JP2005522594A - Covering process using electrospinning of very small peptides - Google Patents

Abstract

A versatile cover process has become possible through the identification and manipulation of multiple variables present in the electrospinning method of the present invention. By manipulating and controlling the various identified variables, electrospinning can be used to predictably produce thin materials with desired properties. The fibers produced by the electrospinning process have an average diameter of less than 100 micrometers. Appropriate manipulation of the identified variables is still wet when these fibers contact the target surface, thereby adhering to each other to form a cloth-like material and, if desired, adhere to the target surface. Ensure that the cover is formed on the lever. The particularly small size of these fibers, and the resulting gaps therebetween, provide an effective vehicle for drug and radiation delivery and form an effective membrane for use in fuel cells.

Description

(Background of the Invention)
The process of the present invention results in a versatile fabric and / or fabric-like cover and is particularly suitable for medical devices and industrial filtration applications. This cover can be made to have a wide range of desired characteristics, depending on the intended application. This process generally involves electrospinning technology.

  Electrospinning, or “electrospinning”, is a process for making fine polymer fibers using a charged solvent that is driven from a source to a target in an electric field. Using an electric field to attract a positively charged solution results in a jet of solution from the source container orifice to the grounded target. This jet forms a conical shape called the Taylor cone as it travels from the orifice. Typically, as the distance from the orifice increases, the cone extends to near the target, and the jet breaks into many fibers or extends diagonally before reaching the target. Also, before reaching the target, and depending on many variables, including target distance, charge, solution viscosity, temperature, solvent volatility, polymer flow rate, etc., the fiber begins to dry. These fibers are very thin and are typically measured in nanometers. The collection of these fibers against the target is very high in porosity and surface area, assuming that the solution is collected to ensure that the fibers are still wet enough to adhere to each other when reaching the target. As well as randomly oriented fiber materials with very small average pore sizes.

  FIG. 1 is a schematic diagram of basic components necessary for solvent electrospinning. The polymer is mixed with a solvent to form a solution 1 having the desired quality. This solution is filled into a syringe-like container 2 and fluidly connected to a blunt needle 3 that forms a spinneret 12. This needle 3 has a distal opening 4 through which the solution 1 is ejected by a controlled force 5 and is represented in a simplified manner supplied by a plunger 6. Any suitable controllable variable speed fluid placement system, which should be activated to ensure accurate flow rate.

  A significant potential difference 7 is established across the spinneret 12 and the receiving plate 8. The potential difference 7 assists the force 5 in stimulating the solution and by reducing the surface tension of the polymer solution 1 placed from the spinneret 3 to the receiving plate 8. The resultant force of the potential difference 7 and the placement force 5 creates an injection of the solution 9 and extends diagonally at a position 10 between the spinneret 3 and the receiving plate 8 due to the charge. The diagonally extending action produces a plurality of small strands or microfibers 11 which, depending on the volatility of the solvent, are dry even when they reach the plate 8. It does not have to be.

  Electrospinning was first introduced in US Pat. No. 1,975,504 (lighted on Anton Fonhals of Germany on Oct. 2, 1934). Formhals focused his efforts on using an electric field in combination with a movable spool collection device to provide a relatively parallel, silk-like strand supply. Subsequent efforts by Formhals (eg, as described in US Pat. No. 2,160,962) were directed to increasing the distance between the solution supply device and the collection electrode. As a result, the strands were completely dry when collected and therefore did not stick together.

  Electrospinning has not become a viable manufacturing method for decades after Formhals' efforts. This is because it is not possible to produce a sufficient amount of material, its production is inconsistent, low quality, and its technical need is insufficient to bring about significant process development. Recently, however, applications such as medical filters and device covers, as well as non-medical filtration applications, have led the applicant to further develop electrospinning processes.

  Electrospinning is currently the only way to create fibers with diameters measured in nanometers. To date, however, electrospinning as a manufacturing process has not been improved in that it can be used to produce repeatable fabrics that can be estimated by electrospinning. In addition, applications for electrospun fabrics, particularly medical applications, have not been defined and used to date.

(Summary of the Invention)
The present invention provides an electrospinning process that can be used to make a desired fabric having regularity. By manipulating the appropriate variables, the electrospun fabric achieves features that allow it to form a fabric that can adhere to an object (eg, a stent). As a result, the object is covered; or the fibers can be used to create independent fabric sheets or “skins” with various applications. FIG. 5 is a photograph of a stent covered with an electrospun fabric. In addition, the skin is extensible and directs the fibers of the coating in place. Arranging the fibers results in increased tensile strength, altered permeability, reduced bulk height, and reduced final part elongation (for the material, increased slope on the stress-strain curve). These extensibility features become very important when electrospun materials are used to cover the stent. When the covered stent is deployed and expanded, the membrane cover is easily stretched and subsequently increases the strength around the membrane. The electrospun material includes a plurality of randomly oriented, inter-tangled, non-woven fibers that have an average diameter of less than 100 micrometers.

  Accordingly, one aspect of the present invention provides a method for covering an object (eg, a stent) with a fibrous polymer layer. The stent is covered with a fibrous polymer layer by providing a spinneret charged with a potential difference to a predetermined location on the target plate. The stent is placed between the spinneret and a predetermined location on the target plate. The polymer is then forced through the spinneret, thereby transferring at least some of the potential difference to the polymer, so that the polymer is the target plate due to the potential difference between the liquid and the plate. Form a flow toward Before this flow reaches the plate, the flow extends obliquely into a plurality of nanofibers due to the potential difference between the liquid and the plate. At least some, preferably most, of the nanofibers strike the stent instead of reaching the target plate. This predetermined position on the target plate is then moved relative to the object until the entire object is covered. This is accomplished by moving the needle, electrically moving a point on the target plate where the potential difference is greatest relative to the needle, or moving the object itself, or a combination of these three techniques.

  Another aspect of the invention encompasses a method for producing a device comprising the device and an object (eg, a stent) coated with a fibrous polymer. Here, a clear distinction is made between covered and coated objects. Where particularly applicable to an object (eg, a stent) that defines multiple gaps, holes, or holes, a distinction is made based on how the polymer is distributed over the object. A polymer cover object, as used herein, is an object having a polymer that provides a somewhat continuous layer to cover substantially the entire outer surface of the object. The cover spans any gap or hole defined by the object. Thus, the covered stent includes a polymer layer that extends into the holes formed between the individual wires of the stent. FIG. 1 is an example of a covered stent.

  A polymer-coated object, as used herein, is one in which the individual films that make up the object have a layer of polymer bonded to the film. Thus, a coated stent is composed of a plurality of braided wires, each of which is coated with a polymer, but the gap between the wires remains open. There are applications where a coated stent is preferred over a cover stent. However, the manufacture of coated stents has heretofore been achieved by dip coating the stent in a liquid polymer and drying the stent. This is a problem for a number of reasons. It is difficult to dip coat very small stents. This is because the gaps between the individual wires are blocked by the polymer due to the surface tension of the polymer solution. The polymer also tends to adhere the individual wires of the stent together when dried. If the stent is later extended, the dried polymer coat will crack and chip, causing a potentially detrimental situation by the polymer chip entering the bloodstream.

  Thus, the coating method of the present invention begins with a cover object (preferably a stent) and heats the stent to a point where the fiber, preferably electrospun, loses the ability of the polymer to expand into the gap. The fibers extending into this gap break and are retracted to the nearest wire by surface tension. The individual wires of the stent are now coated. This coat is different from the coat of a dip coated stent. This is because, depending on the degree to which the stent is heated, this coat maintains a fibrous quality. This coat also typically only coats a portion of the periphery of the wire. Thus, the fibrous coat is resistant to cracking and the individual wires do not adhere together. Expansion of the coated stent of the present invention is similar to rubbing two pipe cleaners together, as opposed to separating them away from the two wires together.

  One aspect of the invention includes a method of delivering a drug to a target site using an electrospun fabric. Applications for electrospun fabrics with drug delivery capabilities include topical local delivery, antibiotic application, orthopedic application, cardiovascular application, gynecological application, hernia application, anti-adhesion application. There are four preferred methods of incorporating drug delivery with electrospinning technology: 1) mixing the drug and polymer, then spinning the mixture, 2) using two spinnerets to combine the polymer and drug Spinning separately and simultaneously, 3) impregnating the spun polymer with the drug, and 4) impregnating the spun polymer with the drug-containing microspheres.

  Using the first preferred method, the drug is mixed with the liquid polymer used in the spinning process. Electrospinning the resulting mixture yields a fabric containing the desired drug. This method may be particularly suitable for making unacceptable microfibers that are rejected by the body. In addition, the microfibers can be subsequently melted, compressed, or otherwise manipulated, thereby changing or eliminating interactions between the fibers without reducing the drug content of the microfibers. Can do.

  Using the second preferred method, two spinnerets are used proximal to each other, each of which has a common target. One spinneret is filled with polymer while the other is filled with drug solution. These spinnerets are charged and their solutions are spun simultaneously at a common target, creating a material containing polymer microfibers and drug microfibers. The drug supplied to the second spinneret can also be mixed with the second polymer to improve the spinning characteristics of the drug.

  The third method of drug delivery of the present invention involves impregnating a drug electrospun fabric. Some drugs may not be able to survive the electrospinning process. Taking advantage of the very small fiber size of the electrospun fabric and correspondingly the small size of the interaction between the fibers, the fabric can be impregnated with a liquid drug. Preferably, for example, polyester (eg, PET) spun to cover the scrim can be impregnated with rapamycin. When spinning PET, hexafluoro-iso-propanol (HFIP) (volatile material) is used to dissolve the PET in the solution. For example, impregnation with a dip coat, instead of mixing rapamycin and PET, PET spun with rapamycin before spinning prevents rapamycin from being destroyed by HFIP. Mixing a solution of rapamycin with PGA and PCL helps maintain rapamycin in the electrospun membrane.

  The delayed drug release effect can be obtained by impregnating the electrospun fabric containing the desired drug with microspheres. The microspheres further protect the drug from the manufacturing process and from evaporation. With the fourth method of drug delivery, microspheres containing this drug are trapped within the fabric gap and slowly dissolve in vivo to release the contained drug. An example of a polymer used to make a microsphere composite is a PCL membrane doped or filled with Alkermies in the form of PGA microspheres. The polymer is preferably spun over the scrim. Polymer selection is important because the polymer used in the spinning process defines drug release rate, material strength, stiffness, degradation time, and the like. Polymer selection also provides fabric elasticity. Polymers (eg polyurethane, PGA, PLA and PDO) produce crimped microfibers when spun. These crimped microfibers behave like nested springs, thereby giving the fabric an elastic quality. FIG. 6 is a photograph taken with an electron microscope of an electrospun fabric having elastic quality. Comparisons can be made to presentations 3-6, which are photographs of inelastic electrospun fabrics.

  The rate of drug release from the fabric depends on the difference in drug concentration between the fabric and the recipient tissue. As the drug is released, its concentration in the fabric decreases while the concentration in the recipient tissue increases and then gradually decreases as some of the drug is carried to the blood. Thus, the drug release rate is dynamic and can be summarized as “drug release kinetics”. “Drug release kinetics from drug-containing fabrics (eg, electrospun fabrics)” can be further controlled using non-drug-containing electrospun “covers”. This cover provides a barrier between the drug-containing fabric and the recipient tissue. If it has a smaller average microfiber size and smaller gaps than a drug-containing fabric, its cover allows the drug release to be limited to the desired rate, resulting in a low level of drug release over time. The cover can be made using the same or different polymer as the drug-containing polymer. Reference is made to FIGS. 7 and 8, which are micrographs of electrospun fabrics having relatively large microfibers (diameter of 5 micrometers in diameter) that can be used as drug-containing fabrics. Figures 9 and 10 are photomicrographs of electrospun fabrics having relatively small microfibers (1 micrometer in diameter) that can be used as non-drug-containing covers.

