Method of Forming Prefabricated Units Used in the Production of Systems of Prosthetic Aortic Valve Transcatheter Implantation and a Prosthetic Aortic Valve Prefabricated Unit

Abstract

A method of forming prefabricated units used in production of systems of prosthetic aortic valve transcatheter implantation and prosthetic aortic valve prefabricated unit with an non-thrombogenic smooth surface layer or with a porous fibrous layer constituting a scaffold for epithelium cell culture, intended for manufacturing TAVI system. Stents for covering and solutions of polycarbonate silicones and/or polycarbonate urethanes and/or polyurethane with average molecular weight in the range from 50,000 g/mol to 200,000 g/mol in the solvent DMAC are prepared. Initially a smooth layer of polycarbonate silicone is applied in the electrospinning machine by electro spraying with use of the solution in DMAC with the concentration of 2-8% w/w. and/or a fiber of polycarbonate urethane is applied by electrospinning on the roller with use of the solution in DMAC with the concentration of 8-20% w/w to obtain the first surface layer, with a specified speed, number of heads, thickness of capillaries, speed of movement, voltage and distance between the capillary and the roller and the specified flow of the solution on the feeding pump and after a certain time the layer covering the roller with thickness of 1-100 m is obtained. Thereafter the inner intermediate layer of polycarbonate silicone is formed by electro spraying. When the thickness of the layer is approximately 5 to 100 m the process is stopped and stents are placed on the formed layer and similarly like applying the former intermediate layer the application of the inner intermediate layer is continued on the whole length of the roller. Thereafter the final surface layer is applied like the first surface layer until a prefabricated unit with the polymer material thickness from 50 to 250 m is obtained.

Claims

1. A method of forming prefabricated units used in production of systems of prosthetic aortic valve transcatheter implantation with a non-thrombogenic smooth surface layer or with a porous fibrous layer constituting a scaffold for epithelium cell culture, intended for manufacturing TAVI system in form of a material made of nanofiber integrated with a stent, comprising: preparing between 1 and 133 stents made of a cobalt-nickel alloy with a wall thickness of 150-500 m providing a first solution in a solvent DMAC, providing an electrospinning machine electrospraying a smooth layer of polycarbonate silicone is applied with use of the solution in DMAC with a concentration of 2-11% w/w. and/or by electrospinning polycarbonate urethane fiber is applied with use of the solution in DMAC with concentration of 8-20% w/w. onto a roller to obtain a first surface layer, applying specified speed, number of heads, thickness of capillaries, rotation speed, voltage and distance between each capillary and the roller, whereas flow on a pump administering the solution on the heads forms a layer covering the roller with thickness of approximately 1-100 m thereafter forming an inner intermediate layer by electrospraying the layer of polycarbonate silicone with use of the solution in DMAC with a concentration of 2-8%/w. and/or by electrospinning the polycarbonate urethane silicone with use of the solution in DMAC with the concentration of 8-20%/w. applying specified speed, number of heads, thickness of capillaries, rotation speed, voltage and distance between each capillary and the roller, and when the thickness of the layer is approximately 5 to 100 m, the forming is stopped, and placing the stents onto the formed layer, positioning their location so that the distance between each of them was 30 mm, and similarly to applying the inner intermediate layer, applying the inner intermediate layer on entire length of the roller, obtaining the thickness of approximately 5 to 100 m, thereafter a final surface layer is applied similarly to the first surface layer until prefabricated units of a polymer material thickness of 50 to 250 m is obtained.

2. The method of claim 1 wherein said first solution comprises solutions of polycarbonate silicones and/or polycarbonate urethanes and/or polyurethane with average molecular weight in range from 5000 g/mol to 200 000 g/mol.

3. The method of claim 1 wherein speed of the roller rotation is between 100 to 6000 rpm.

4. The method of claim 1, wherein the electrospinning machine is equipped with a head and/or a multi-head equipped with capillaries with the thickness of 21-28 G in an amount of 1 to 100.

5. The method of claim 1, wherein the electrospinning machine head is fitted on a shoulder which moves cyclically at the speed of 40 mm/s along the roller foe a prefabricated unit with a constant material thickness and/or with a stationary shoulder for prefabricated units with gradient thinning of material cross-section.

6. The method of claim 1, wherein a gradient of difference in the material thickness with gradient thinning of polymer material cross-section is 10 m for each centimeter of a longitudinal dimension of the material.

