precipitation electrode 6 can be grounded while dispenser 2 is connected to a source of high voltage with positive polarity.
To generate a nonwoven material, the liquefied polymer is extruded, for example under the action of hydrostatic pressure, or using a pump (not shown in Figure 1), through capillary apertures 4 of dispenser 2. As soon as meniscus of the extruded liquefied polymer forms, a process of solvent evaporation or cooling starts, which is accompanied by the creation of capsules with a semi-rigid envelope or crust.
3o An electric field, occasionally accompanied by a unipolar corona discharge in the area of dispenser 2, is generated by the potential difference between dispenser 2 and precipitation electrode 6. Because the liquefied polymer possesses a certain degree of electrical conductivity, the above-described capsules become charged. Electric forces of repulsion within the capsules lead to a drastic increase in hydrostatic pressure. The semi-rigid envelopes are stretched, and a number of point micro-ruptures are formed on the surface of each envelope leading to spraying of ultra-thin jets of liquefied polymer from dispenser 2.
s Under the effect of a Coulomb force, the jets depart from dispenser 2 and travel towards the opposite polarity electrode, i.e., precipitation electrode 6.
Moving with high velocity in the inter-electrode space, the jet cools or solvent therein evaporates, thus forming a jet of polymer fibers, collected on the surface of precipitation electrode 6, thus forming a non-woven structure thereupon. Tubular non-woven structures are to conventionally produced by rotating precipitation electrode 6 about longitudinal axis 3 during the electrospinning process, so as to circularly coat precipitation electrode 6.
Typical electrospinning processes (e.g., as employed by apparatus 1) suffer from several limitations.
First, as will be appreciated by a skilled artisan, when precipitation electrode 6 15 has a small radius of curvature, the polymer fibers tend to align axially along longitudinal axis 3. In such cases the resulting structure has an axial strength which is favored over the radial strength. Thus, small diameter products, have limited radial strength when manufactured via conventional electrospinning processes.
Second, conventional electrospinning processes for non-woven tubular 2o structures are limited to the manufacturing of hollow tubes. This is done either by coating precipitation electrode 6 by the electrospun coat or by mounting a tubular member on precipitation electrode 6 prior to the initiation of the electrospinning process. In any event, the final product, once removed from precipitation electrode 6, is hollow. However, it is often desired to produce structures having additional 25 members designed to engage the internal volume of the structure, it is recognized that with prior art electrospinning techniques, such additional internal members can only be inserted into the non-woven structure after the structure is removed from precipitation electrode 6. For example, with conventional electrospinning processes, it is not possible to coat a stmt if it is already mounted on a stmt delivery system.
3o Third, in a typical electrospinning process the electric field, generated between dispenser 2 and precipitation electrode 6, is static and the charged polymer fibers, which tend to align with the field lines, move along static trajectories. This limits the capability to control fiber orientation hence the strength of the final product.

While conceiving the present invention it has been hypothesized, and while reducing the present invention to practice it has been realized, that objects can be coated by allowing the dispensing element of the electrospinning apparatus to move along a predetermined path while keeping the objects in a non-rotary or static state.
The advantage of the present embodiment in which the objects are non-rotary is that there is no need to mount the objects on a rotating electrode prior to the electrospinning process, thus allowing the coating of non-hollow as well as hollow objects. For example, the present embodiment can be used for providing an electrospun coat on stents or other medical implantable devices, either alone or while 1o being mounted on a suitable delivery system, e.g., a stmt delivery system, such as, but not limited to, a catheter balloon. This embodiment is useful when it is desired to improve strength, form a mechanical barrier and/or incorporate medicaments into commercially available medical implantable devices which are typically supplied by the vendor as "one unit products" in which the medical implantable devices are mounted on or integrated with additional members or devices.
Reference is now made to Figure 2a, which is a flowchart diagram of a method of coating a non-rotary object, according to a preferred embodiment of the present invention. In a first step on the method, designated in Figure 2 by Block 7, a charged liquefied polymer is dispensed through at least one dispensing element within an 2o electric field, to thereby form a jet of polymer fibers. In a second step of the method, designated by Block 8, the dispensing element is moved relative to the object so as to coat the object with the electrospun coat. While moving along the predetermined path, the dispensing elements) can change the direction and/or magnitude of the electric field. These changes can be tailored in accordance with the desired orientation of the polymer fibers on the object. As further detailed hereinabove.
As stated, the dispensing element can be moved along a predetermined path.
The path is preferably selected so as to coat the entire object or selected portions thereof, as desired. For example, referring, to Figures 2b-d, when the object has a tubular shape (e.g., a cylinder) the dispenser can be moved along a helix path (Figure 2b), a circular path (Figure 2c), a zigzag path (Figure 2d-e) and the like.
The path and the parameters characterizing the path are preferably selected according to the desired orientation of fibers on the object. Several sweeps of the dispensing element along the objects can be employed so as to improve the homogeneity of the electrospun coat.