  A preferred application for the drug-containing fabric of the present invention relates to a method for preventing intimal hyperplasia. Intimal hyperplasia is a medical condition in which smooth muscle cells are applied to the site of injury within a blood vessel. Smooth muscle cells are delivered to the site to provide material for repair to the form of scar tissue. Intimal hyperplasia can be a dangerous condition. Because it causes partial or complete blood vessel blockage. It has been found that intimal hyperplasia can be reduced by applying an immunosuppressant to the site of injury. Traditional insight has shown that drugs are introduced inside blood vessels as close as possible to the site of injury. This has increasingly focused on the development of medicated stents and grafts in recent years. Drug-containing stents are an excellent mechanism for applying drugs directly to the vascular intima. A discussion of stents containing drugs used to prevent intimal hyperplasia can be found in Yang's published US Patent Application No. 20020143385A1, which is hereby incorporated by reference in its entirety. Can be found. A discussion of grafts designed to prevent intimal hyperplasia is discussed in US Pat. No. 6,440,166 to Kolluri, which is hereby incorporated by reference in its entirety. Kolliri focused on the luminal wall of the graft to prevent intimal hyperplasia.

  Surprisingly, drug-containing stents and grafts yielded results that were not better than expected when used to prevent intimal hyperplasia. Further studies have occasionally found that smooth muscle cells approach the target site by entering the vessel wall from the outside and moving through the wall in a radial direction relative to the damaged site. Thus, contact with the drug-containing stent is not made by all of the smooth muscle cells (ie, those smooth muscle cells that migrate to the inner surface of the intimal tissue). Thus, drug delivery mechanisms that allow smooth muscle cells to contact immunosuppressants before penetrating the vessel wall prevent intimal hyperplasia rather than stents containing drugs placed in the lumen of the vessel. It is more effective to do. The independent electrospun fabric of the present invention, impregnated with immunosuppressive agents, growth factors, cytokines or other therapeutic agents, is the optimal drug delivery vehicle for this application.

  The method of preventing intimal hyperplasia of the present invention is therefore a last step prior to closing an entry incision on the outer surface of a damaged or repaired vessel with a layer of electrospun fabric. Including the step of winding. The drug delivery wrap can be made from a degradable or non-degradable polymer. The wrap can be cut to size from a larger sample before incision. Preferably, the wrap is sized to overlap on either side of the target site and cover the target site completely in proportion to the degree of damage to be healed.

The invention also encompasses applications for the delivery of radiation to a patient. Radioactive materials are effective and difficult to handle and maintain safely. Furthermore, radioactive decay results in complex accumulation problems. The electrospun fabrics of the present invention can include non-radioactive materials that can later be “charged” with radiation. This material is introduced into the fabric either by mixing the material with a liquid polymer solution or by impregnating this material into the gaps of the formed electrospun fabric. This material is preferably ¹⁹⁶ thulium oxide (isotopic precursor), which becomes radioactive after being “charged” by exposure to radiation. When using a rechargeable material and waiting until just before the insertion charge, the material is typically produced, stored and handled without the cost and safety concerns associated with radioactive materials. Enable.

  Alternatively, materials such as calcium chloride or calcium phosphate can be similarly incorporated into the electrospinning process. These materials are characterized by attracting rather than storing radiation. Thus, when implanted, a medical device is created that acts as a radiation target. The device collects radiation at the desired location, thereby concentrating the radiation and at the same time protecting the surrounding tissue. The result is a more efficient use of radioactive energy. Smaller doses are used to achieve the result of a stronger beam that was previously required, a less focused beam that was unavoidably caused by collateral damage.

  Another aspect of the invention provides a process for making an electrospun material reinforced with a scrim. The scrim is placed in the spinning chamber of the electrospinning device and the polymer layer is electrospun directly onto the surface of the fabric scrim. This is advantageous because it incorporates the smaller fiber size of the electrospun material having the strength of a fabric scrim. Various techniques have been developed to improve the bond strength between the scrim and the spun membrane. This spun material can be “wet” spun directly onto the scrim fabric. These wet microfibers stick to the scrim. The scrim fabric can be precoated with a diluted mixture of spun polymers. This technique creates a sticky surface on which microfibers can be spun.

  Another aspect of the present invention provides a process for making an electrospun material that has been woven using a scrim. This process of weaving utilizes a wet, newly electrospun polymer by stamping or rolling the fabric into a polymer prior to curing the polymer. Alternatively, the fabric can be applied to the fabric by forming the fabric on a substrate (eg, a screen) that has been processed to weave. The weaving process increases the ability of the membrane to eject fluid, improves the flexibility of the material, allows the material to better drape, and reduces the stiffness of the material. This weaving processing process can be performed on the dry membrane by softening the membrane using either heat or a solvent.

  Yet another aspect of the invention provides a process for using an electrospun polymer layer as an adhesive to bond an already spun polymer cover to a target article or substrate. The wet polymer used is preferably the same as the already spun polymer cover. For this purpose, there are several advantages to using a wet electrospun polymer layer instead of an adhesive. First, the glue and fiber are the same, reducing the chances of bonding failure. Second, material requirements and material handling complexity are reduced. For example, most glues (eg, PMMA, cyanoacrylate, epoxide, etc.) are toxic. The use of these adhesives for medical applications significantly increases complexity and safety considerations. Third, no heat is required to bond the already spun material to the binding polymer layer. Adhesives often require heat, which can weaken the fibers. Fourth, using the same polymer as the binder used to make the fiber results in a device composed of fewer types of materials, potentially for medical products The control path can be shortened.

  Yet another aspect of the present invention is a process for electrospinning a composite material. Composite materials have more than one electrospun polymer and combine the different advantages of each polymer. This process can include mixing the polymers in one spinneret or using two spinnerets to simultaneously spin the material from each onto a common target.

  Yet another aspect of the invention provides a process for electrospinning a composite material that can be used in a fuel cell. Fuel cells operate by separating two electrolytes with a polymer membrane designed to pass certain charged atoms. This membrane is typically produced with a porosity of zero using a perfluorosulfonate ionomer (named Nafion®, sold by Dupont). In some cases, the membrane is reinforced with scrim fibers in the lamination process. Using the impregnation technique described above, the electrospun material is impregnated with a Nafion®-like material and has improved electrical conductivity, strength, durability, and most importantly reduced manufacturing costs. A membrane is produced.

  In addition, the surface area of the electrospun membrane affects the transport / cell efficiency. By using a bulk film containing Nafion®, the polymer surface area can be dramatically increased without causing a significant increase in film thickness. Also, as long as the cell has compartments with zero porosity, a membrane with a thickness that varies beyond the range of this membrane can be produced by manipulating the polymer flow rate, fiber size, temperature, or pressure. obtain.

  Preferably, the fuel cell is made by making a fiber solution for spinning using 100% Nafion® mixed with polyethylene oxide in a 10: 1 ratio. Alternatively, the composite material may be by spinning Nafion in one spinneret with PET, PP, PU from a second spinneret. In addition, Nafion® is spun directly on both sides of an open scrim cloth made of materials such as PET, PTFE, PP, or PEEK using heat and minimal pressure to produce the desired surface fabric or Bulk can be achieved.

(Detailed description of the invention)
(Mechanical setting of the electrospinning process of the present invention)
Referring now to FIG. 2, a preferred mechanical setting for the electrospinning process of the present invention is shown. Some components are similar to those in FIG. 1, but for clarity all components have been given new numbers. The electrospinning device 20 comprises a spinneret 22 on a spinning chamber 24, which is defined by a collecting plate 26 at its lower end. The spinneret 22 is installed in a carriage 28 of an xy translator 30, which is preferably an electrically controlled motion system. The xy translator 30 repositions the spinneret 22 anywhere in the spinning chamber 24 on the horizontal plate at the top of the chamber.

  The xy translator 30 includes an x motor 32 operably attached to a first belt 34 for translating the carriage 28 along a pair of first horizontal guide bars 36. The translator 30 is also operably attached to a second belt 40 for translating the carriage 28 along a pair of second horizontal guide bars 42 perpendicular to the first horizontal guide bar 36. In addition, a y motor 38 is provided.

  The spinneret 22 includes a syringe 43 and a needle 44. Needle 44 may be of various sizes, but for most applications it is optimally a 20 gauge needle. The spinneret is installed on the carriage assembly 28 using an adjustable bracket 46, which also serves as an electrical contact for a positive DC power source. The bracket 46 is configured and arranged to connect to the installation port 48 and be repositioned up and down the installation port 48, thereby providing height adjustment to the spinneret 22. The installation port 48 is also an insulator, isolating positive DC power from the rest of the device 20.

  The spinneret 22 is also connected to a positive DC power cable 50 and a pressure line 52. The power cable 50 provides the positive DC potential necessary to influence the electrospinning process. The pressure line 52 allows remote control of the syringe 43. The pressure line 52 carries fluid under pressure, and this fluid is used to apply a downward force to the plunger 54 of the syringe 43. This fluid is preferably compressed air or nitrogen, but can be any compressible or non-compressible fluid.

  Reference is now made to FIGS. Preferably, outside the spinning chamber 24, a power cable 50 and a pressure line 52 are connected to a power source 56 (FIG. 3) and a pump 58 (FIGS. 4a and 4b), respectively. The power supply 56 preferably provides a DC between 0 kV and 30 kV. A preferred pump 58a (shown in FIG. 4a) applies pressure to the syringe 43 through the coiled pressure line 52 using compressed air or nitrogen from a domestic source. An alternative pump 58b (shown in FIG. 4b) is a syringe pump (eg, made by Harvard Apparatus) and also functions to apply pressure to the syringe 43 through the coiled pressure line 52. To do. Both pumps 58 have adjustable feed rates.

  A computer (not shown) preferably communicates data flow with and controls both motors 32 and 38, power source 56 and pump 58. The computer executes various work-specific programs that provide optimal control over many of the variables inherent in the electrospinning process. A preferred controller program for the XY translator motors 32 and 38 is MD2, commercially available from Arick Robots of Hurst, Texas. Computer programs have been developed to control the pump and provide support for the MD2 program. However, this program is merely a memory device for storing parameters for a given desired fabric output and executing instructions entered just before the spinning process begins.

(Identified variables)
Various aspects of the invention are facilitated by the agile identification and manipulation of significant digits of variables. Understanding these variables, and the effect of these variables on the results of the electrospinning process, allows electrospinning to be used to make fiber materials having one or more of many desired properties. . The variables identified in the present invention include the following:
Polymer Type Polymer Viscosity Polymer Conductivity Potential Spinneret Size Distance to Collection Area Air Temperature / Humidity Polymer Feed Rate Relative Motion between Spinneret and Collection Area Pressure in Spin Chamber To Solubilize Polymer Chemicals used Polymer crystallinity.

  1. The type of polymer. A general requirement for the polymer used in the electrospinning process is that the polymer must flow and have unique properties for forming fibers. Polymers having these characteristics form a group from which individual selections can be made based on the intended purpose of the electrospun material.