7. The method of claim 1, wherein the voltage between each capillary and the roller was applied in range of 5 kV-50 kV, maintaining the distance between them from 30 to 500 mm.

8. The method of claim 1, further comprising a steel roller with a diameter in a range of from 19 mm to 25 mm and with a length of from 50 mm to 6000 mm and with a polished surface with surface roughness of 14.

9. A prefabricated unit used in production of systems of prosthetic aortic valve transcatheter implantation with a non-throbogenic smooth surface layer or with a porous fibrous layer constituting a scaffold for epithelium cell culture, intended for manufacturing TAVI system in form of a material made of nanofiber integrated with a stent, comprising: a first surface layer, formed by electrospraying or electrospinning; an inner intermediate layer with thickness from 5 to 100 m made of the first surface material is applied; and in this surface stents made of cobalt-nickel and of tubular openwork design with an outer diameter from 20-26 mm and with a length from 10-40 mm are located; wherein the inner intermediate surface is covered by a final surface layer with thickness 1-100 m made of the material of the first surface layer, obtaining a prefabricated unit of a prosthetic heart valve with a polymer material thickness from 50 to 250 m.

10. The prefabricated unit of claim 9 wherein the first surface layer comprises polycarbonate silicone and/or polycarbonate urethane and/or polyurethane with average molecular weight from 50 000 g/mol to 200000 g/mol with thickness of 1-100 m.

11. The prefabricated unit of claim 9 wherein a cross-section of the polymer material is thinned with a thickness difference gradient of 10 m for each centimeter of a longitudinal dimension of the material.

Description

BRIEF DESCRIPTION OF THE DRAWING

[0011] Embodiments disclosed herein will be more fully understood from the following detailed description taken in connection with the accompanying drawings, which form a part of this application, and in which:

[0012] FIG. 1 illustrates a flow diagram of an embodiment of the present disclosure.

DETAILED DESCRIPTION

[0013] The invention relates to the method of one-stage manufacturing of the prosthetic heart valve and the sealing, with simultaneous fitting of these elements on the stent, which simplifies the currently used technology of production TAVI systems, at the same time improving their reliability. Nowadays, the technological solutions used to produce a prosthetic heart valve for TAVI systems involve the stage of connecting individual elements of the system, most commonly by sewing. Such operation requires high precision from people who manually sew leaflets and connect the sealing with the stent. Undoubtedly, it is a significant drawback, taking into consideration the effort and time required for this operation. Moreover, there is a high probability of occurrence of product defects and a high probability of occurrence of a human mistake. There is also a likelihood of damage to the sealing material and leaflets. It is a very costly stage of the production process due to the manual work involved on the one hand and due to a very detailed quality control of the manufactured products after this operation on the other hand.

[0014] The invention relates to the manner that is characterized by the fact that multilayer materials are manufactured by electrospinning in the form of a polymer cuff permanently integrated with the stent. The prefabricated unit that is produced allows to simplify and reduce the range of manual work during the final stage of valve leaflets forming. Additionally, a seamless connection of the stent with nanofiber with the continuous layer reduces the final profile of the guiding system, thanks to which a catheter with a smaller diameter may be used. Use in the process of manufacturing TAVI system of a prefabricated unit made of biocompatible, hemocompatible, stable polymers, favorably from the group of aromatic polycarbonate urethanes and polycarbonate silicones with a layer nanofiber, placed seamlessly on the stent formed according to the invention description, allows obtaining the material which is hemocompatible, dimensionally stable, with high flexibility and improved fatigue resistance (sensitive points which weaken the construction of such implant are the places of sewing, where disintegration of fiber appears).