The number of seeps is preferably selected according to the desired porosity of the coat, where larger number of sweeps corresponds to lower average pore size.
Additionally, the density of the fibers and/or the type of liquefied polymer can be changes from one sweep to the other thereby to provide a multilayer coat, as further detailed hereinunder.
The motion of the dispensing element can be supplemented by a translational motion (e.g., reciprocation motion, harmonic motion, etc.) of the object relative to the jet of polymer fibers. This embodiment is particularly useful when the motion path of the dispensing element is planar (e.g., a circular path), such that upon reciprocal travel to of the object relative to the motion plane of the dispensing element the fibers are re-distributed along the object and the homogeneity of the coat is improved.
According to the electrospinning principles, the electrical field is generated by a potential difference between the dispensing element and the object. Typical potential difference is from about 20 kV to about 50 kV. Such potential difference can be established, e.g., by grounding the dispensing element and placing the object in a negative potential or in any other electrostatic configuration which ensures the motion of the charged liquefied polymer from the dispensing element to the object.
When the object comprises conductive parts (e.g., a metal mesh of a stmt) the conductive parts can be connected to a voltage source, preferably of negative polarity. When the object 2o is non conductive, or if desired, the object can be mounted on a precipitation electrode (e.g., a mandrel), connected to a voltage source.
When the fibers moves in space they are subjected to friction forces which result from collisions between molecules of the medium surrounding the object (typically air) and molecules of the fibers. The higher the density of the surrounding medium the larger are the friction forces. According to a preferred embodiment of the present invention the velocity of the dispensing element is selected such that the the polymer fibers acquire a sufficient transverse velocity relative to the axis defined by the dispensing element and the object (see, e.g., axis S in Figure 1). A
typical linear velocity of the dispensing element is from about 100 cm/sec to about 3000 cmlsec.
3o For a rotary motion of the dispensing element (e.g., helical, circular), a typical rotation frequency is from about 100 rpm to about 1200 rpm.
As used herein the term "about" refers to ~ 10 %.

The trajectory of the polymer fibers in the medium surrounding the objects thus depends on (i) the electrical force applied by the electric field; (ii) the friction force applied by molecules of the surrounding medium; and (iii) the transverse velocity of the fibers. As will be appreciated by one of ordinary skill in the art, when 5 the electrospinning process is performed in a vacuum, there is no friction force and the trajectory of the polymer fibers depends only on the electric force and the transverse velocity. Thus, when the electrospinning process is performed in gaseous medium the trajectory of the polymer fiber is curvilinear, while for a process performed in a vacuum, due to the lack of friction, the trajectory is substantially rectilinear.
to Beside the transverse velocity of the fibers, they also accelerate under the influence of the electric field in the direction of the electric field lines.
Thus, the direction of motion of the fibers at a given instant is the (vector) sum of the transverse velocity and the velocity acquired in the direction of the electric field. For example, when the dispensing element moves along a circular path, the jet of fibers moves along 15 a spiral motion, characterized by a gradually deceasing radius. A
representative example of a spiral trajectory is shown in Figure 2f.
It was found by the present inventors that although the polymer fibers have relatively low mass per unit length, the momentum acquired by the fibers due to tangent movement becomes sufficient to oppose the electrical field perturbing forces and to stabilize the movement of the fibers in space. For a tubular object and a circular motion of the dispensing element, it was found that at the aforementioned circular frequencies, the acquired momentum of the fibers is sufficient to provide a coat in which the fibers have a predominant azimuthal spatial orientation. In this respect, higher frequencies result in higher is azimuthal orientation extent.
According to a preferred embodiment of the present invention the motion characteristics (e.g., path, linear velocity, frequency) of the dispensing element are selected such that at least 60 % of the polymer fibers, more preferably at least 80 %, most preferably at least 90 % has an azimuthal orientation with respected to the longitudinal axis of the object. Additionally or alternatively, the motion characteristics (e.g., path, linear 3o velocity, frequency) of the dispensing element are selected such that the electrospun coat is capable of bearing a radial expansion of at least 300 %, more preferably at least 400 %, most preferably at least 500 % without being ruptured.