  For example, it is often desirable that temporary medical devices used in vivo degrade over time and do not require removal surgery. Therefore, degradable polymers are selected for these applications. Degradable polymers suitable for electrospinning include: poly (L-lactide) (PLA), 75/25 poly (DL-lactide-co-E-caprolactone), 25/75 poly (DL-lactide-co-). E-caprolactone), poly (E-caprolactone) (PCL), collagen, polyactive, and polyglycolic acid (PGA). There are many acceptable volatile organic liquids that can be used to dissolve these polymers. Examples of these solvents include the following: hexafluoro-iso-propanol, dichloromethane, dimethylacetamide, chloroform, and dimethylformamide. The concentration of the solute relative to the solvent can have a dramatic effect on the final product. For example, lower solute concentrations can result in reduced production rates, smaller fiber diameters, lower permeability, and lower porosity for a given number / size spinneret.

  Other applications require materials that do not decompose. Non-degradable polymers acceptable for electrospinning include the following: polytetrafluoroethylene, polyurethane, polyester, polypropylene, polyethylene, and silicone. Also volatile organic liquids such as dimethylacetamide, methylene chloride, dimethylformamide, hexafluoro-iso-propanol (for polyurethane), hexafluoro-iso-propanol (for polyester), and 90 ° C. xylene (for polypropylene) Should be selected as the solvent.

  2. The viscosity of the polymer. Successful results are achieved using polymers with viscosities between 1 centipoise and 50 centipoise. In general, polymers with higher viscosities produce larger fibers.

  3. The conductivity of the polymer. By changing the conductivity of the polymer, the fiber size is changed in reverse. In other words, increasing the conductivity of the polymer reduces the resulting fiber size. The conductivity of the polymer can be changed by adding an ionic material (eg, a salt) to the polymer solution.

  4). potential. By increasing the potential between the spinneret and the receiving plate, the size of the electrospun fiber is reduced.

  5. The size of the spinneret. The spinneret size determines the size of the polymer stream exiting the spinneret needle. If this stream is too large, it will be distributed later or not at all for a given voltage level. Distributing slower or closer to the target results in water deposition on the target. The appearance of unacceptably large fibers also increases with the size of the spinneret. Conversely, if the spinneret needle is too small, the stream can be sprinkled too early and the fiber will dry as soon as it reaches the target.

  6). Distance to collection area. The distance to the collection area has the greatest effect on how wet the spun fiber is when it hits the target. If this distance is short, the fibers are still quite wet when they collide, increasing the degree to which they stick together and to the target. Thus, the needle can be lowered if it is desired to adhere the fibers to the substrate. Conversely, if it is desired to produce a thick, lofty material, the needle can be raised.

  7). Air temperature. As the air temperature increases, the needle height must be reduced to maintain similar fiber drying behavior. Reducing the temperature of the air in the spinning chamber reduces the drying rate of the fibers, and therefore tends to produce wetter fibers for a given spinneret height.

  8). Polymer feed rate. Increasing the polymer flow rate through the spinneret increases the height of the membrane, increases stiffness, reduces the ability of the material to resist delamination, and reduces membrane adhesion to other substrates. , And the ability to capture material in the membrane is reduced.

  9. Collection area movement. The relative movement between the spinneret and the collection area affects some of the properties of the resulting material. If the surface of the target to be covered moves under a spinneret that is stationary relative to the conductive plate (eg when the stent is rotated under a steady stream), the speed of rotation As the increases, the resulting material thickness decreases and the fibers that make up this material tend to be more aligned with each other. This can affect the strength, stiffness and porosity of the resulting material. As the needle moves relative to the conductive plate, thereby increasing the distance traveled by the polymer stream, the effect associated with changing the spinneret height appears.

  10. Pressure in the spinning chamber. Changing the atmospheric pressure in the spinning chamber affects the drying rate of the polymer being spun; lower pressures accelerate the drying process and higher pressures slow drying or solvent evaporation. Thus, if the fibers impinge on the target surface and the fibers are too dry or too wet, one way to adjust the drying rate is to adjust the spinning chamber pressure.

  11. The solvent used. More volatile solvents (ie, xylene, acetone, HFIP, and chloroform) tend to be more responsive to changes in spinning chamber pressure.

  12 Polymer crystallinity. Most polymers can be made rough to have lower crystallinity. The less crystalline polymer, as an amorphous region of the polymer, responds well to spinning chamber pressure changes and releases the solvent faster than the higher crystalline region. Thus, elevated pressure can be used for amorphous polymers to accurately produce slower drying and better microfiber bonding.

(Process for making drug delivery material)
A preferred method of using electrospinning techniques to make a material that facilitates drug elution when the material is placed in vivo is now described. A polymer-based solution (preferably a solution of polymer, solvent and immunosuppressant) is developed. Preferred polymers for the present application are 15-20% by weight, preferably 17.90% by weight poly DL-lactide (PLA), 80-85% by weight, preferably 82.10% by weight solvent (eg , HFIP). The preferred immunosuppressant is then added at 0.05% of the polymer mass. Preferred immunosuppressive agents include rapamycin, taxol, and warfin. This mixture is completely dissolved. Other acceptable polymers include, but are not limited to, polyester (PET), polyglycolide acid (PGA), polycaprolactone (PCL), polydioxanone (PDO), and polyurethane (PU). Preferably, when these other polymers are used, these polymers are used at 10-20 wt% with 80-90 wt% solvent (e.g. HFIP).

  A substrate (eg, a coarse mesh screen) is used as the target plate so that material can be removed from the plate without damage. This screen is very rough and allows drying and curing from both sides. Furthermore, the limited surface area of this screen can facilitate easy membrane release. However, to be a target plate, the substrate must be conductive so that it can be grounded. Grounding the substrate (eg, by connecting to a ground cable) is essential to establish a potential between the spinneret and the substrate. Stretchable materials (eg, screens) are preferred because when the substrate is stretched, the material separates from the substrate and is easily removed. In addition, an air flow can be drawn through the screen, which collects the spun polymer into a more discontinuous spinning pattern at locations where the polymer has a higher density. The motion controller and electrospinning device computer are then energized and a computer program for the motion controller is started. A preferred controller program is MD2, commercially available from Arick Robots of Hurst, Texas. Prior to running this program, a predetermined amount of solution (preferably 4.0 mL) is transferred into the spinneret. The piston is inserted into the bore of the spinneret barrel and the barrel assembly is inverted. The piston is then pushed until all the air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel. Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The system without the barrel is a manifold-based, multi-spinneret system. Each spinneret is connected to a manifold, which is fluidly connected to a supply reservoir. The solution feed rate can be controlled by the use of a pressurized fluid that is applied to the reservoir to control the rate of distribution.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally 12.00 inches). The DC power supply is also energized to a predetermined value (optimally 19 kV for this application).

  The pump is energized and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump mechanically moves the barrel through the syringe and moves it at a predetermined rate to control the flow rate. If a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret.

  The desired computer program is now run to obtain the appropriate fabric properties (eg, thickness, area density, dimensions). This computer program is means for storing parameters for a predetermined desired fabric output. This computer program instructs the motion controller to create the appropriate number of paths until the desired material thickness or area density is obtained.

  After the program is run and stopped, the power source and pump are turned off and the substrate is removed from the spinning cavity with the newly electrospun material remaining on the substrate. This material is cured prior to removal from the substrate. Preferably, for this application, the material is cured for at least 3 hours. The material is then removed from the substrate by gradually pulling the corners of the screen until the material separates from the screen. This process can be accelerated using radiant heat or convective heat, preferably below the glass transition temperature of the spun polymer.

Then, the material, washing solution (preferably, deionized water, CO _2, methanol, alcohols, xylene, sterile water) in, is rinsed for 2 minutes. The purpose of this rinsing step is to remove any surface drug that may be present. It is desirable to remove surface drug. This is because these polymers are designed to deliver therapeutic levels of drugs at a predetermined rate. If not removed, the surface drug is delivered immediately at an uncontrolled rate in addition to the intended dosage. The presence of the surface drug is due to leaching that occurs while the polymer and solvent are cured. This material is then dried.

  The newly formed material is then cut to a predetermined size and shape change. The size and shape of this material is determined by customer requirements or by the intended use when packaged based on the application specific application. The amount of drug per unit of area present in the material is considered. Notably, since the drug is delivered directly to the tissue in contact with the material, the amount of drug required for a given application is to achieve a similar effect of giving the drug orally or by injection Extremely less than needed.

Here, the material is ready for inspection and packaging. The inspection is at least one “execution” to determine the properties of this material (eg, thickness, porosity, and area density, tensile strength, suture retention and dosage removed using chemical extraction). One or more samples are tested. The optimum values for these characteristics will vary widely with the intended application. Some orthopedic applications require thicker (0.01 inches), more porous membranes (pores larger than 100 microns) (eg, small scar repair). For most vascular applications, thinner (on the order of 0.002 inches) and lower porosity (less than 30 cc / cm ² / min with 50 micron pores) are appropriate. One or more assays are also performed to determine the actual drug content. If acceptable, the other pieces are individually packaged in separate containers. A pouch made from a lint-free material (eg, Tyvek® from DuPont®) provides sufficient protection for these pieces. Finally, the material and pouch are sterilized using ETO, gamma rays, electron beams, and the like.

(Process for making radiation delivery material)
Electrospinning can be used to create materials that can deliver radioisotopes to target sites in vivo. β-ray emitting isotopes are preferred. This is because beta radiation has a low penetration depth and is ideal for applications where the source material is in regulatory contact with the target tissue. There are two preferred methods of making materials that can deliver radioisotopes. The first method spins “non-radioactive” isotopes into the electrospun material. This material can be made "radioactive" by subjecting the isotope-containing material to radiation. This method reveals the need for increased radiation protection during manufacturing. The second method spins “radioactive” isotopes into the material being electrospun. Each method has other advantages.

  Non-radioactive spinning processes increase the shelf life of the material. This is because radioactive decay does not begin until the material is charged before use or after the material is inserted into the body. However, the selection of isotopes for this application is limited to some extent. Not all isotopes absorb radiation at the same time. If the absorption time is too long, the polymer will degrade before the membrane is sufficiently radioactive. Thus, radioactive spinning provides a way to utilize more isotopes. Both manufacturing processes are relatively easy to implement using the advantages of the present invention.

The first process, where non-radioactive isotopes are spun into the material, begins with the creation of a polymer solution (solvent and precursor isotopes). This polymer is preferably 17.90% by weight PLA. The solvent is preferably 82.10% by weight HFIP and the precursor isotope is preferably ¹⁶⁹ thulium oxide, 1% of the polymer weight. Thulium compounds have an affinity to accept neutrons from bombardments in nuclear reactors. The polymer and solvent are mixed together, then the isotope is added and completely dissolved. A substrate (eg, a coarse mesh screen) is used as the target plate so that the material can be removed from the plate without damage. However, to become a target plate, the substrate must conduct electricity so that it can be grounded. Grounding the substrate, such as by connecting to a ground cable, is essential to establish a potential between the spinneret and the substrate. An extensible material (eg, a screen) is preferred as the substrate so that the material is easily removed from the substrate when the substrate is stretched.

  The electrospinning device motion controller and computer are energized. The MD2 computer program for the motion controller is started. Prior to running this program, a predetermined amount of solution (preferably 3.2 mL) is transferred to the spinneret. If a barrel system is used, the piston is inserted into the bore of the spinneret barrel, the barrel assembly is turned over, and the piston is pushed until all air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The barrelless system is a manifold based, multiple spinneret system. Each spinneret is connected to a manifold, which is fluidly connected to a supply reservoir. The flow rate of the solution can be controlled by the use of pressurized fluid, which is applied to the reservoir to control the rate of dispensing.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally 12.00 inches). The DC power supply is also energized to a predetermined value (optimally 23 kV for this application).