[0015] The invention relates to the method which is characterized by the fact that the polymer or the polymer mixture from the group of biocompatible, hemocompatible, and biostable polymers, favorably from the group of aromatic polyurethanes, polycarbonate urethanes and polycarbonate silicones with average molecular weight in the range from 50 000 g/mol to 200 000 g/mol favourably 130 000 g/mol is dissolved in a solvent favorably with low vapor pressure, favorably NN-dimethylacetamide (DMAC) or NN-dimethyloformamide (DMF). The concentrations of solutions used in this method during forming the fiber from 1% (w/w) to 20% w/w, favorably 18% by weight. In the case of forming outer monolithic layers by electrospraying, the concentration of the solution is lower by 10% than the concentration from which the fibres are formed. The cuff integrated with the stent is formed in the chamber of the electrospinning machine on the roller with a diameter of 18 mm to 30 mm, the size ultimately connected with the valve diameter, while the roller diameter should be smaller by 1 mm in comparison to the nominal valve diameter. The beneficial roller diameter22 mm in case of the ultimate valve diameter 23 mm. In the variant of obtaining the material with constant thickness, the shoulder of the electrospraying and/or electrospinning head is movable. The speed of movement from 10 to 100 mm/s is favorably 40 mm/s; however, when the thickness gradient of the material on the length of the pre-fabricated unit is of importance, the head is fitted at a right angle over the place of the stent mounting. Due to the diversity of the surface layers structure of the fiber forming the cuff, which are responsible for biocompatibility and non-thrombogenicity of the material, whose thickness and morphology are shaped by the selection of ingredients and by the operating concentration of the solutions of polycarbonate urethane (table 2) or polycarbonate silicone (table 3), as well as the changes of processing parameters used in electrospinning. The invention involves two solutions. The first solution (Table 1) consists in leaving the final surface layer in the form of nanofibers, which can constitute the scaffold on which the endothelial cells deposit. In the other solution, the final surface layer is shaped in a smooth and impermeable form. The formed tight and smooth layer with a regulated process of thickness from 3 to 50 m favorably 4.6 m minimizes the impact of the cuff surface with blood cells lowers the thrombogenity of this material. In both solutions, during electrospinning, a collector in the form of a roller with the length dependent on the stent is used. The roller should be at least 2.5 times longer than the stent length. After high-gloss polishing, a polymer material is applied. The material constitutes the final layer favorably with the thickness not exceeding 3% of the optimal leaflet thickness (beneficial thickness of leaflets 100-200 m) on the length minimally 50 mm in case of the stent for consolidation not longer than 20 mm. Applied solutions, favorably the solutions of polycarbonate silicones with an average molecular weight of 70 000 g/mol in DMAC and/or the solutions of polycarbonate urethanes with an average molecular weight of 200 000 g/mol in DMAC (Mw=200000) in DMAC. Another layer is applied with the use of one head for one type of morphology or with the use of a double head (a head for electrospraying and a head for electrospinning) powered by two solutions, which allows for obtaining a mixed morphology. Respectively, the concentrations of polycarbonate urethanes (Mw=200000) for electrospraying are in the range of 1% w/w to 11% w/w favorably 5% w/w, while the concentrations of solutions for electrospinning are in the range from 10% w/w to 20% w/w favorably 18% w/w (depending on the molecular weight of the applied polymer). Favorably, this layer does not exceed 40% of the thickness of the whole cross-section of the material layer. After finishing this stage, the applied polymer layer on the roller will obtain a thickness from 10 to 60 m favorably 57 m; the metal stent is put onto the roller covered by the layer of formed composite, favorably made of chromo-cobalt alloy or nitinol, of open-work structure which allows to tighten it on the catheter thereafter. The stent is positioned so that to obtain the minimal total length of the cuff 2.5 the length of the valve stentFIG. 1 Another layer is the continuation of the former layer, which is applied by electrospinning (the solution of polycarbonate urethanes is in the range of the concentration from 10% w/w to 20% w/w favorably 18%) and/or electrospraying (the solution of polycarbonate urethanes in the range of the concentration from 1% w/w to 11% w/w favorably 8%) or electrospinning with simultaneous electrospraying (solution parameters). This manner allows the material to increase desired flexibility and increase the durability of the stent consolidation. The composite layer which is formed this way should have a thickness in the range from 40 m to 195 m, favorably 141 m. The final stage of forming the prefabricated unit is forming the outer layer, similar to the described above operation of creating the surface layer.