It was further found by the present inventors that the motion of the dispensing element substantially narrows the jet spraying angle, thereby producing more concentrated jet resulting in a low average pore size of the final coat. The jet angle can further be narrowed by a judicious selection of the geometrical shape of the s dispensing element thereby the magnitude and direction of the electric field near the object and along the trajectory of the fibers. According to a preferred embodiment of the present invention the motion and/or shape of the dispensing element is selected such that the spraying angle is narrowed by at least 10 %, more preferably at least 30 % and most preferably at least 60 %. Thus, the combination of the electric force, to friction force, transverse velocity and preferably the translational motion of the objects allows controlling the orientation, porosity as well as the density of the final coat.
For example, in applications in which the electrospun coat is applied on a stmt, or other medical tubular implant, it is desired that the properties of the coat are suitable for implantation. Specifically, for high radial strength, a predominant azimuthal 15 orientation of the fibers is preferred, which azimuthal orientation can be obtained, as stated, by selecting a circular motion for the dispensing element.
Additionally, for blood vessel implants, such as stents and vascular prostheses, the porosity is selected so as to accommodate cells migrating from the surrounding tissues and to facilitate the proliferation of these cells while, at the same time, preventing undesired chemical 2o materials and plaque debris from entering the blood vessel lumen during placement of the stent or prosthesis.
Furthermore, the controllable porosity of the present embodiment allows to design local drug delivery elements, whereby the coat may be incorporated with a mendicant or another pharmaceutical agent. In such devices, the porosity of the coat is 25 preferably designed both to bear the independent drug load and to serve as a barrier controlling the drug release rate.
The embodiments of the present invention can be used for coating expandable tubular supporting elements of stems, as well as stmt assemblies which already have a preliminary coat. In any event, the above method can be used for providing single as 3o well as multilayer coats, such as the coats disclosed in International Patent Application No. PCT/IL01/01171, the contents of which are hereby incorporated by reference.
Reference is now to Figure 3 which is a schematic illustration of a cross-sectional view of a scent assembly, coated using selected steps of the method of the present invention. The stmt assembly comprises an expendable tubular supporting element 10 and at least one coat 12, having a predetermined porosity. Coat 12 comprises an inner coat 14, lining an inner surface of element 10 and an outer coat 16, covering an outer surface of element 10. Figure 4a illustrates an end view of the stmt assembly, showing element 10, internally covered by inner coat 14 and externally covered by outer coat 16. With reference to Figure 4b, coat 12 may further comprise at least one adhesion layer 15, for adhering the components of the stmt assembly as further detailed hereinafter.
Each of inner 14 and outer 16 coats can be provided using the above method to by moving the dispensing element relative to expandable supporting element 10.
Preferably, inner 14 and outer 16 coats are made of different liquefied polymers and have predetermined porosities, which may be different or similar as desired.
According to a preferred embodiment of the present invention, the liquefied polymer of inner 14 and/or outer 16 coats can be mixed with a mendicant or a pharmaceutical agent prior to the electrospinning process. The mendicant can be either dissolved or suspended in the liquefied polymer.
There is more than one way to provide outer coat 16. In one embodiment, element 10 is mounted on a precipitation electrode (e.g., a mandrel), prior to the electrospinning process. In this embodiment, the precipitation electrode function both 2o as a carrier for element 10 and as a conductive element to which a high voltage is applied to establish the electric field. As a consequence, the polymer fibers emerging from the dispensing element are projected toward the precipitation electrode and form outer coat 16 on tubular supporting element 10. This coating covers both the metal wires of element 10 and gaps between the wires.
In another embodiment, element 10 serves as a precipitation electrode. In this embodiment, polymer fibers are exclusively attracted to the wires of tubulax supporting element 10 exposing the gaps therebetween. The resultant coated stmt therefore has pores which serve for facilitating pharmaceutical agent delivery from the stmt assembly into body vasculature.
3o According to a preferred embodiment of the present invention inner coat 14 is provided as follows. First, the electrospinning process is employed so as to directly coat the mandrel, so as to form inner coat 14 thereon. Once the mandrel is coated, the electrospinning process is temporarily ceased and element 10 is slipped onto the mandrel and drawn over inner coat 14. Outer coat 16 is then provided by resuming the electrospinning process onto element 10.
Since the operation for providing inner coat 14 demands a process cessation for a certain period, a majority of solvent contained in inner coat 14 may be evaporated.
This may lead to a poor adhesion between the components of the stmt assembly, once the process is resumed, and might result in the coating stratification following stmt graft opening.
The present invention successfully addresses the above-indicated limitation by two optimized techniques. According to one technique, the outer sub-layer of inner to coat 14 and the inner sub-layer of outer coat 16 are each made by electrospinning with upgraded capacity. A typical upgrading can may range from about 50 % to about 100 %. This procedure produce a dense adhesion layer made of thicker fibers with markedly increased solvent content. A typical thickness of the adhesion layer ranges between about 20 pm and about 30 ~tm, which is small compared to the overall diameter of the stmt assembly hence does not produce considerable effect on the coats general parameters. According to an alternative technique, the adhesion layer comprises an alternative polymer with lower molecular weight than the major polymer, possessing high elastic properties and reactivity.
Other techniques for improving adhesion between the layers and tubular 2o supporting element 10 may also be employed. For example, implementation of various adhesives, primers, welding, chemical binding in the solvent fumes can be used. Examples for suitable materials are silanes such as aminoethyaminopropyl triacytoxysilane and the like.
The advantage of using the electrospinning method for fabricating inner coat 14 and outer coat 16 the is flexibility of choosing the polymer types and fibers thickness, thereby providing a final product having the required combination of strength, elastic .and other properties as delineated herein. In addition, an alternating sequence of the sub-layers forming at coat 12, each made of differently oriented fibers, determines the porosity distribution nature along the stmt assembly wall thickness.
3o Still in addition, the electrospinning method has the advantage of allowing the incorporation of various chemical components, such as pharmaceutical agents, to be incorporated in the fibers by mixing the pharmaceutical agents in the liquefied polymers prior to electrospinning.