  The pump is energized and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump is mechanically moved at a predetermined rate through the barrel through the syringe to control the flow rate. If a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret. The desired computer program is now executed to obtain the appropriate fabric properties (eg, thickness, area density, dimensions). This computer program is means for storing parameters for a predetermined desired fabric output. The computer program supports the motion controller and creates the appropriate number of passages until the desired material thickness or area density is obtained.

  After this program is run and shut down, the power supply and pump are turned off and the substrate is removed from the spinning cavity with the newly electrospun material remaining on the substrate. This material is cured prior to removal from the substrate. Preferably, for this application, the material is cured for at least 3 hours. The material is then removed from the substrate by gradually pulling the corners of the screen until the material leaves the screen.

Then, the material, washing solution (preferably, deionized water, CO _2, methanol, alcohols, xylene, sterile water) in, is rinsed for 2 minutes. The purpose of this rinsing step is to remove any surface isotopes that may be present. It is desirable to remove surface isotopes. This is because the polymer is designed to deliver therapeutic levels of isotopes at a predetermined rate. If surface isotopes are not removed, they deliver radiation at an uncontrolled rate in addition to the intended extent. The presence of surface isotopes is due to leaching that occurs while the polymer and solvent are cured. Once this material is rinsed, it is dried.

  The newly formed material is then cut into pieces of a predetermined size and shape (preferably determined by customer requirements). The desired dose and dosage time per unit area is taken into account, which is determined by the isotope half-life. This material is now easily investigated and packaged. The survey, at a minimum, tests multiple samples per “run” to determine material properties such as thickness, porosity and area density. The optimum value for each depends on customer requirements. One or more assays are also performed to determine the actual drug content. If acceptable, the other pieces are individually packaged in separate containers. A pouch made from a lint-free material (eg, Tyvec® from DuPont) protects the piece well.

  The material and pouch are placed in a nuclear reactor and ready to receive neutrons. The amount of radioactivity received is directly proportional to the amount of time spent in the reactor and the energy level in the reactor. The reactor used was a MITR-II, a tank-type reactor owned by Massachusetts Institute of Technology (MIT). Preferably, the material is placed in the container for between 30 and 60 minutes, more preferably for 40 and 50 minutes, and the power of the container is preferably between 1 and 10 megawatts And more preferably between 3 and 7 megawatts. Positive results were obtained by placing thallium doped polyurethane for 42 minutes at 5 megawatts. After an appropriate time, a pouch containing new radioactive material is subjected to the assay, the actual energy level is determined, and then sterilized.

The second method of producing radioactive material is virtually the same as the first method described above with some exceptions. A preferred isotope is ⁴⁵ calcium chloride, which has an appropriate beta energy level, half-life, and is relatively harmless. This isotope is mixed with the solution as described above using suitable handling means deemed to work to obtain the radioactive material. The only other exception is that no material can enter the reactor after it has been produced. This is because it is already radioactive.

(Process for making membranes from high melting thermoplastics)
A preferred method of using electrospinning techniques is described herein for making materials that usually require large amounts of heat (above 600 F) to be melted and extruded or spun into fibers. The However, when the material is mixed with a solvent, the material is sufficiently soluble even below the melting point.

  Thus, initially a polymer-based solution is preferably developed from a solution of polymer and solvent. A preferred polymer solution for this application is a low crystalline polyetherimide (eg, Ultem® from General Electric Plastic®) (18.00 wt%) in a solvent (preferably chloroform). ) (82.00% by weight). This mixture is completely dissolved. Other acceptable polymers for this application include PEEK, PTFE, PEK, PTFE, and pitch carbon graphite. If it is desirable to use a less crystalline polymer (eg, PU or Ultem) or a highly volatile solvent (eg, chloroform, xylene, HFIP, or acetone), additional steps are performed to target the fiber Ensure that these fibers are moist when hitting. These steps include exchanging the atmosphere in the spinning chamber by increasing the pressure in the spinning chamber or decreasing the temperature of the chamber. Alternatively, the solvents can be mixed so that they are less volatile.

  A coarse mesh screen (preferably aluminum) is placed at the bottom of the spinning cavity for use as a substrate. This substrate is finally connected to a positively charged cable.

  Energy is applied to the motion controller and computer of the electronic spinning device. The MD2 computer program for the motion controller is started. Prior to running the program, a predetermined amount of solution (depending on the amount of material made) is transferred to the spinneret. If a barrel system is used, the piston is inserted into the bore of the spinneret barrel, the barrel assembly is inverted, and the piston is pushed until all air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The barrelless system is a manifold-based multi spinneret system. Each spinneret is connected to a manifold, which is fluidly connected to a supply reservoir. The solution feed rate can be controlled by the use of a pressurized fluid, which is applied to the reservoir to control the dispensing rate.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally 9.00 inches). When a positively charged wire is clamped to the needle plate and it exits the needle tip, it charges the solution. The ground cable is now connected to the substrate (connection plate).

  A cooling process is used here to ensure that the solvent does not evolve from the polymer until a membrane is formed on the substrate. Failure to perform this cooling step results in clogging of the needle tip. This volatile evolution can also be reduced using polymers with high pressure or a low degree of crystallinity. The cooling process is performed using a compressed gas to reduce the temperature of the polymer solution inside the spinneret to a temperature of -35 ° C. This temperature is maintained during the spinning process.

  The DC power supply is also energized to a predetermined value, which is optimally 23 kV for this application. Energy is applied to the pump and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump mechanically moves the barrel by the syringe at a predetermined speed to control the flow rate. When a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret. The particular pump type is not as important as maintaining a continuous flow rate.

  The desired computer program is now executed to obtain the desired sample size. Computer programs are similar to CNC machining operations. The operator defines the X, Y, and Z coordinates, time and velocity to the next point. The program can be cycled as many times as necessary to produce thin layers in each pass until the desired thickness is achieved, or achieve the desired thickness in a single pass by adjusting the translation speed Can do. The desired computer program is now run to obtain the appropriate fabric properties (eg, thickness, area density, dimensions). The computer program is a means for storing parameters for a predetermined desired fabric output. The desired area density and material thickness are determined by customer requirements. For a given polymer flow rate and polymer to solvent ratio, the membrane can be spun to a given area density based on the time of spinning and the size of the spinning area.

  After the program is run and stopped, the power and pump are turned off, the substrate is removed from the spinning cavity, and new electrospun material remains on the substrate. The material (still bonded to the substrate) is preferably placed in a furnace (already preheated to 450 ° F.) for 15 minutes. It should be noted that fabric properties (eg, stiffness, thickness, strength, and texture) can be altered during the heating procedure, if desired. In addition, the fabric can have the desired reverse surface properties of the fabric. The weight can be applied to the fabric by placing a sample on or between the materials having a weight added to compress the material during this process, providing more surface area for intra-fiber adhesion .

  When the material is calendered, the material is compressed with a roll tube having a pressure of 1500 psi. Doing this improves the strength of the material and increases the thickness uniformity of the material and decreases the porosity and permeability of the material.

  This material is then removed from the substrate by gradually pulling over the corners of the screen until the material is separated from the screen. The edges of the material appear to be thinner than the relatively uniform middle part. These edges are removed and the remainder of the material (with a uniform area density) is cut to dimensions specific to the application desired by the customer. For example, a horseshoe-shaped 5-10 mm thick piece is ideal for a knee meniscus graft.

  This material is now ready for inspection and packaging. The inspection, at a minimum, tests one or more samples per “run” to determine material properties such as thickness, porosity, and area density. Again, these variables are application specific and highly selectable.

(Process for producing reinforced electrospun material using scrim)
Here, a preferred method of using electrospinning techniques is described for making electrospinning to cover the scrim. The scrim is used for applications where additional material strength is required. An example of application is a hernia mesh with anti-adhesion properties. For hernia mesh. PGA, PCL, PDO, HA, polymers such as hydrogels, or mixtures thereof, more standard woven mesh (eg, Prolene ^TM is manufactured by Johnson & Johnson) is spun directly onto. Furthermore, the same technique can be used to spin the polymer directly onto the stent surface. A polymer-based solution was preferably prepared from the polymer and solvent and the solution was spun onto the surface of the fabric scrim or stent. In some cases, a priming step is required as discussed above, while in other cases wet microfibers are sufficient to bond the membrane directly to the scrim.

  A preferred polymer solution for this application is to mix a polymer (preferably 7.5% polydioxanone (PDO) by weight) with a solvent (preferably 92.50% HFIP by weight) and mix the mixture. Furthermore, before spinning, the polypropylene scrim must be clean to receive the electrospun material, preferably a 33% butanol and 67% hexane wash solution. Is achieved by immersing the polypropylene scrim in the cleaning solution for about 30 seconds and drying the scrim.

  In addition to being cleaned, the scrim can also be surface coated or primed. The above polymer spinning solution can be used as a coating solution. The best results are achieved by immersing the scrim in the solution for about 1 minute and removing the scrim therefrom. For optimum adhesion between the scrim and the electrospun cover, it is important that the surface of the scrim is not dried before electrospinning is started. Preferably, the priming coat is less than 10 microns thick.

  The scrim substrate is placed on the ground plate at the bottom of the spinning cavity. The scrim is electrically insulating so that the plate is well grounded. The needle height is then adjusted to 8 inches above the top surface of the scrim.

  Energy is applied to the motion controller and computer of the electrospinning device. The MD2 computer program for the motion controller is started. Prior to running the program, a predetermined amount of solution (preferably 4.0 mL) is transferred to the spinneret. If a barrel system is used, the piston is inserted into the bore of the spinneret barrel, the barrel assembly is inverted, and the piston is pushed until all air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The barrelless system is a manifold-based multi spinneret system. Each spinneret is connected to a manifold, which is fluidly connected to a supply reservoir. The solution feed rate can be controlled by the use of a pressurized fluid, which is applied to the reservoir to control the dispensing rate.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally 8 inches), held there for 1 minute, and 12 inches high for the rest of the process Adjust the height. Start with an 8 inch needle height for 1 minute to provide an initial wet cover that adheres well to the substrate. The remainder of the process is later raised to a 12 inch needle height to produce the appropriate height material with the desired porosity. The DC power supply is also energized to a predetermined value, which is optimally 18 kV for this application. Energy is applied to the pump and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump mechanically moves the barrel by the syringe at a predetermined speed to control the flow rate. When a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret. The particular pumping method used is not critical as long as a continuous steady flow is maintained.

  The desired computer program is now executed to obtain the desired sample size. Computer programs are similar to CNC machining operations. The operator defines the X, Y, and Z coordinates, time and velocity to the next point. The program can be cycled as many times as necessary to produce thin layers in each pass until the desired thickness is achieved, or achieve the desired thickness in a single pass by adjusting the translation speed Can do. The desired computer program is now run to obtain the appropriate fabric properties (eg, thickness, area density, dimensions). The computer program is a means for storing parameters for a predetermined desired fabric output. The desired area density and material thickness are determined by customer requirements. For a given polymer flow rate and polymer to solvent ratio, the membrane can be spun to a given area density based on the time of spinning and the size of the spinning area.

  After the program is run and stopped, the power and pump are turned off, the substrate is removed from the spinning cavity, and new electrospun material and scrim remain on the substrate. This material is cured before being removed from the substrate. Preferably, for this application, the material can be cured for at least 3 hours. This material is then removed from the substrate by gradually pulling over the corners of the screen until the material is separated from the screen.

  The newly formed material is then cut into pieces of a predetermined size and shape. The size and shape of this material is determined by customer requirements or, if packaged based on use, by the specific application and intended use.