TABLE-US-00001 TABLE 1 Example of the material obtained according to the invention - solution no 1 Layer Material and structure of the layer Notes 1 aromatic polycarbonate urethane 1 Inner layer, applied (fibres) + aromatic directly on the roller Polycarbonate urethane 2 (electrospraying) 2 aromatic polycarbonate urethane 1 (electrospraying) 3 aromatic polycarbonate urethane 1 Layer of the same (fibres) + aromatic composition as the Polycarbonate 2 (electrospraying) first one

TABLE-US-00002 TABLE 2 Example of the material obtained according to the invention - solution no 2A Layer Material and structure of the layer Notes 1 aromatic polycarbonate urethane 2 Inner layer, applied directly on (electrospraying) the roller 2 aromatic polycarbonate urethane 1 Layer applied on the bearing (electrospraying) element of the valve (steel stent) - increasing the adhesion of next layers 3 Aromatic polycarbonate urethane 1 Layer of the same composition (fibres) + aromatic polycarbonate as the first one 2 (electrospraying) 4 aromatic polycarbonate urethane 1 Outer layer - smoothing the (electrospraying surface of the material

TABLE-US-00003 TABLE 3 Example of the material obtained according to the invention - solution no 28 Layer Material and structure of the layer Notes 1 polycarbonate silicone (electrospraying) Inner layer, applied directly on the roller 2 aromatic polycarbonate urethane 1 (fibres): aromatic polycarbonate urethane 2 (electrospraying) 3 aromatic polycarbonate urethane 1 Layer increasing the (electrospraying) adhesion of next layers 4 aromatic polycarbonate urethane 1 Layer of the same (fibres): aromatic polycarbonate urethane composition as point 2 2 (electrospraying) 5 polycarbonate silicone (electrospraying) Outer finishing layer - smoothing the surface of the material

[0016] The invention relates to the method that guarantees repeatability of dimensions and mechanical parameters of the obtained prefabricated unit. provided that the constant temperature of manufacturing is maintained, favorably in the range of 16-22 C. and humidity favorably in the range of 50-60%. The choice of concentrations of polymer solutions used in the process of electrospinning and electrospraying (favorably not higher than 20% w/w) flows (favorably in the range of 0.5 to 2 ml/h) voltage (favorably to 40 kV) and the distance between electrodes (favorably in the range between 15-24 cm) depending on the molecular weight of a used polymer or the mixture of polymers. The dispersion of the fibers diameter and the quality of control of the fiber is specified with the use of the technique of electron scanning microscopy.

[0017] The invention is presented in the examples of executions shown below and in the picture which illustrates the profile of the longitudinal section of the valve prefabricated unit consistent with the method of its manufacturing. A prefabricated unit is used in the production of systems of prosthetic aortic valve transcatheter implantation consisting of: A) a stent integrated with the polymer material, B) a surface polymer layer favorably with the thickness of 1-100 m. C) an inner intermediate polymer layer favorably with a thickness of 5-100 man in this layer, the stent A is molded, D) the surface layer favorably with a thickness of 1-100 m, F) the length of the stent

Example I

[0018] In order to obtain simultaneously five prefabricated units with athrombogenic smooth surface layer for manufacturing TAVI system in the form of a cuff made of nano-fibre integrated with a stent the following items were prepared: 5 stents made of the cobalt-nickel alloy with the wall thickness of 250 m and of a tubular open-work structure with the outer diameter of 23 mm and the length of 18 mm, and solutions of polycarbonate silicone with average molecular weight of approximately 50 000 g/mol in DMAC, and solutions of polycarbonate urethanes with average molecular weight of approximately 200 000 g/mol in DMAC.