Reference is now made to Figure 5 which is a schematic illustration of tubular supporting element 10 designed and constructed for dilating a constricted blood vessel in the body vasculature. Element 10 expands radially thereby dilates a constricted blood vessel. According to a preferred embodiment of the present invention, the expansibility of the stmt assembly may be optimized by a suitable construction of element 10 and coat 12. The construction of element 10 will be described first, with reference to Figure 6, and the construction of coat 12 will be described thereafter.
Hence, Figure 6 illustrates a portion of element 10 comprising a deformable mesh of metal wires 18, which can be, for example, a deformable mesh of stainless l0 steel wires. When the stmt assembly is placed in the desired location in an artery, element 10 rnay be expanded radially, to substantially dilate the arterial tissues surrounding the stent assembly to eradicate a flow constriction in the artery.
The expansion may be performed by any method known in the art, for example by using a balloon catheter or by forming element 10 from a material exhibiting temperature-activated shape, memory properties, such as Nitinol. According to a presently preferred embodiment of the invention, the polymer fibers forming coat 12 are elastomeric polymer fibers which stretch as element IO is radially expanded.
According to a preferred embodiment of the present invention inner coat 14 and outer coat 16 are coextensive with element 10, i.e., tubular supporting element 10 is 2o substantially coated. Alternatively, inner coat 14 and/or outer coat 16 may be shorter in length than element 10, in which case at least one end of element 10 is exposed.
Reference is now made to Figure 7, which illustrates the stmt assembly occupying a defective site 20 in an artery. The outer diameter of the stmt assembly in its unexpanded state, including outer coat 16, is such that it ensures transporting of the stmt assembly through the artery to defective site 20, for example by a catheter. The expending range of the stmt assembly is such that when in place at defective site 20, the expanded assembly then has a maximum diameter causing the arterial tissues surrounding the stent assembly to be dilated to a degree eradicating the flow constriction at the site.
3o Implantation of the stmt assembly in a blood vessel may result in disorders in the blood vessel, for example an injury inflicted on tissues of the blood vessel upon the implantation, restenosis, in-scent stenosis and hyper cell proliferation. To treat such injury or other disorders, coat 12 may comprise a medicament for delivery of the medicament into a body vasculature. Hence, coat 12 not only serves to graft the assembly to the artery but also functions as a reservoir for storing the medicament to be delivered over a prolonged time period. Within the above diameter limitation, the larger the aggregate volume of coat 12, the larger its capacity to store the medicament.
5 Reference is now made to Figure 8 which illustrates a portion of a non-woven web of polymer fibers produced according to a preferred embodiment of the present invention. Fibers 22, 24 and 26 intersect and are joined together at the intersections, the resultant interstices rendering the web highly porous. Since electrospun fibers are ultra-thin, they have an exceptionally large surface area, which allows a high quantity 10 of pharmaceutical agents and medicaments to be incorporated thereon. The surface area of the electrospun polymer fibers approaches that of activated carbon, thereby making the non-woven web of polymer fibers an efficient local drug delivery system.
The preferred mechanism of medicament release from the coat is by diffusion, regardless of the technique employed to embed the medicament therein. The duration 15 of therapeutic drug release in a predetermined concentration depends on several variants, which may be controlled during the manufacturing process. One variant is the chemical nature of the carrier polymer and the chemical means binding the medicament to it. This variant may be controlled by a suitable choice of the polymers) used in the electrospinning process. Another variant is the area of contact 2o between the body and the medicament, which can be controlled by varying the free surface of the electrospun polymer fibers. Also affecting the duration of medicament release is the method used to incorporate the medicament within at least one coat 12, as is further described herein.
According to a preferred embodiment of the present invention, the coat comprises a number of sub-layers. Depending on their destination, the sub-layers can be differentiated by fiber orientation, polymer type, medicament incorporated therein and desired release rate thereof. Thus, medicament release during the first hours and days following implantation may be achieved by incorporating a solid solution, containing a medicament such as anticoagulants and antithrombogenic agents, in a 3o sub-layer of readily soluble biodegradable polymer fibers. During the first period following implantation the medicament that releases includes anticoagulants and antithrombogenic agents.