  This material is now ready for inspection and packaging. The inspection, at a minimum, tests one or more samples per “run” to determine material properties such as thickness, porosity, area density, suture retention, and ball burst. Each optimal value is determined by customer requirements. If acceptable, the other pieces are individually packaged in separate containers. A pouch made of lint-free material such as Tyvek® made by DuPont® properly protects the piece. Finally, the material and pouch are sterilized.

(Process for making woven electrospun material using scrim)
Here, a preferred method of using electrospinning techniques to make woven electrospinning to cover the scrim is described. This woven surface uses a small tack-down spot (the part of the fabric that is locally bound by the embossing mold) to create a more stable membrane. In addition, this fabric improves the membrane's ability to wick fluid, improves the flexibility of the material, better covers the material, and reduces stiffness. This process is initially identical to the process described above for making an electrospun material using a scrim.

  The weaving aspect of this process begins after the scrim is removed from the spinning cavity. Again, the scrim is not removed from the screen. However, before the scrim is cured for 3 hours, the electrospun membrane is placed on a woven surface mold or rotating mold and a woven surface imprint is applied to the outer surface of the membrane.

  This material can then be cured for 3 hours as described above. The rest of the packaging and sterilization process remains the same.

(Process for making fabrics with controlled drug release rate)
Here, a preferred method of using the electrospinning technique of the present invention to control the drug release rate of a drug eluting object or fabric is described. By covering the object or fabric with an electrospun cover having a very small gap, the drug release kinetics of the object or fabric can be controlled. The manufacturing method is very similar to the process for making reinforced electrospun materials using scrim.

  A polymer-based solution is preferably prepared from a polymer and a solvent, and the solution is spun onto the surface of a drug-containing object (eg, a fabric, preferably an electrospun fabric, or a stent). As discussed above, in some cases a priming step is required, but in other cases wet microfibers are sufficient to bond the membrane directly to the scrim.

  A preferred polymer solution for this application is to mix a polymer (preferably 7.5% polydioxanone (PDO) by weight) with a solvent (preferably 92.50% HFIP by weight) and mix the mixture. Furthermore, before spinning, the drug-containing cloth or object must be clean so as to receive the electrospun material, unless the substrate material itself is electrospun before spinning. A washing solution of% butanol and 67% hexane is preferred, washing is accomplished by immersing the polypropylene scrim in the washing solution for about 30 seconds and allowing the scrim to dry. Containing objects or fabrics can also be surface coated or primed. The best results are achieved by immersing the object or fabric in the solution for about 1 minute for optimal adhesion between the object or fabric and the electrospun cover. It is important that the surface not be dried before electrospinning is started, preferably the priming coat is less than 10 microns thick.

  The drug-containing object or cloth is placed on the bottom of the spinning cavity on the ground plate. If the object is electrically isolated, the plate must be well grounded. The needle height is then adjusted to 8 inches above the top surface of the scrim. If the object is a cloth, the cloth is placed on a grounded substrate.

  Energy is applied to the motion controller and computer of the electrospinning device. The MD2 computer program for the motion controller is started. Prior to running the program, a predetermined amount of solution (preferably 4.0 mL) is transferred to the spinneret. If a barrel system is used, the piston is inserted into the bore of the spinneret barrel, the barrel assembly is inverted, and the piston is pushed until all air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The barrelless system is a manifold type multi spinneret system. Each spinneret is connected to a manifold and fluidly connected to a supply reservoir. The solution feed rate can be controlled through the use of pressurized fluid applied to the reservoir to control the delivery rate.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally starting at 8 inches where it is held for 1 minute and the rest Height adjusted to 12 inches for the process). Starting with a needle height of 8 inches (1 minute) provides an initial wet cover that adheres well to the substrate. By raising the needle height to 12 inches later for the rest of the process, a sufficiently high material layer with the desired porosity is formed. The DC power supply is also started at a predetermined value (for this application, it is optimally 18 kV).

  The pump is started and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump moves the barrel through the syringe at a predetermined rate to control the flow rate. When a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret. The particular pumping method used is not critical as long as a continuous and stable flow rate is maintained.

  Here, a desired computer program is executed to obtain the desired sample dimensions. The computer program is similar to CNC machine operation. The operator defines the X, Y and Z coordinates, time and speed to the next point. This program is repeated as many times as necessary until a thin layer is produced in each passage until the desired thickness is achieved, or the desired thickness in a single passage can be achieved by adjusting the travel speed. It is. Here, a desired computer program is executed in order to obtain suitable fabric properties (eg, thickness, area density, dimensions). The computer program is means for storing parameters for a predetermined desired fabric output. The desired area density and material thickness can be spun for a given polymer flow rate and polymer to solvent ratio determined by the user's requirements until a given area density is achieved based on the spinning time and size of the spinning region.

  After the program is run and stopped, the power supply and pump are switched off and the substrate is removed from the spinning cavity, leaving the newly electrospun material and scrim on the substrate. This material is cured before being removed from the substrate. Preferably, for this application, the material is cured for at least 3 hours. This material is then removed from the substrate by gradually pulling at the corners of the screen until the material is separated from the screen.

  If the object is a fabric, the fabric is spun, placed on the substrate, and the process is repeated so that both sides of the fabric are covered. If the object is three-dimensional, the object is properly manipulated and the process is repeated until the desired amount of object is covered. Preferably, this object is spun during the initial cover process.

  If the object is a fabric used as a drug eluting dressing, the newly formed material is cut into sections of a predetermined size and shape. The size and shape of this material is determined by the user's requirements or by the intended use when packaged based on use specific application.

  Here, the material is ready for inspection and packaging. With minimal inspection, one or more samples per “run” are tested to determine material properties (eg, thickness, porosity, area density, suture retention, and ball burst). The optimum value for each is determined by the user's request. If acceptable, the other sections are individually packaged in separate containers. A pouch made of a lint-free material (eg, Tyvek® manufactured by DuPont®) provides sufficient protection for this section. Finally, the material and pouch are sterilized.

(Process for bonding pre-spun material to object)
Preferred methods are described herein using electrospinning techniques to bond a pre-spun polymer to a substrate (eg, a stent, scrim, or other object). As described above, the polymer solution adheres to the substrate when electrospun in a manner that produces wet microfibers in contact with the substrate object. It has also been demonstrated that wet spun polymers are particularly adhesive to other spun polymers of the same material. Accordingly, the electrospinning technique of the present invention is well-suited for producing an adhesive layer that can be used to bond pre-spun polymer fibers to an object (particularly a polymer fabric pre-spun with an adhesive polymer). If it is the same as that).

  A preferred polymer solution for this application is produced by mixing the polymer (preferably the same polymer used to produce the material to be bonded to the object) and the solvent. Good results are obtained by bonding PET to stainless steel using 12% by volume PET and 88% by volume HFIP and fully dissolving the mixture. Good results are also obtained by bonding spun PGA films to knitted PET and polypropylene webs using 14 wt% PGA and 86 wt% HFIP.

  Prior to spinning, if the substrate is a propylene scrim, the scrim must be washable to receive the electrospun material. A wash solution of 33% butanol and 67% hexane is preferred. Cleaning is accomplished by immersing the polypropylene scrim in this cleaning solution for about 30 seconds and allowing the scrim to dry. In addition to cleaning, the scrim must also be surface coated or primed. The above polymer spinning solution can be used as a coating solution. The best results are achieved by immersing the scrim in this solution for about 1 minute and removing the scrim from it. For optimal adhesion between the scrim and the electrospinning cover, it is important that the surface of the scrim is not dried before electrospinning begins. Preferably, the priming coat is less than 10 microns thick.

  The substrate is disposed on the ground plate at the bottom of the spinning cavity. If the substrate is an electrical insulator, the plate must be well grounded. The needle height is then adjusted to 8 inches on the top surface of the substrate.

  The motion controller and computer of the electrospinning device are activated. The MD2 computer program for the motion controller is initialized. Prior to program execution, a predetermined amount of solution (preferably 4.0 mL) is transferred to the spinneret. If a barrel system is used, the piston is inserted into the bore of the spinneret barrel, the barrel assembly is inverted, and the piston is pushed down until all the air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. This barrelless system is a manifold type multi spinneret system. Each spinneret is connected to a manifold and fluidly connected to a supply reservoir. The solution feed rate can be controlled through the use of pressurized fluid applied to the reservoir to control the delivery rate.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally starting from 8 inches, the substrate covers the wet polymer cover Is guaranteed). The DC power supply is also started at a predetermined value (for this application, it is optimally 18 kV).

  The pump is started and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump moves the barrel through the syringe at a predetermined rate to control the flow rate. When a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret. The particular pumping method used is not critical as long as a continuous and stable flow rate is maintained.

  Here, a desired computer program is executed to obtain the desired sample dimensions. The computer program is similar to CNC machine operation. The operator defines the X, Y and Z coordinates, time and speed to the next point. This program is designed to provide a single wet cover for the entire substrate.

  After the program is run and stopped, the power supply and pump are switched off and the substrate is removed from the spinning cavity, leaving a newly electrospun cover on the substrate. The pre-spun material is then wrapped around the substrate before the newly spun cover is cured.

(Process for covering an object with a polymer layer)
A preferred method of using electrospinning techniques to create an electrospun cover for an object (eg, a stent) is described herein. A polymer-based solution (preferably a polymer and solvent solution) is prepared and spun on the surface of the fabric scrim or stent. In some cases, a priming step as described above is required, and in other cases, wet microfibers are sufficient to bond the stent directly to the membrane.

  A preferred polymer solution for this application is mixing the polymer (preferably 7.5% by weight polydioxanone (PDO)) and solvent (preferably 92.50% by weight HFIP) to completely dissolve this mixture. Is generated. In addition, prior to spinning, the stent must be able to be cleaned to receive the electrospun material. A wash solution of 33% butanol and 67% hexane is preferred. Cleaning is accomplished by immersing the stent in this cleaning solution for about 30 seconds and allowing the stent to dry.

  In addition to cleaning, the stent can also be surface coated or primed. The above polymer spinning solution can be used as a coating solution. The best results are achieved by immersing the stent in this solution and removing the stent from it. For optimal adhesion between the stent and the electrospinning cover, it is important that the surface of the stent is not dried before electrospinning begins. Preferably, the priming coat is less than 10 microns thick.

  The stent substrate is disposed on the ground plate at the bottom of the spinning cavity. The needle height is adjusted to 8 inches on the top surface of the scrim. The motion controller and computer of the electrospinning device are activated. The MD2 computer program for the motion controller is initialized. Prior to program execution, a predetermined amount of solution (preferably 4.0 mL) is transferred to the spinneret. If a barrel system is used, the piston is inserted into the bore of the spinneret barrel, the barrel assembly is inverted, and the piston is pushed down until all the air is exhausted from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. This barrelless system is a manifold type multi spinneret system. Each spinneret is connected to a manifold and fluidly connected to a supply reservoir. The solution feed rate can be controlled through the use of pressurized fluid applied to the reservoir to control the delivery rate.

  The pump is then connected to the spinneret assembly and the needle height is adjusted to a predetermined height (optimally starting at 8 inches and held for 1 minute and the rest of the process Adjusted to a height of 12 inches). Starting with a needle height of 8 inches (1 minute) provides an initial wet cover that adheres well to the substrate. By raising the needle height to 12 inches later for the rest of the process, a sufficiently high material layer with the desired porosity is formed. The DC power supply is also started at a predetermined value (for this application, it is optimally 18 kV).

  The pump is started and adjusted to a predetermined flow rate (preferably 0.60 mL / min). If a syringe barrel system is used, the pump moves the barrel through the syringe at a predetermined rate to control the flow rate. When a barrelless system is used, the pressure is manipulated to control the flow rate through the spinneret. The particular pumping method used is not critical as long as a continuous and stable flow rate is maintained.