[0019] A steel roller with the diameter of 22 mm and with the length of 300 mm, with polished surface (surface roughness14) was fitted in the electrospinning machine. The process of electrospinning was carried out in the humidity conditions of 40% and in the temperature of 16 C. At the beginning a surface layer made of polycarbonate silicone was applied on the roller by electrospraying with use of the solution in DMAC with the concentration of 2% w/w. The speed of the roller rotation was 250 rpm, a head equipped with one 23 G capillary (size in G scaleGauge) was fitted on the shoulder which cyclically moved at the speed of 40 mm/s along the roller. The difference in the potentials applied at the capillary and at the collector was 5 kV, and there was a distance between the capillary and the collector of 220 mm. The flow volume was established at 1 ml/h. After 2 hours the layer covering the roller with the thickness of approximately 4.6 m and the length of 270 mm was obtained. Thereafter the inner intermediate layer was being formed with use of two heads simultaneouslyone equipped with five capillaries 21 G for electrospinning and the other equipped with one capillary 21 G for electrospraying, with use of the polycarbonate urethane solution with the concentration of 18% w/w on head 1 and the polycarbonate urethane solution with the concentration of 11% on head 2. The former parameters were retained, the speed of the roller rotation250 rpm, the speed of the shoulder40 mm/s and the voltage between the capillary and the roller37 kV, the distance capillarycollector 220 mm. The flow on the pump feeding the polycarbonate urethane solution with the concentration of 18% w/w on head 1 was set in the amount of approximately 1 ml/h, and the polycarbonate urethane solution with the concentration of 11% w/w fed on head 2 in the amount of 0.1 ml/h. After the period of 7 h, when the thickness of the layer was approximately 57 m the process was stopped in order to put 5 stents on the formed layer, positioning their location so that the distance between each of them was 30 mm. Then the operation of putting the outer intermediate layer on the whole length of the roller was continued with the flow decreased down to 0.5 ml/h and with other parameters retained. After the next 22 h manufacturing of the inner intermediate layer was finished, with the obtained thickness of approximately 83.8 m. Afterwards the procedure of manufacturing the final surface layer was launched, with use of polycarbonate urethane solution in DMAC with the concentration of 5% weight by weight, the flow on the pump 1.5 ml/h and the head with one capillary, the other parameters of manufacturing remained unchanged. After 2 h the production process is finished with the removal of the manufactured products from the roller. The final products in the form of five prefabricated units with the polymer material thickness of 150 m prepared for further simple processing in order to obtain a ready TAVI system were obtained, by dragging a formed cuff through the stent, and then cutting and sewing the valve leaflets and crimping the whole construction on the catheter.

Example II

[0020] In order to obtain simultaneously five prefabricated units with a thrombogenic smooth surface layer for manufacturing TAVI system in the form of a cuff made of nanofiber integrated with a stent, the following items were prepared: 5 stents made of the cobalt-nickel alloy with the wall thickness of 500 m and of a tubular open-work design with the outer diameter of 23 mm and the length of 18 mm, and solutions of polycarbonate urethanes with average molecular weight of approximately 50 000 g/mol in DMAC.

[0021] A steel roller with a diameter of 22 mm and with a length of 300 mm, with a polished surface (surface roughness14) was fitted in the electrospinning machine. The process of electrospinning was carried out in the humidity conditions of 60% and at the temperature of 22 C. At the beginning, a surface layer made of polycarbonate urethane was applied on the roller by electrospraying with use of the solution in DMAC with the concentration of 8% w/w. The speed of the roller rotation was 250 rpm, a head equipped with one 23 G capillary was fitted on the shoulder which cyclically moved at the speed of 40 mm/s along the roller. The difference in the potentials applied at the capillary and at the collector was 37 kV, and there was a distance between the capillary and the collector of 220 mm. The flow volume was established at 1 ml/h. After 1.5 hours the layer covering the roller with a thickness of approximately 4.6 m and the length of 270 mm was obtained. Afterward the inner intermediate layer was formed with the use of two heads simultaneouslyone equipped with five capillaries 21 G for electrospinning and the other equipped with one capillary 21 G for electrospraying, with the use of the polycarbonate urethane solution with the concentration of 18% w/w on head 1 and the polycarbonate urethane solution with the concentration of 11% on head 2. The former parameters were retained: the speed of the roller rotation250 rpm, the speed of the shoulder40 mm/s and the difference of potentials the capillary and the collector37 kV, the distance capillarycollector 220 mm. The speed of administering the polycarbonate urethane solution with the concentration of 18% w/w through head 1 was set in the amount of approximately 1 ml/h, and the polycarbonate urethane solution with the concentration of 11% w/w fed through head 2 in the amount of 0.1 ml/h. After the period of 7 h, when the thickness of the layer was approximately 57 m, the process was stopped in order to put 5 stents on the formed layer, positioning their location so that the distance between each of them was 30 mm. Then the operation of putting the outer intermediate layer on the whole length of the roller was continued with the flow decreased down to 0.5 ml/h and the other parameters retained. After the next 22 h manufacturing of the inner intermediate layer was finished, with the obtained thickness of approximately 83.8 m. Thereafter, the procedure of manufacturing the final surface layer was launched, with the use of polycarbonate urethane solution in DMAC with the concentration of 8% weight by weight, the flow on the pump 1.5 ml/h and the head with one capillary, the other parameters of manufacturing remained unchanged. After 1.5 h the production process was finished with the removal of the manufactured products from the roller. The final products in the form of five prefabricated units with the polymer material thickness of 150 m prepared for further simple processing in order to obtain a ready TAVI system were obtained by dragging a formed cuff through the stent, and then cutting and sewing the valve leaflets and crimping the whole construction on the catheter.