Referring now again to Figure 8, the medicament may be constituted by particles 28 embedded in the electrospun polymer fibers forming a sub-layer of at least one coat 12. This method is useful for medicament release during the first post-operative days and weeks. To this end, the medicament can include antimicrobials or antibiotics, thrombolytics, vasodilators, and the like. The duration of the delivery process is effected by the type of polymer used for fabricating the corresponding sub-layer. Specifically, optimal release rate is ensured by using moderately stable biodegradable polymers.
Reference is now made to Figure 9 illustrating an alternative method for to incorporating the medicament in the coat, ensuring medicament release during the first post-operative days and weeks. Thus, according to a preferred embodiment of the present invention, the medicament is constituted by compact objects 30 distributed between the electrospun polymer fibers of the coat. Compact objects 30 may be in any known form, such as, but not limited to, moderately stable biodegradable polymer capsules.
The present invention is also provides a method of releasing medicament, which may last, from several months to several years. According to a preferred embodiment of the present invention the medicament is dissolved or encapsulated in a sub-layer made of biosatable fibers. The rate diffusion from within a biostable sub-layer is substantially slower, thereby ensuring a prolonged effect of medicament release. Medicaments suitable for such prolonged release include, without limitation, antiplatelets, growth-factor antagonists and free radical scavengers.
Thus, the sequence of medicament release and impact longevity of a certain specific medicaments is determined by the type of drug-incorporated polymer, the method in which the medicament is introduced into the electrospun polymer fibers, the sequence of layers forming the coat, the matrix morphological peculiarities of each layer and the concentration of the medicament.
Reference is now made to Figure 10, which is a schematic illustration of an apparatus 50 for coating a non-rotary object 52 with an electrospun coat, according to a preferred embodiment of the present invention. Apparatus 50 comprises at least one dispensing element 37 being at a potential difference relative to object 52, dispensing element 53 is capable of moving relative to object 52 while dispensing the charged liquefied polymer as further detailed hereinabove. Dispensing element 37 may be for example, an arrangement of electrodes or a rotatable ring 45 having at least one capillary 46, preferably radially oriented. Ring 45 can be made of a dielectric or conductive material as desired. Capillaries 46 are made of conductive material and in electrical communication thereamongst. Preferably, the number of capillaries is from 1 capillary to more than 10 capillaries, more preferably 2-4 capillaries, most preferably 3 capillaries. The diameter of ring 45 and the length of capillaries 46 are preferably selected such that the distance between object 52 and tip 51 of capillary 46 is from about 100 mm to about 250 mm, more preferably from about 120 mm to about 180 mm, most preferably about 150 mm.
According to a preferred embodiment of the present invention dispensing element 37 is connected to a shaft 47 having at least one arm 48. Arms 48 and shaft 47 are preferably hollow elements to allow flow of the liquefied polymer therethrough.
Alternatively a system of flexible tubes can be used to establish fluid communication between dispensing element 37 and a bath 41 which holds the liquefied polymer.
Shaft 47 is preferably positioned between one or more bearings 58 and serves for mechanically connecting dispensing element 37 with an electric drive 54.
Apparatus 50 may further comprise a mandrel 42 which may be connected to a power supply 43 in embodiments in which mandrel 42 serves as conductive electrodes. Mandrel 42 or object 52 (in embodiments in which mandrel 42 is not used) 2o is preferably operatively associated with a mechanism 56 for translationally moving object 52 as further detailed hereinabove.
According to a preferred embodiment of the present invention apparatus 50 further comprises a pump 40, connected to bath 41 for drawing the liquid polymer stored in bath 41 into dispensing element 37. Apparatus 50 may further comprise one or more filters 49, through which the liquefied is transferred via shaft 47 and arm 48 into element 37.
Optionally and preferably, apparatus 50 comprises a sprayer 57 for distributing compact objects (e.g., objects 30) constituting a mendicant therein between the polymer fibers, as further detailed hereinabove.
Reference is now made to Figure 1 l, which is a flowchart diagram of a method of treating a constricted blood vessel, according to a preferred embodiment of the present invention. In a first step a first step on the method, designated in Figure 11 by Block 60, a stmt assembly is provided. In a second step, designated by Block 62, a charged liquefied polymer is dispensed through a moving dispensing element as further detailed hereinabove. In a third step of the method, designated by Block 64, the stent assembly is placed in the constricted blood vessel, for example, using a catheter balloon or other stmt delivery system. In a forth step of the method, designated by Block 66, the stmt assembly is preferably expanded so as to dilate the arterial tissues .surrounding the stmt assembly to a degree eradicating the flow constriction of the blood vessel.
It should be understood, that although the invention has been described in conjunction with medical implants, other medical implants, not necessarily of tubular l0 structure, may be coated using the techniques of the present invention. For example, grafts and patches, which may be coated prior to procedure of implantation or application can be drug-loaded and enjoy the advantages as described herein.
The coat may be made from any known biocompatible polymer. In the layers which incorporate medicament, the polymer fibers are preferably a combination of a biodegradable polymer and a biostable polymer.
Representative examples of biostable polymers with a relatively low chronic tissue response include, without limitation, polycarbonate based aliphatic polyurethanes, siloxane based aromatic polyurethanes, polydimethylsiloxane and other silicone rubbers, polyester, polyoleflns, polymethyl- methacrylate, vinyl halide 2o polymer and copolymers, polyvinyl aromatics, polyvinyl esters, polyamides, polyimides, polyethers and many others that can be dissolved in appropriate solvents and electrically spun on the stmt.
Biodegradable fiber-forming polymers that can be used include poly (L-lactic acid), poly (lactide-co-glycolide), polycaprolactone, polyphosphate ester, poly (hydroxy- butyrate), poly (glycolic acid), poly (DL-lactic acid), poly (amino acid), cyanocrylate, some copolymers and biomolecules such as DNA, silk, chitozan and cellulose.
These hydrophilic and hydrophobic polymers which are readily degraded by microorganisms and enzymes are suitable for encapsulating material for drugs.
In 3o particular, Polycaprolacton has a slower degradation rate than most other polymers and is therefore especially suitable for controlled-release of medicament over long periods of time scale ranging from about 2 years to about 3 years.