  Here, a desired computer program is executed to obtain the desired sample dimensions. The computer program is similar to CNC machine operation. The operator defines the X, Y and Z coordinates, time and speed to the next point. This program is repeated as many times as necessary until a thin layer is produced in each passage until the desired thickness is achieved, or the desired thickness in a single passage can be achieved by adjusting the travel speed. It is. Here, a desired computer program is executed in order to obtain suitable fabric properties (eg, thickness, area density, dimensions). The computer program is means for storing parameters for a predetermined desired fabric output. The desired area density and material thickness are determined by user requirements. For a given polymer flow rate and polymer to solvent ratio, the membrane can be spun until a given area density is achieved based on the spinning time and size of the spinning region.

  After the program is run and stopped, the power supply and pump are switched off and the stent is removed from the spinning cavity, leaving a newly electrospun cover on the stent.

(Process for coating objects with polymers)
The above covered stent is optimally adapted to form a coated stent that avoids many if not all of the problems that prior art coated stents could not overcome. . This coating method comprises heating the cover stent or other object covered with a fibrous polymer layer to a temperature at which the electrospun microfibers spreading in the gap formed by the braid of the stent are separated. Is included. When these braided fibers separate, they tend to shrink and collect on the nearest wire. This temperature is maintained until all of the braided microfibers are separated and collected on the individual wires. The stent is coated here, as opposed to being covered.

  Notably, the coat retains some of the fiber quality. It has been found that increasing the temperature, or increasing the heating time, or both, effectively reduces the fibrity of the coat. The decrease in the fiber of the coat also reduces the porosity of the coat and the size of the gap between the fibers. If the covered stent is heated long enough or hot enough, the polymer melts and forms a non-fibrous coat on the wire of the stent.

  If the object to be coated is temperature sensitive, the same result can be obtained without heating. Instead of heating the covered object, the object is placed in an atmosphere filled with gas from a solvent. By placing an object in the solvent gas chamber, the cover softens and behaves as if heated. Similarly, the fibrous properties of the resulting coat can be affected by the time elapsed in the chamber and / or the concentration of solvent gas. The solvent used to form the gas can be the same solvent that is mixed with the polymer to produce the polymer solution for electrospinning.

(Process for electrospinning composite materials)
Preferred methods of using electrospinning techniques for electrospinning composite materials that combine the advantages of two or more polymers into one material are now described. The preferred composite materials described herein combine the strength of PET with the elasticity of PU. Two polymer-based solutions (preferably each of the polymer and solvent) are developed and the solutions are spun together onto the substrate surface.

  The first polymer solution for this application is to mix the polymer (preferably 7.50 wt% PET) with the solvent (preferably 92.50% HFIP) and dissolve the mixture completely. Developed by The second polymer solution for this application consists of mixing the polymer (preferably 7.50% by weight PU) with a solvent (preferably 92.50% DMAC), and thoroughly mixing the second mixture. Developed by dissolving in

  Thereafter, both polymer solutions are placed in separate spinnerets. However, when these polymers and solvents are mixed, they can be placed in a single spinneret. These spinneret needles are then adjusted to a height of 8 inches above the substrate. If the composite material is to be spun onto the scrim surface, the scrim is cleaned and primed as described above, and the spinnerets are 8 inches above the scrim surface. Adjusted.

  Energy is applied to the operation control apparatus and the electrospinning device computer. The MD2 computer program for this motion control device is initialized. A predetermined amount of the above solution (preferably 4.0 mL) is transferred into the spinneret before running the program. If a barrel system is used, the piston is inserted into the spinneret barrel hole, the barrel assembly is inverted, and the piston is pushed until air is expelled from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The barrelless system is a manifold based multi spinneret system. Each spinneret is coupled to a manifold, which is in fluid communication with a supply reservoir. The solution feed rate can be controlled through the use of pressurized fluid, which is applied to the reservoir to control the dispensing rate.

  The pump is then connected to the spinneret assembly and the DC power supply is also energized to a predetermined value. This value is optimally 18 kV for this application. The pump is energized and adjusted to a predetermined flow rate (preferably 0.60 mL / min). When a syringe barrel system is used, the pump mechanically moves the barrel through the syringe at a predetermined speed to control the flow rate. If a barrelless system is used, the pressure can be manipulated to control the flow rate through the spinneret. The particular pumping method used is not critical as long as a continuous steady flow is maintained.

  The desired computer program is now run to obtain the desired sample dimensions. This computer program is similar to CNC machining operations. The operator defines the X, Y, and Z coordinates, time, and speed to the next point. This program can produce a thin layer on each path by cycling as many times as necessary until the desired thickness is achieved, or by adjusting the moving speed accordingly, a single The desired thickness can be achieved in the path. The desired computer program is now run to obtain the appropriate fabric characteristics (eg, thickness, area density, dimensions). This computer program is a means of storing parameters for a predetermined desired fabric output. The desired area density and material thickness are determined by consumer demand. For a given polymer flow rate and polymer to solvent ratio, the membrane can be spun to a given area density based on the spinning time and the size of the spinning area.

  After the program is run and stopped, the power supply and pump are turned off, the substrate is removed from the spinning cavity, and the newly electrospun material and scrim remain on the substrate. This material is made severable before being removed from the substrate. Preferably, for this application, the material is cured for at least 3 hours. This material is then removed from the substrate by slowly pulling the corners of the screen before separating from the screen.

  The newly formed material is then cut into pieces of a predetermined size and shape. The size and shape of this material is determined by consumer demands or by the intended use when packaged based on application specific applications.

  This material is now ready for inspection and packaging. Inspection, at a minimum, tests one or more samples at a “run” time to determine the properties of the material (eg, thickness, porosity, area density, suture retention, and ball burst). burst)). The optimal value for each is determined by its application and / or consumer demand. If allowed, the other pieces are individually packaged in separate containers. A pouch made from a lint-free material (eg, Tyvek® manufactured by DuPont®) fully protects these pieces. Finally, the material and pouch are sterilized.

(Process for electrospinning composite materials for fuel cells)
Here, a preferred method of using electrospinning techniques for electrospinning composite materials optimally adapted for use in fuel cells is described. The preferred composite materials described herein combine the strength of PET with the elasticity of Nafion® manufactured by DuPont®. Two polymer-based solutions (preferably each of the polymer and solvent) are developed and the solutions are spun together onto the substrate surface.

  The first polymer solution for this application is to mix the polymer (preferably 7.50 wt% PET) with the solvent (preferably 92.50% HFIP) and dissolve the mixture completely. Developed by The second polymer solution for this application is 7.50 wt% Nafion® (a barrier polymer designed to filter ions) with solvent (preferably 92.50% HFIP). Developed by mixing and completely dissolving the second mixture. Nafion® is also available in solution form and can be used in this form to achieve acceptable results. Thereafter, both polymer solutions are placed in separate spinnerets. However, when these polymers and solvents are mixed, they can be placed in a single spinneret. These spinneret needles are then adjusted to a height of 8 inches above the substrate.

  Energy is applied to the operation control apparatus and the electrospinning device computer. The MD2 computer program for this motion control device is initialized. A predetermined amount of the above solution (preferably 4.0 mL) is transferred into the spinneret before running the program. If a barrel system is used, the piston is inserted into the spinneret barrel hole, the barrel assembly is inverted, and the piston is pushed until air is expelled from the barrel. A needle (preferably a 20 gauge needle) is then secured to the end of the barrel.

  Alternatively, if a barrelless system is used, the desired amount of solution is programmed into the computer. The barrelless system is a manifold based multi spinneret system. Each spinneret is coupled to a manifold, which is in fluid communication with a supply reservoir. The solution feed rate can be controlled through the use of pressurized fluid, which is applied to the reservoir to control the dispensing rate.

  The pump is then connected to the spinneret assembly and the DC power supply is also energized to a predetermined value. This value is optimally 18 kV for this application. The pump is energized and adjusted to a predetermined flow rate (preferably 0.60 mL / min). When a syringe barrel system is used, the pump mechanically moves the barrel through the syringe at a predetermined speed to control the flow rate. If a barrelless system is used, the pressure can be manipulated to control the flow rate through the spinneret. The particular pumping method used is not critical as long as a continuous steady flow is maintained.

  The desired computer program is now run to obtain the desired sample dimensions. This computer program is similar to CNC machining operations. The operator defines the X, Y, and Z coordinates, time, and speed to the next point. This program can produce a thin layer on each path by cycling as many times as necessary until the desired thickness is achieved, or by adjusting the moving speed accordingly, a single The desired thickness can be achieved in the path. The desired computer program is now run to obtain the appropriate fabric characteristics (eg, thickness, area density, dimensions). This computer program is a means of storing parameters for a predetermined desired fabric output. The desired immune density and material thickness are determined by consumer demand. For a given polymer flow rate and polymer to solvent ratio, the membrane can be spun to a given area density based on the spinning time and the size of the spinning area.

  After the program is run and stopped, the power supply and pump are turned off, the substrate is removed from the spinning cavity, and the newly electrospun material and scrim remain on the substrate. This material is made severable before being removed from the substrate. Preferably, for this application, the material is cured for at least 3 hours. This material is then removed from the substrate by slowly pulling the corners of the screen before separating from the screen.

  The newly formed material is then cut into pieces of a predetermined size and shape. The size and shape of this material is determined by consumer demands or by the intended use when packaged based on application specific applications.

  This material is now ready for inspection and packaging. Inspection, at a minimum, tests one or more samples at a “run” time to determine the properties of the material (eg, thickness, porosity, area density, suture retention, and ball burst). burst)). The optimal value for each is determined by its application and / or consumer demand. If allowed, the other pieces are individually packaged in separate containers. A pouch made from a lint-free material (eg, Tyvek® manufactured by DuPont®) fully protects these pieces. Finally, the material and pouch are sterilized.

  Those skilled in the art will further appreciate that the present invention may be implemented in other specific forms without departing from its spirit or core characteristics. It is to be understood that other variations within the scope of the present invention are contemplated in that the above description of the invention discloses only exemplary embodiments thereof. Accordingly, the present invention is not limited to the specific embodiments described in detail herein. Rather, reference should be made to the appended claims as indicating the scope and content of the invention.

FIG. 1 is a schematic description of the basic components of a known electrospinning apparatus. FIG. 2 is a perspective view of a preferred electrospinning apparatus of the present invention. FIG. 3 is a perspective view of a power supply according to a preferred embodiment of the present invention. FIG. 4a is a perspective view of a preferred embodiment pump of the present invention. FIG. 4b is a perspective view of an alternative embodiment pump of the present invention. FIG. 5 is a photograph of the covered stent of the present invention. FIG. 6 is a photograph of the elastic electrospun fabric of the present invention. FIG. 7 is a photograph of the electrospun fabric of the present invention having relatively large microfibers. FIG. 8 is a photograph of the electrospun fabric of FIG. 7 showing the edges of the fabric. FIG. 9 is a photograph of the electrospun fabric of the present invention having relatively small microfibers when compared to the electrospun fabric of FIG. FIG. 10 is a photograph of the electrospun fabric of FIG. 9 showing the edges of the fabric.