Example III

[0022] In order to obtain simultaneously five prefabricated units with a fiber surface layer enabling introduction of epithelial cells for manufacturing the TAVI system in the form of a cuff made of nanofiber integrated with a stent the following items were prepared: 5 stents made of the cobalt-nickel alloy with the wall thickness of 250 m and of a tubular open-work design with the outer diameter of 23 mm and the length of 18 mm, and solutions of polycarbonate urethanes with average molecular weight of approximately 200 000 g/mol in DMAC.

[0023] A steel roller with the diameter of 22 mm and with the length of 300 mm, with the polished surface (surface roughness14) was fitted in the electrospinning machine. The process of electrospinning was carried out in the humidity conditions of 50% and in the temperature of 19 C. At the beginning, a fiber layer was applied on the roller with use of two heads fitted simultaneously on the shoulder moving cyclically along the roller at the speed of 40 mm/s, one head equipped with five 28 G capillaries for electrospinning and the other equipped with one 21 G capillary for electrospraying, with use of the polycarbonate urethane solution with the concentration of 20% w/w on head 1 and the polycarbonate urethane solution with the concentration of 11% on head 2. The process of electrospinning was carried out with the following parameters: the speed of the roller rotation250 rpm, the difference in the potentials applied at the capillary and at the collector37 kV, and the distance between the capillary and the collector of 220 mm. The rate of the flow of polycarbonate urethane solution with the concentration of 18% w/w through head 1 was set in the amount of approximately 1 ml/h, and the polycarbonate urethane solution with the concentration of 11% w/w fed through head 2 in the amount of 0.1 ml/h. After the period of 7 h, when the thickness of the layer was approximately 57 m, the process was stopped. Thereafter an adhesive layer was applied by the method of electrospraying with use of polycarbonate urethane solution in DMAC with a concentration of 8% w/w; the speed of the roller rotation was 250 rpm, a head equipped with one 23 G capillary was fitted on the shoulder which cyclically moved at the speed of 40 mm/s along the roller. The difference in the potentials applied at the capillary and at the collector was 37 kV, and there was a distance between the capillary and the collector of 220 mm. The flow volume was established at 1 ml/h. After 3 hours, the process was stopped, and the film layer with a thickness of 9.2 m covering the roller with the length 270 mm was obtained. Thereafter five stents were put on the formed layer, positioning their location so that the distance between each of them was 30 mm. The flow was decreased down to 0.5 ml/h, and the other parameters were retained. The operation of putting the layer on the whole length of the roller was continued. After the next 22 h, manufacturing of the inner intermediate layer was finished, with the obtained thickness of approximately 83.8 m. The final products in the form of five prefabricated units with a polymer material thickness of 150 m prepared for further simple processing in order to obtain a ready TAVI system were obtained by dragging a formed cuff through the stent, and then cutting and sewing the valve leaflets and crimping the whole construction on the catheter.

Example IV

[0024] In order to obtain simultaneously five prefabricated units with a thrombogenic smooth surface layer for manufacturing TAVI system in the form of a cuff made of a nanofiber integrated with a stent, the following items were prepared: 5 stents made of the cobalt-nickel alloy with the wall thickness of 250 m and of a tubular open-work design with the outer diameter of 23 mm and the length of 18 mm, and solutions of polycarbonate urethanes with average molecular weight of approximately 200 000 g/mol in DMAC.