Suitable pharmaceutical agents that can be incorporated in at least one coat include heparin, tridodecylmethylammonium-heparin, epothilone A, epothilone B, rotomycine, ticlopidine, dexamethasone, caumadin, and other pharmaceuticals falling generally into the categories of antithrombotic drugs, estrogens, corticosteroids, cytostatics, anticoagulant drugs, vasodilators, and antiplatelet drugs, trombolytics, antimicrobials or antibiotics, antimitotics, antiproliferatives, antisecretory agents, non-sterodial antiflammentory drugs, grow factor antagonists, free radical scavengers, antioxidants, radiopaque agents, immunosuppressive agents and radio-labeled agents.
to It is expected that during the life of this patent many relevant implantable medical devices will be developed and the scope of the term implantable medical device is intended to include all such new technologies a priori.
Additional objects, advantages and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting. Additionally, each of the various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below finds experimental support in the following examples.
EXAMPLES
Reference is now made to the following examples, which together with the above descriptions illustrate the invention in a non limiting fashion.
Materials, Devices a~zd Methods A Carbothane PC-3575A was purchased from Thermedics Polymer Products, and was used for coating. This polymer has satisfactory fiber-forming abilities, it is biocompatible and is capable of lipophilic drug incorporation. A mixture of dimethylformamide and toluene of ratio ranging from 1:1 to 1:2 was used as a solvent 3o in all experiments.
A PHD 2000 syringe pump was purchased from Harvard Apparatus and was used for feeding the polymer solutions into the in the electrospinning apparatus. The dispensing element included a hollow ring, 400 mm in diameter, made of stainless tube. Three capillaries, 25 mm in length and 0.5 mm in internal diameter, were symmetrically disposed the internal surface of a ring. The flow-rate at each capillary was between 1 ml/min and 5 ml/min. The dispensing element was connected to the pump with flexible polytetrafluorethylene tubes and was grounded. A rod of polished 5 stainless steel, 1.05 mm in diameter and 60 mm in length, was used as a mandrel and was kept at a potential of 30 kV. The mandrel was positioned in the geometrical center of the ring, about 175 mm from the capillaries ends.
The ring was rotated at a frequency of 60-1000 rpm and the mandrel was actuated to a longitudinal reciprocation motion, 30 - 40 mm in amplitude and to motions/min in frequency.

A stent assembly, 16 mm in length was manufactured using a stainless-steel stmt, 3.4 mm in diameter in its expanded state and 1.1 mm in diameter in its non-is expanded state, as the tubular supporting element. The used stainless-steel stmt is typically intended for catheter and balloon angioplasty. For adhesion upgrading in polymer coating, the stmt was exposed to 160-180 kJ/m2 corona discharge, rinsed by ethyl alcohol and deionized water, and dried in a nitrogen flow. The solution parameters were: concentration of 8 %, viscosity of 560 cP and conductivity of 20 0.8 mS. For the pharmaceutical agent, heparin in tetrahydrofurane solution was used, at a concentration of 250 Ulml. The polymer to heparin-solution ratio was 100:1. The dispensing element rotating frequency was 60 rpm.
A two step coating process was employed. First, the mandrel was coated by electrospinning with polymer fiber layer the thickness of which was about 20 ~,m.
25 Once the first step was accomplished, the tubular supporting element was put over the first coat hence an inner coating for the tubular supporting element was obtained.
Second, an outer coating was applied to the outer surface of the tubular supporting element. The thickness of the outer coat was about 40~,m.
The stent assembly was removed from the mandrel, and was placed for about 30 seconds into the saturated dimethylformamide (DNTF) vapor atmosphere at 45 °C, so as to ensure upgrading the adhesion strength between the inner coat and the outer coat. To remove solvent remnants, the stmt was exposed to partial vacuum processing for about 24 hours. Once the coating process was completed, the coated stent was subjected to elasticity tests by radial inflation.
The fibers of the resultant coat had a random orientation. The coat was capable of bearing a 320 % radial expansion without being ruptured.

A stmt assembly was manufactured as described in Example 1, with an increased rotation frequency of 600 rpm. About 80 % of the fibers of the resultant coat had an azimuthal orientation. The coat was capable of bearing a 410 %
radial expansion without being ruptured.

A stmt assembly was manufactured as described in Example 1, with an increased rotation frequency of 1000 rpm. The resultant coat was more uniform and the fibers were mostly azimuthally oriented: about 95 % of the fibers had an azimuthal orientation, and the coat was capable of bearing a 550 % radial expansion without being ruptured.

2o A stmt assembly was manufactured as described in Example 2, with a heparin solution at a concentration of 380 U/ml mixed with 15 % poly (DL-Lactide-CD-Glycolide) solution in chloroform. The change in the pharmaceutical agent did not affect the quality of the coat.