Claims (116)

A method of making a fiber cover comprising:
Charging the spinneret to a potential for a predetermined location on the target plate;
Placing an object between the spinneret and the predetermined position on the target plate;
Pushing a liquid through the spinneret, thereby transferring at least some of the potential to the liquid, so that the liquid is due to the potential between the liquid and the predetermined position due to the target Forming a flow toward the predetermined position on the plate, whereby the flow spreads into the plurality of nanofibers due to the potential between the liquid and the predetermined position, thereby at least The nanofibers collide with the object instead of reaching the target plate;
Moving the predetermined position on the target plate relative to the object, thereby causing the nanofibers to cover the object. The method of claim 1, further comprising ensuring that the nanofibers are wet when the nanofibers collide with the object. 3. The method of claim 2, wherein when the nanofibers collide with the object, ensuring that the nanofibers are wet is placing the spinneret at a predetermined distance from the object. Including the method. 3. The method of claim 2, wherein, when the nanofibers collide with the object, ensuring that the nanofiber is wet comprises setting the air pressure between the spinneret and the object to a predetermined value. Adjusting the pressure. 3. The method of claim 2, wherein when the nanofibers collide with the object, ensuring that the nanofiber is wet is the temperature between the spinneret and the object is a predetermined value. Adjusting the temperature. The method of claim 1, further comprising rotating the object relative to the flow. 2. The method of claim 1, wherein moving the predetermined position on the target plate relative to the object comprises moving the object onto the predetermined position on the target plate. how to. 2. The method of claim 1, wherein moving the predetermined position on the target plate relative to the object includes moving the predetermined position on the target plate below the object. ,Method. 9. The method of claim 8, wherein the method moves the spinneret with the relative movement of the predetermined position on the target plate so that the spinneret is substantially at the predetermined position. The method further comprising a step remaining directly above. 2. The method of claim 1, wherein placing an object between the spinneret and the predetermined position on the target plate includes between the spinneret and the predetermined position on the target plate. A method of placing a stent. 11. The method of claim 10, wherein the step of moving the predetermined position on the target plate relative to the object rotates the stent over the predetermined position on the target plate, Covering the entire stent with nanofibers. The method of claim 1, wherein pushing the liquid through the spinneret comprises pushing a mixture of polymer and solvent through the spinneret. The method of claim 1, wherein placing an object between the spinneret and the predetermined position on the target plate comprises placing a substrate on the target plate. . 14. The method of claim 13, further comprising removing the cover from the substrate, thereby forming a self-supporting material of nanofibers. 2. The method of claim 1, wherein placing an object between the spinneret and the predetermined position on the target plate includes between the spinneret and the predetermined position on the target plate. Placing the scrim. The method of claim 1, wherein the method comprises:
Charging a second spinneret at a potential relative to the predetermined location on the target plate;
Pushing the second liquid through the second spinneret, thereby transferring at least some of the potential to the liquid so that the liquid is due to the potential between the liquid and the predetermined position Forming a flow towards the predetermined location on the target plate, whereby the flow spreads into the plurality of nanofibers due to the potential between the liquid and the predetermined location Further comprising the step of causing at least some of the nanofibers to collide with the object instead of reaching the target plate. The method of claim 1, further comprising stretching the material, thereby aligning the nanofibers with each other. 13. The method according to claim 12, wherein the step of pushing the mixture of the polymer and the solvent through the spinneret is PLA, PET, PGA, PCL, PDO, collagen, polytetrafluoroethylene, polyactive, polyurethane, polyester. Pushing a mixture of a polymer belonging to the group of polypropylene, polyethylene, silicone and PU with a solvent belonging to the group of HFIP, dichloromethane, dimethylacetamide, chloroform, dimethylformamide, methylene chloride and xylene. The method of claim 1, further comprising the step of weaving the nanofibers. 20. The method of claim 19, wherein the step of weaving the nanofibers heats the nanofibers and applies pressure to the nanofibers on a woven surface, thereby causing the surface fabric to become nanofibers. The way to go. 21. The method of claim 19, wherein the step of weaving the nanofibers uses a woven substrate as an object placed between the spinneret and the predetermined location on the target plate. Moving the substrate fabric to the nanofibers such that the nanofibers dry on the woven substrate. A method of covering an object with a material, the method comprising:
Charging the spinneret with a potential relative to a predetermined location on the target plate;
Placing an object to be covered between the spinneret and the target plate;
Pushing the liquid through the spinneret, thereby transferring at least some of the potential to the liquid so that the liquid is due to the potential between the liquid and the predetermined position Forming a flow toward the predetermined location above, whereby the flow spreads into the plurality of nanofibers due to the potential between the liquid and the predetermined location; The fiber colliding with the object;
Ensuring that when the nanofibers collide with the object, the nanofibers are sufficiently wet to adhere to the object;
Placing the material on the object while the nanofibers are still wet, so that the nanofibers bind the material to the spinneret. 23. The method of claim 22, wherein pushing the liquid through the spinneret comprises pushing a first polymer dissolved in a solvent through the spinneret. 24. The method of claim 23, wherein the step of placing material on the object while the nanofibers are still wet comprises the steps of placing the material on the object while the nanofibers are still wet. Disposing a material of the first polymer. A method of bonding a substrate to a structure, the method comprising:
Providing an electrospinning apparatus;
Providing a binding substance in liquid form;
Introducing the binding substance into the electrospinning device in liquid form;
Operating the electrospinning device so that the binding material extends into nanofibers having an average diameter of less than 100 micrometers;
Directing the nanofibers to a target structure;
Ensuring that the nanofibers remain sufficiently wet when the nanofibers are in contact with the target structure, so that the nanofibers form a thin cover on the target structure, Comprising a plurality of randomly arranged interior spaces. 26. The method of claim 25, wherein the step of providing an electrospinning device includes the following:
Providing a needle operably connected to the fluid conduit;
Providing a pump constructed and arranged to push fluid through the fluid conduit;
Providing a target plate operatively replaced from the needle; and providing a power source constructed and arranged to establish a variable controllable potential between the target plate and the needle. how to. 26. The method of claim 25, wherein the step of providing the binding material in liquid form comprises PLA, PET, PGA, PCL, PDO, collagen, polyactive, polytetrafluoroethylene, polyurethane, polyester, polypropylene, polyethylene, Providing a mixture of silicone and a polymer belonging to the PU group with a solvent belonging to the group of HFIP, dichloromethane, dimethylacetamide, chloroform, dimethylformamide, methylene chloride and xylene. 27. The method of claim 26, wherein introducing the binding material into the electrospinning device in liquid form includes pushing the binding material in liquid form through the fluid conduit. 29. The method of claim 28, wherein pushing the binding material in liquid form through the fluid conduit is accomplished using the pump pushing the binding material in liquid form through the fluid conduit. The way. 27. The method of claim 26, wherein the step of operating the electrospinning device so that the binding material extends into nanofibers having an average diameter of less than 100 micrometers is as follows:
Positioning a needle 12 inches above the target plate;
Controlling the power supply to establish a 19 kV potential between the needle and the plate; and applying a voltage to the pump to push the binder through the fluid line at 0.60 mL / min. A method comprising the steps of actuating and setting. A method of delivering a drug to a target site, the method comprising:
Charging the spinneret with a potential for a predetermined position on the target plate;
Pushing the liquid containing the drug through the spinneret, thereby transferring at least some of the potential to the liquid, so that the liquid is due to the potential between the liquid and the predetermined position, Forming a flow directed to the predetermined location on the target plate, whereby the flow spreads into a plurality of nanofibers due to an electrical potential between the liquid and the predetermined location;
Ensuring that when the nanofibers collide with the target plate, the nanofibers adhere together and are sufficiently wet to form a cloth-like material;
Placing the cloth-like material at a target site in vivo, whereby tissue drains the drug from the cloth-like material at the target site. 32. The method of claim 31, wherein, when the nanofibers collide with the target plate, ensuring that the nanofibers adhere together and are sufficiently wet to form a cloth-like material. Placing the spinneret at a predetermined distance from the target plate. 32. The method of claim 31, wherein, when the nanofibers collide with the target plate, ensuring that the nanofibers adhere together and are sufficiently wet to form a cloth-like material. Adjusting the air pressure between the spinneret and the target plate to a predetermined pressure. 32. The method of claim 31, wherein, when the nanofibers collide with the target plate, ensuring that the nanofibers adhere together and are sufficiently wet to form a cloth-like material. Adjusting the air temperature between the spinneret and the target plate to a predetermined temperature. 32. The method of claim 31, wherein the method comprises:
Placing an object between the spinneret and the predetermined position on the target plate so that at least some of the nanofibers collide with the object instead of reaching the target plate;
Moving the predetermined position on the target plate relative to the object, thereby causing the nanofibers to cover the object with the cloth-like material. 36. The method of claim 35, wherein placing an object between the spinneret and the predetermined position on the target plate includes between the spinneret and the predetermined position on the target plate. Placing the stent. 36. The method of claim 35, wherein placing an object between the spinneret and the predetermined position on the target plate includes between the spinneret and the predetermined position on the target plate. Placing the scrim. 36. The method of claim 35, further comprising priming the object with a prime solution and then placing the object between the spinneret and the predetermined location on the target plate. how to. 39. The method of claim 38, wherein priming the object comprises dip coating the object in the liquid. 32. The method of claim 31, wherein pushing the liquid containing the drug through the spinneret comprises pushing the liquid containing the polymer, drug and solvent through the spinneret. 41. The method of claim 40, wherein the step of pushing a liquid comprising a polymer, a drug and a solvent through the spinneret comprises PLA, PET, PGA, PCL, PDO, collagen, multi-activity, polytetrafluoroethylene, polyurethane A polymer selected from the group of polyester, polypropylene, polyethylene, silicone, and PU and a drug selected from rapamycin, taxol and warfarin and belongs to the group of HFIP, dichloromethane, dimethylacetamide, chloroform, dimethylformamide, methylene chloride and xylene Pushing the liquid containing the solvent. 42. The method of claim 41, wherein pushing the liquid comprising the polymer, drug and solvent through the spinneret comprises 15-20% PLA by mass, 80-85% HFIP by mass, and polymer mass. Pushing a liquid comprising a drug selected from the group of 0.05 to 1% rapamycin, taxol and warfarin. 43. The method of claim 42, wherein forcing the liquid comprising polymer, drug and solvent through the spinneret comprises 17.9% PLA by mass, 82.1% HFIP by mass, and polymer mass. Pushing the liquid comprising a drug selected from the group of 0.05% rapamycin, taxol and warfarin. 42. The method of claim 41, wherein the step of pushing a liquid comprising a polymer, a drug and a solvent through the spinneret comprises PET, PGA, PCL, PDO, collagen, multi-activity, polytetrafluoroethylene, polyurethane, polyester 10-20% polymer by weight selected from the group of polypropylene, polyethylene, silicone, and PU, 80-90% HFIP by weight, and 0.05-1% rapamycin, taxol and warfarin by weight of polymer. Pushing the liquid containing a drug selected from the group. 32. The method of claim 31, wherein the method comprises rinsing the cloth-like material in a cleaning solution to remove surface drug and then placing the cloth-like material at a target site in vivo. Further comprising a method. The method according to claim 45, rinsing the cloth-like material, deionized water, CO _2, methanol, alcohols, xylene, and the cloth-like material in the wash solution is selected from sterile water A method comprising the step of rinsing. 32. The method of claim 31, wherein the method comprises:
Charging a second spinneret at a potential relative to the predetermined location on the target plate;