[0025] A steel roller with a diameter of 22 mm and with a length of 300 mm, with a polished surface (surface roughness14) was fitted in the electrospinning machine. The process of electrospinning was carried out in the humidity conditions of 50% and in the temperature of 19 C. At the beginning, a surface layer made of polycarbonate urethane was applied on the roller by electrospraying with the use of the solution in DMAC with a concentration of 8% w/w. The speed of the roller rotation was 250 rpm, a head equipped with one 23 G capillary was fitted on the shoulder which cyclically moved at the speed of 40 mm/s along the roller. The difference in the potentials applied at the capillary and at the collector50 kV, and there was a distance between the capillary and the collector of 220 mm. The flow volume was established at 1 ml/h. After 1.5 hours, the layer covering the roller with a thickness of approximately 4.6 m and the length of 270 mm was obtained. Thereafter the inner intermediate layer was being formed with use of two heads simultaneously. One equipped with five capillaries 21 G for electrospinning and the other equipped with one capillary 21 G for electrospraying, with the use of the polycarbonate urethane solution with the concentration of 18% w/w on head 1 and the polycarbonate urethane solution with the concentration of 11% w/w on head 2. The former parameters were retained, the speed of the roller rotation was 250 rpm, the speed of the shoulder was 40 mm/s, and the difference of potentials applied was 37 kV, the distance capillary-collector was 220 mm. The speed of feeding the polycarbonate urethane solution with the concentration of 18% w/w on head 1 was set in the amount of approximately 1 ml/h, and the polycarbonate urethane solution with the concentration of 11% w/w fed on head 2 in the amount of 0.1 ml/h. After the period of 7 h, when the thickness of the layer was approximately 57 m the process was stopped in order to put 5 stents on the formed layer, positioning their location so that the distance between each of them was 30 mm. Thereafter, the operation of putting the outer intermediate layer on the whole length of the roller was continued with the flow decreased down to 0.5 ml/h and with other parameters retained. After the next 35 h, the manufacturing of the inner intermediate layer was finished, with the obtained thickness of approximately 133.8 m. Thereafter, the procedure of manufacturing the final surface layer was launched, with the use of polycarbonate urethane solution in DMAC with the concentration of 8% w/w the flow on the pump 1.5 ml/h and the head with one capillary, the other parameters of manufacturing remained unchanged. After 1.5 h the production process was finished with the removal of the manufactured products from the roller. The final products in the form of five prefabricated units with the polymer material thickness of 200 m prepared for further simple processing in order to obtain a ready TAVI system were obtained, by dragging a formed cuff through the stent and then cutting and sewing the valve leaflets and crimping the whole construction on the catheter.

Example V

[0026] In order to obtain simultaneously five prefabricated units with a thrombogenic smooth surface layer for manufacturing TAVI system in the form of a cuff made of nanofiber integrated with a stent the following items were prepared: 5 stents made of the cobalt-nickel alloy with the wall thickness of 250 m and of a tubular open-work design with the outer diameter of 23 mm and the length of 18 mm, and solutions of polycarbonate silicone with average molecular weight of approximately 50 000 g/mol in DMAC, and solutions of polycarbonate urethanes with an average molecular weight of approximately 200 000 g/mol in DMAC.

[0027] A steel roller with a diameter of 22 mm and with a length of 300 mm, with a polished surface (surface roughness14) was fitted in the electrospinning machine. The process of electrospinning was carried out in the humidity conditions of 50% and in the temperature of 19 C. At the beginning, a surface layer made of polycarbonate silicone was applied on the roller by electrospraying with use of the solution in DMAC with the concentration of 8% w/w. The speed of the roller rotation was 250 rpm, a head equipped with one 23 G capillary was fitted on the shoulder which cyclically moved at the speed of 40 mm/s along the roller. The difference in the potentials applied was 37 kV, and there was a distance between the capillary and the collector of 220 mm. The flow volume was established at 1 ml/h. After 1.5 hours the layer covering the roller with the thickness of approximately 4.6 m and the length of 270 mm was obtained. Thereafter the inner intermediate layer was being formed with use of two heads simultaneously. One equipped with five capillaries 21 G for electrospinning and the other equipped with one capillary 21 G for electrospraying, with use of the polycarbonate urethane solution with the concentration of 18% w/w on head 1 and the polycarbonate urethane solution with the concentration of 11% on head 2. The former parameters were retained, the speed of the roller rotation250 rpm, the speed of the shoulder40 mm/s and the voltage between the capillary and the roller37 kV, the distance capillarycollector 220 mm. The flow on the pump feeding the polycarbonate urethane solution with the concentration of 18% w/w on head 1 was set in the amount of approximately 1 ml/h, and the polycarbonate urethane solution with the concentration of 11% w/w fed on head 2 in the amount of 0.1 ml/h. After the period of 1 h, when the thickness of the layer was approximately 7 m the process was stopped in order to put 5 stents on the formed layer, positioning their location so that the distance between each of them was 30 mm. The flow was decreased down to 0.5 ml/h. The other parameters retained. Thereafter the operation of putting the outer intermediate layer on the whole length of the roller was continued. After the next 13 h manufacturing of the inner intermediate layer was finished, with the obtained thickness of approximately 33 m. Thereafter the procedure of manufacturing the final surface layer was launched, with use of polycarbonate urethane solution in DMAC with the concentration of 8% w/w, the flow on the pump 1.5 ml/h and the head with one capillary. The other parameters of manufacturing remained unchanged. After 1.5 h the production process is finished with the removal of the manufactured products from the roller. The final products in the form of five prefabricated units with the polymer material thickness of 50 m prepared for further simple processing in order to obtain a ready TAVI system were obtained, by dragging a formed cuff through the stent, and then cutting and sewing the valve leaflets and crimping the whole construction on the catheter.