A stmt assembly was manufactured from the materials described in Example 1, with 60 wm inner coat of biodegradable heparin-loaded polymer, and an outer coat of polyurethane fibers completing an overall coat thickness of 100 ~,m. The rotation frequencies of 60 rpm and 1000 rpm were used for providing the inner and outer coats, 3o respectively. The resulting inner coat had a predominant axial (longitudinal) orientation, whereas the outer coat had a predominant azimuthal orientation, thus verifying that fiber orientation can be controlled by the dispensing element rotation frequency.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be s provided separately or in any suitable subcombination.
Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

Claims (92)

1. A method of coating a non-rotary object with an electrospun coat, the method comprising, dispensing a charged liquefied polymer through at least one dispensing element within art electric field to thereby form a jet of polymer fibers, and moving said dispensing element relative to said object to provide said polymer fibers with a sufficient transverse velocity relative to an axis defined by said dispensing element and the object, so as to coat the object with the electrospun coat.

2. The method of claim 1, wherein said moving said at least one dispensing element is, at least in part, in a helix path.

3. The method of claim 1, wherein said moving said at least one dispensing element is, at least in part, in a circular path.

4. The method of claim 1, wherein said moving said at least one dispensing element is, at least in part, in a zigzag path.

5. The method of claim 1, further comprising moving said electric field synchronically with said motion of said at least one dispensing element.

6. The method of claim 1, wherein said motion of said at least one dispensing element is selected so as to establish a spiral motion of said jet of said polymer fibers about the object, said spiral motion being characterized by a gradually deceasing radius.

7. The method of claim 1, further comprising translationally moving the object relative to said jet of said polymer fibers so as to uniformly distribute said polymer fibers onto the object.

8. The method of claim 7, wherein said translational motion of the object is a reciprocation motion.

9. The method of claim 7, wherein said translational motion of the object is an harmonic motion.

10. The method of claim 1, wherein the object has a tubular shape.

11. The method of claim 1, wherein the object is an expandable tubular supporting element.

12. The method of claim 11, wherein said expandable tubular supporting element comprises a deformable mesh of metal wires.

13. The method of claim 11, wherein said expandable tubular supporting element comprises a deformable mesh of stainless steel wires.

14. The method of claim 1, wherein the object is a stent.

15. The method of claim 1, wherein the object is a stent assembly having at least one coat.

16. The method of claim 1, wherein the object is a stent mounted on a stent delivery system.

17. The method of claim 1, wherein the object is an implantable medical device.

18. The method of claim 1, wherein the object is an implantable medical device mounted on a stent delivery system.

19. The method of claim 1, wherein a medicament is mixed with said charged liquefied polymer and is eo-dispensed therewith through said at least one dispensing element; so as to coat the object with an electrospun medicated coat.

20. The method of claim 19, wherein said medicament is dissolved in said charged liquefied polymer.

21. The method of claim 19, wherein said medicament is suspended in said charged liquefied polymer.

22. The method of claim 19, wherein said medicament is constituted by particles embedded in said polymer fibers.

23. The method of claim 19, wherein said medicament is heparin.

24. The method of claim 19, wherein said medicament is a radioactive compound.

25. The method of claim 19, wherein said medicament is silver sulfadiazine.

26. The method of claim 1, further comprising constituting a mendicant into compact objects and distributing said compact objects between said polymer fibers.

27. The method of claim 26, wherein said medicament is heparin.

28. The method of claim 26, wherein said medicament is a radioactive compound.

29. The method of claim 26, wherein said medicament is silver sulfadiazine.

30. The method of claim 26, wherein said compact objects are capsules.

31. The method of claim 26, wherein said compact objects are in a powder form.

32. The method of claim 26, wherein said distributing of said compact objects is by spraying.

33. The method of claim 11, further comprising mounting said expandable tubular supporting element onto a mandrel, prior to said dispensation of said charged liquefied polymer.

34. The method of claim 33, further comprising dispensing said charged liquefied polymer through said at least one dispensing element within said electric field, and moving said dispensing element relative to said mandrel so as to coat said mandrel, hence providing an inner coat to said expandable tubular supporting element.

35. The method of claim 11, further comprising providing at least one adhesion layer onto said expandable tubular supporting element.

36. The method of claim 35, wherein said at least one adhesion layer is an impervious adhesion layer.

37. The method of claim 36, wherein said at least one adhesion layer is an impervious adhesion layer.

38. The method of claim 1, further comprising providing at least one additional coat on the electrospun coat.

39. An apparatus for coating a non-rotary object with an electrospun coat, the apparatus comprising at least one dispensing element being at a potential difference relative to the object, said at least one dispensing element being capable of moving relative to said object while dispensing a charged liquefied polymer within an electric field defined by said potential difference, so as to form a jet of polymer fibers having a sufficient transverse velocity relative to an axis defined by said dispensing element and the object, thereby coating the object.

40. The apparatus of claim 39, wherein said at least one dispensing element is capable of moving along a helix path.

41. The apparatus of claim 39, wherein said at least one dispensing element is capable of moving along a circular path.

42. The apparatus of claim 39, wherein said at least one dispensing element is capable of moving along a zigzag path.

43. The apparatus of claim 39, wherein said at least one dispensing element is designed and constructed such that said electric field moves synchronically with said motion of said at least one dispensing element.

44. The apparatus of claim 39, wherein said motion of said at least one dispensing element is selected so as to establish a spiral motion of said jet of said polymer fibers about the object, said spiral motion being characterized by a gradually deceasing radius.