The second liquid, including the polymer and solvent, is pushed through the second spinneret, thereby transferring at least some of the potential to the liquid, so that the liquid is in contact with the liquid and the predetermined position. Due to the potential between, forming a flow towards the predetermined location on the target plate, whereby the flow is caused by the potential between the liquid and the predetermined location A method further comprising the step of spreading therein. 32. The method of claim 31, wherein placing the cloth-like material at a target site in vivo comprises wrapping the material around the outer wall of the blood vessel over the region of the blood vessel, A method wherein intimal hyperplasia is prevented. 32. The method of claim 31, wherein a liquid containing a drug is pushed through the spinneret, thereby transferring at least some of the potential to the liquid, so that the liquid and the predetermined position. Forming a flow toward the predetermined position on the target plate, whereby the flow is a plurality of liquids due to the electric potential between the liquid and the predetermined position. Spreading into the plurality of nanofibers, whereby the flow spreads into the plurality of nanofibers due to an electrical potential between the liquid and the predetermined location, the liquid containing the immunosuppressive drug is passed through the spinneret. And thereby moving at least some of the potential to the liquid so that the liquid moves toward the predetermined position on the target plate due to the potential between the liquid and the predetermined position. Flow Forming a, thereby the said stream, due to the potential between the liquid and the predetermined position, spread in a plurality of nanofibers, method.   A material comprising a plurality of randomly oriented internally entangled non-woven microfibers of a first polymer having an average diameter of less than 100 micrometers. 51. The material of claim 50, wherein the microfiber comprises a drug. 52. The material of claim 51, wherein the drug is an immunosuppressant. 53. The material of claim 52, wherein the drug belongs to the group of rapamycin, taxol, and warfarin. 51. The material of claim 50, further comprising a drug trapped between the microfibers and within a gap defined by the microfibers. 51. The material of claim 50, further comprising a plurality of drug-containing microspheres, each microsphere being trapped between the microfibers and within a gap defined by the microfibers. 51. The material of claim 50, wherein the material further comprises a plurality of randomly oriented internally entangled non-woven microfibers of a second polymer having an average diameter of less than 100 micrometers. 51. The material of claim 50, wherein the microfiber comprises a perfluorosulfonate ionomer. The scrim further includes a scrim operatively attached to randomly oriented internally entangled non-woven microfibers of the first polymer so that the scrim is on at least one side of the scrim. 51. The material of claim 50, covered by the microfibers. 51. The material of claim 50, wherein the microfiber further comprises an isotope. 60. The material of claim 59, wherein the isotope comprises thulium oxide ¹⁶⁹ . 60. The material of claim 59, wherein the isotope comprises calcium chloride ⁴⁵ . 51. The material of claim 50, wherein the polymer has a viscosity of 1 to 50 centipoise when in liquid form. A method of delivering radiation to a target site, the method comprising the following steps:
Charging the spinneret with a potential difference relative to a predetermined location on the target plate;
A force is applied to the liquid containing the isotope through the spinneret, thereby transferring at least some of the potential to the liquid, so that the liquid is subjected to a potential difference between the liquid and the predetermined location. Due to forming a flow directed toward the predetermined location on the target plate, whereby the flow is caused by a plurality of potential differences between the liquid and the predetermined location. The process of spreading into nanofibers;
Placing the spinneret at a predetermined distance from the target plate, so that it is sufficiently wet to adhere together when the nanofibers impact the target plate;
Placing the cloth-like material at a target site in vivo;
Orienting electromagnetic energy toward the cloth-like material. 64. The method of claim 63, wherein directing electromagnetic energy toward the cloth-like material is performed prior to placing the cloth-like material at a target site in vivo. 64. The method of claim 63, wherein directing electromagnetic energy toward the cloth-like material is performed after placing the cloth-like material at a target site in vivo. 65. The method of claim 64, wherein directing electromagnetic energy toward the cloth-like material comprises placing the cloth-like material in a nuclear reactor at a predetermined power level for a predetermined period of time. Placing the cloth-like material in the nuclear reactor at a predetermined power level for a predetermined period of time places the cloth-like material in the nuclear reactor at a power level between 1-10 megawatts for 30-60 minutes. 68. The method of claim 66, comprising a step. Placing the cloth-like material in the nuclear reactor at a predetermined power level for a predetermined period of time places the cloth-like material in the nuclear reactor for 40-50 minutes at a power level between 3-7 megawatts. 68. The method of claim 67, comprising a step. Placing the cloth-like material in the nuclear reactor at a predetermined power level for a predetermined time comprises placing the cloth-like material in the nuclear reactor at a power level of about 5 megawatts for about 42 minutes. 68. The method of claim 67, comprising. The cover for the stent:
A plurality of fibers of a first polymer having an average diameter of less than 100 micrometers, adhered to the outer surface of the stent and angled to each other but not woven;
A cover comprising a drug operatively contained within the cover. 71. The stent cover of claim 70, wherein the drug is dissolved in the fiber. 71. The stent cover of claim 70, wherein the drug is contained in a liquid form defined by the fibers and in a gap positioned between the fibers. 71. The stent cover of claim 70, wherein the drug is contained within microspheres in gaps defined by the fibers and positioned between the fibers. A stent:
Body lumen support structure;
A cover disposed on the support structure, comprising a plurality of fibers having an average diameter of less than 100 micrometers, wherein the fibers are a plurality of substantially random gaps in the cover on the support structure. A stent comprising a cover that is aligned in a substantially random pattern to create a space; and a therapeutic agent disposed within the cover. 75. The stent of claim 74, wherein the therapeutic agent is a drug. 75. The stent of claim 74, wherein the therapeutic agent belongs to the group of growth factors and cytokines. 75. The stent of claim 74, wherein the therapeutic agent is a living cell. 75. The stent of claim 74, wherein the therapeutic agent is an anti-restenosis agent. 75. The stent of claim 74, wherein the therapeutic agent is disposed within the interstitial space. 75. The stent of claim 74, wherein at least a portion of the fibers comprise the therapeutic agent. 75. The stent of claim 74, wherein the fibers comprise a polymer. 75. The stent of claim 74, wherein the fiber comprises a polymer and a therapeutic agent. A structure for maintaining the patency of a body lumen comprising:
Support scaffold;
A cover applied to the scaffold, comprising a plurality of nanofibers applied to the scaffold, wherein the nanofibers are substantially wet in order to maximize adhesion to each other and to the scaffold, A cover wherein the fibers have an average diameter less than about 100 micrometers;
A structure comprising a plurality of interstitial spaces in the cover formed by the nanofibers. 84. The structure of claim 83, further comprising a tissue treatment material disposed in at least a portion of the gap space. 85. The structure of claim 84, wherein the tissue treatment substance is an anti-restenosis drug. 84. The structure of claim 83, wherein the nanofiber comprises a polymer. 84. The structure of claim 83, wherein the nanofiber comprises a polymer and a tissue treatment material. A method for maintaining patency of a body lumen, comprising:
Providing a stent frame;
Covering the stent frame with wet fibers, the fibers having a diameter less than 100 micrometers in diameter;
Adhering the wet fibers to each other and to the stent frame so as to produce a cover having a plurality of substantially randomly spaced gap spaces;
Loading the cover with a therapeutic agent;
Introducing the stent frame into a body lumen;
Allowing the therapeutic drug to affect tissue in the body lumen. 90. The method of claim 88, wherein loading the cover with a therapeutic agent comprises covering the stent frame with a polymer and a fiber comprising the agent. 90. The method of claim 88, wherein loading the cover with a therapeutic agent comprises filling at least a portion of the gap space with the agent. 90. The method of claim 88, wherein the step of causing the therapeutic drug to affect tissue comprises allowing dissolution of the drug into the tissue. 92. The method of claim 91, wherein the elution comprises elution of an anti-restenotic drug. 90. The method of claim 88, wherein the covering of the stent frame is performed using electronic spinning. 90. The method of causing the therapeutic drug to affect tissue in the body lumen comprises expanding the stent until the stent contacts tissue in the body lumen. the method of. 95. The method of claim 94, wherein expanding the stent aligns the fibers with a periphery, thereby increasing the radial strength of the cover. A method for controlling the drug release rate of an implantable drug-containing object comprising:
A fibrous fabric having a defined gap between fibers that is small enough to control the rate at which the drug contained by the object can elute into the tissue surrounding the object when the object is implanted A method comprising the step of covering with. A fibrous fabric having a gap defined between fibers that is small enough to control the rate at which the drug contained by the object can elute into the tissue surrounding the object when the object is implanted 99. The method of claim 96, wherein covering with covering comprises covering the object with a polymer fabric having a plurality of fibers having an average diameter of less than 100 micrometers. A fibrous fabric having a gap defined between fibers that is small enough to control the rate at which the drug contained by the object can elute into the tissue surrounding the object when the object is implanted 99. The method of claim 96, wherein the covering step comprises covering the object with a polymer fabric having a plurality of fibers that are angled but not woven with respect to each other. Drug eluting cloth:
An inner layer of fibers having a first average diameter and defining an interstices between the fibers;
A therapeutic agent releasably contained by the inner layer;
An outer layer of fibers of a second average diameter and defining a gap between the fibers that is smaller than the gap in the inner layer such that the release rate of the therapeutic agent is controlled by the gap in the outer layer An outer layer of fibers;
Wherein the outer layer is operably attached to and substantially surrounds the inner layer. 100. The drug eluting fabric of claim 99, wherein the outer layer fibers comprise electrospun fibers having an average diameter of less than 100 micrometers. 100. The drug eluting fabric of claim 99, wherein the fibers of the inner and outer layers comprise electrospun fibers. 102. The drug eluting fabric of claim 101, wherein the first average diameter is greater than the second average diameter. 100. The drug eluting fabric according to claim 99, wherein the outer layer includes a first polymer and the inner layer includes a second polymer different from the first polymer. 100. The drug eluting cloth according to claim 99, wherein the therapeutic agent releasably contained by the inner layer is disposed in at least a part of a gap of the inner layer. 100. The drug-eluting fabric according to claim 99, wherein the therapeutic agent releasably contained by the inner layer is wrapped in a plurality of microspheres, and the microspheres are disposed in at least a part of the gap of the inner layer. Drug eluting cloth. A method of coating an object comprising the following steps:
Covering the object with a layer of fibers defining gaps between the fibers;
Treating the covered object until at least a portion of the gap is reduced;
Including the method. 108. The method of claim 106, wherein covering the object with a layer of the fibers defining the gap between the fibers includes electrospinning a polymer over the objects. 107. The method of claim 106, wherein covering the object with a layer of the fibers defining the gap between the fibers comprises covering the stent with the layer of fibers defining the gap between the fibers. And wherein the stent defines a space, and the layer of fibers includes a bridge portion that extends to cover the space. 107. The method of claim 106, wherein the step of treating the covered object until at least a portion of the gap is reduced comprises treating the covered object until the portion of the gap is reduced. A method comprising the step of heating to a predetermined temperature. 110. The method of claim 109, wherein the step of heating the covered object to a predetermined temperature until at least a portion of the gap is reduced comprises the covering stent for a desired time. Heating to a predetermined temperature until the bridging portion of the layer of material collapses and bonds to the stent. 110. The method of claim 109, wherein the step of heating the covered object at a predetermined temperature until at least a portion of the gap is reduced, wherein the covered object is substantially all of the gap. Heating to a predetermined temperature until reduced. 110. The method of claim 109, wherein the step of heating the covered object at a predetermined temperature until at least a portion of the gap is reduced comprises a predetermined temperature until the fiber melts. Heating to temperature, thereby substantially eliminating all of the gaps. 107. The method of claim 106, wherein the step of treating the covered object until at least a portion of the gap is reduced includes treating the covered material with a solvent until at least a portion of the gap is reduced. A method comprising exposing to a gas atmosphere. A structure for maintaining patency of a body cavity, the structure comprising:
A scaffold structure having sidewalls defining at least one space;
A fibrous coat attached to at least a portion of the scaffold structure but not extending into at least one space of the sidewall;
A structure comprising: 119. The structure of claim 114, wherein the scaffold structure comprises a knitted wire stent. 119. The structure of claim 114, wherein the scaffold structure comprises an unwoven stent.

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