Example VI

[0028] In order to obtain simultaneously five prefabricated units with a thrombogenic smooth surface layer for manufacturing TAVI system in the form of a cuff made of nanofiber with the cross-section gradient change integrated with a stent the following items were prepared: 1 stent made of the cobalt-nickel alloy with the wall thickness of 250 m and of a tubular open-work design with the outer diameter of 23 mm and the length of 18 mm, and solutions of polycarbonate urethanes with average molecular weight of approximately 200 000 g/mol in DMAC.

[0029] A steel roller with the diameter of 22 mm and with the length of 100 mm, with the polished surface (surface roughness14) was fitted in the electrospinning machine. The process of electrospinning was carried out in the humidity conditions of 50% and in the temperature of 19 C. At the beginning a surface layer made of polycarbonate urethane was applied on the roller by electrospraying using the solution in DMAC with a concentration of 8% w/w. The speed of the roller rotation was 250 rpm, a head equipped with one 23 G capillary was fitted on the stationary shoulder in the place of mounting the stent on the further operations, the shoulders remained stationary till the end of manufacturing the prefabricated unit, the difference voltage between the capillary and the roller37 kV, and there was a distance between the capillary and the collector of 220 mm. The flow volume was established at 1 ml/h. After 30 min., the layer covering the roller with the thickness of approximately 4.6 m, in the place directly under the capillary, moving away from this place the measured thickness of a small extreme position on the roller the thickness approximately 3.4 m and the length 100 mm. Thereafter, the inner intermediate layer was being formed with the use of two heads simultaneously, one equipped with five capillaries 21 G for electrospinning and the other equipped with one capillary 21 G for electrospraying, with the use of the polycarbonate urethane solution with the concentration of 18% w/w on head 1 and the polycarbonate urethane solution with the concentration of 11% on head 2. The former parameters were retained, the speed of the roller rotation250 rpm, the shoulder with fitted heads remains stationary, and the voltage between the capillary and the roller50 kV, the distance capillarycollector 220 mm. The flow on the pump feeding the polycarbonate urethane solution with the concentration of 18% w/w on head 1 was set in the amount of approximately 1 ml/h, and the polycarbonate urethane solution with the concentration of 11% w/w fed on head 2 in the amount of 0.1 ml/h. After the period of 2.5 h, when the thickness of the layer was approximately 57 in the place directly under the capillary, moving away from this place, the measured thickness decreased; in the extreme position on the roller, the thickness was approximately 47 m. The process was ended in order to put 1 stent n the formed layer, positioning it perpendicularly under the capillaries. Thereafter, with the decreased flow down to 0.5 ml/h with the other parameters unchanged the operation of putting the inner intermediate layer on the whole length of the roller was continued. After the next 8.5 h, manufacturing of the inner intermediate layer was finished, with the obtained thickness of approximately 83.8 m in the place directly under the capillary; moving away from this place, the measured thickness decreases gradually down to approximately 62.2 m. Thereafter the procedure of manufacturing the final surface layer was launched, with use of polycarbonate urethane solution in DMAC with a concentration of 8% w/w, the flow on the pump 1.5 ml/h, and the head with one capillary. The other parameters of manufacturing remained unchanged. After 30 minutes, the production process is finished, with the manufactured products removed from the roller. The final product in the form of a prefabricated unita metal stent with attached nano-fiber with the thickness of polymer material of approximately 150 m, gradiently thinning to the final thickness of approximately 112.5 m prepared for further simple processing in order to obtain a ready TAVI by dragging a formed cuff through the stent, and then cutting and sewing the valve leaflets and crimping the whole construction on the catheter.