45. The apparatus of claim 39, wherein said at least one dispensing element comprises an arrangement of electrodes.

46. The apparatus of claim 39, wherein said at least one dispensing element comprises a rotatable ring having at least one capillary.

47. The apparatus of claim 45, wherein said rotatable ring is made of a dielectric material.

48. The apparatus of claim 45, wherein said rotatable ring is made of a conductive material.

49. The apparatus of claim 39, further comprising a bath for holding a liquefied polymer, said bath being in fluid communication with said at least one dispensing element.

50. The apparatus of claim 49, further comprising a pump for transferring said liquefied polymer from said bath to said at least one dispensing element.

51. The apparatus of claim 39, further comprising a mechanism for translationally moving the object relative to said jet of said polymer fibers so as to uniformly distribute said polymer fibers onto the object.

52. The apparatus of claim 51, wherein said translational motion of the object is a reciprocation motion.

53. The apparatus of claim 51, wherein said translational motive of the object is an harmonic motion.

54. The apparatus of claim 39, further comprising said charged liquefied polymer and further wherein a medicament is mired with said charged liquefied polymer and is co-dispensed therewith through said at least one dispensing element, so as to coat the object with an electrospun medicated coat.

55. The apparatus of claim 54, wherein said medicament is dissolved in said charged liquefied polymer.

56. The apparatus of claim 54, wherein said medicament is suspended in said charged liquefied polymer.

57. The apparatus of claim 54, wherein said medicament is constituted by particles embedded in said polymer fibers.

58. The apparatus of claim 54, wherein said medicament is heparin.

59. The apparatus of claim 54, wherein said, medicament is a radioactive compound.

60. The apparatus of claim 54, wherein said medicament is silver sulfadiazine.

61. The apparatus of claim 39, further comprising a sprayer for distributing compact objects constituting a mendicant therein between said polymer fibers.

62. The apparatus of claim 61, wherein said medicament is heparin.

63. The apparatus of claim 61, wherein said medicament is a radioactive compound.

64. The apparatus of claim 61, wherein said medicament is silver sulfadiazine.

65. The apparatus of claim 61, wherein said compact objects are capsules.

66. The apparatus of claim 61, wherein said compact objects are in a powder form,

67. A method of treating a constricted blood vessel, the method comprising:
(a) providing a stent assembly;
(b) dispensing a charged liquefied polymer through at least one dispensing element within an electric field to thereby form a jet of polymer fibers, and moving said dispensing element relative to said stent assembly to provide said polymer fibers with a sufficient transverse velocity relative to an axis defined by said dispensing element and said stent assembly, so as to coat said stent assembly with an electrospun coat; and (c) placing said stent assembly in the constricted blood vessel.

68. The method of claim 67, further comprising expanding said stent assembly so as to dilate tissues surrounding said stem assembly in a manner such that flow constriction is substantially eradicated.

69. The method of claim 67, wherein said moving said at least one dispensing element is, at least in part, in a helix path.

70. The method of claim 67, wherein said moving said at least one dispensing element is, at least in part, in a circular path.

71. The method of claim 67, wherein said moving said at least one dispensing element is, at least in part, in a zigzag path.

72. The method of claim 67, further comprising moving said electric field synchronically with said motion of said at least one dispensing element.

73. The method of claim 67, wherein said motion of said at least one dispensing element is selected so as to establish a spiral motion of said jet of said polymer fibers about said stent assembly, said spiral motion being characterized by a gradually deceasing radius.

74. The method of claim 67, further comprising translationally moving said scent assembly relative to said jet of said polymer fibers so as to uniformly distribute said polymer fibers onto said stent assembly.

75. The method of claim 74, wherein said translational motion of said stent assembly is a reciprocation motion.

76. The method of claim 74, wherein said translational motion of said stent assembly is an harmonic motion.

77. The method of claim, 67, wherein said stent assembly is mounted on a stent delivery system.

78. The method of claim 67, wherein a medicament is mixed with said charged liquefied polymer and is co-dispensed therewith through said at least one dispensing element, so as to coat the object with an electrospun medicated coat.

79. The method of claim 78, wherein said medicament is dissolved in said charged liquefied polymer.

80. The method of claim 78, wherein said medicament is suspended in, said charged liquefied polymer.

81. The method of claim 78, wherein said medicament is constituted by particles embedded in said polymer fibers,

82. The method of claim 78, wherein said medicament is heparin.

83. The method of claim 78, wherein said medicament is a radioactive compound.

84. The method of claim 78, wherein said medicament is silver sulfadiazine.

85. The method of claim 67, further comprising constituting a mendicant into compact objects and distributing said compact objects between said polymer fibers.

86. The method of claim 85, wherein said medicament is heparin.

87. The method of claim 85, wherein said medicament is a radioactive compound.

88. The method of claim 85, wherein said medicament is silver sulfadiazine.

89. The method of claim 85, wherein said compact objects are capsules.

90. The method of claim 85, wherein said compact objects are in a powder form.

91. The method of claim 85, wherein said distributing of said compact objects is by spraying.

92. The method of claim 67, further comprising providing at least one additional coat on said electrospun coat.