TWI445856B - Electrostatic-assisted fiber spinning method and production of highly aligned and packed hollow fiber assembly and membrane - Google Patents

Description

Electrostatically assisted fiber spinning method and ultrahigh directional and closely arranged hollow fiber group/film manufactured therefrom

The present invention relates to an electrospun fiber group and a method of electrostatically assisted fiber spinning for preparing the fiber group. In particular, the present invention provides an ultra-highly compliant and closely aligned fiber group in which at least 5 fibers are closely packed together and the orientation of the fibers is no greater than +/- 5°, and their preparation and use.

There is a need for biomedical materials (preferably, biocompatible and biodegradable structural matrices) that promote tissue infiltration to repair/regenerate rickets or damaged tissue. Tissue engineering involves the development of a new generation of biological materials that can interact specifically with biological tissues to obtain functional tissue equivalents. Due to extreme conditions of the manufacturing process, such as high or low temperatures, most architectures can only introduce cells and/or signals after the architecture is completed. Seeding cells in the inner portion of the architecture can be difficult, especially for larger objects with fine structural features. This can be very beneficial if the cells can be introduced into the architecture in an in situ manner. Furthermore, the addition of chemical cue, such as growth factors, can be achieved in a controlled manner by fine-tuning the degradation mechanisms of biodegradable polymers such as collagen, polylactic acid and PCL.

It is known that nanotubes and nanofibers having a core sheath, hollow or porous structure have many promising applications in a variety of technologies including, for example, biomedical materials, architecture and tissue regeneration and filtration. These fibers exhibit a particularly advantageous combination of lightweight, flexible, permeable, strong and resilient properties in linear, two-dimensional and three-dimensional structures. In the case of biomedical applications, there is great interest in designing an architectural structure for simulating tissue for better tissue regeneration. The best representation of ultra-high directional structures is the structure of nerves, blood vessels, and some other tissues or parts thereof.

Electrospinning is a process in which a charge droplet is deformed into a superfine fiber by a small droplet of a polymerization solution ejected from a nozzle tip. Electrospinning makes it relatively easy to spin continuous nanofibers from many different materials, including but not limited to polymers. Electrospinning provides a straightforward and practical way to make fibers having diameters ranging from a few nanometers to about two thousand nanometers. Electrospinning is a versatile, low cost process for making micron to nanofibers in film or 3-D form. A device for preparing electrospun nanofibers is described in Polym Int 56: 1361-1366, 2007. WO 2005095684 relates to substantially continuous fibers having a core-and-shell structure; however, such fibers are randomly arranged, non-directed and closely packed. Currently, there are only a few reports on the manufacture of ultra-high-steer electrospun fibers, which are achieved by collecting fibers using the following: rotating discs (A. Theron, E. Zussmanl and AL Yarin 2001) "Electrostatic field-assisted alignment of electrospun nanofibres" (Nanotechnology, Vol. 12, pp. 384-390)), Drums (P. Katta, M. Alessandro, RD Ramsier and GG Chase, 2004, "Continuous Electrospinning of Aligned Polymer" Nanofibers onto a Wire Drum Collector" (Nano Lett, Vol. 4, No. 11), or framework (H. Fong, WD. Liu, CS. Wang, RA. Vaia, 2002, "Generation of electrospun fibers of nylon 6" And nylon 6-montmorillonite nanocomposite" (Polymer, 43(3), pp. 775-780); or the fabrication is achieved by collecting fibers using one of the following: a set of parallel conductive substrates (Dan Li, Yuliang Wang) And Younan Xia's 2003 "Electrospinning of Polymeric and Ceramic Nanofibers as Uniaxially Aligned Arrays" (Nano Lett., Vol. 3, No. 8). A certain degree of fiber orientation by means of multi-domain technology (JM Deitzel, J. Kleinmeyer, JK Hirvonen, Beck TNC. 2001 "Controlled deposition of electrospun poly(ethylene oxide) fibers" (Polymer, Vol. 42, No. 8163 As of 8170 pages)) has also been reported. Furthermore, US 7,575,707 discloses a method for electrospinning nanofibers having a core sheath, tubular or composite structure.

However, all of the above references have the disadvantage of limited directionality, which may become worse as the deposited fibrous layer grows thicker and thicker. The extremely limited manufacturing speed and/or small manufacturing volume of electrospinning with a needle-type spinning head is also annoying, which makes it less industrially valuable.

The report of preparing nano/micro tubes by electrospinning process is a minority. Li et al. have reported the preparation of nanotubes by single capillary electrospinning (Li, XHS, Chang L. and Liu, Yi C. 2007 A Simple Method for Controllable Preparation of Polymer Nanotubes via a Single Capillary Electrospinning. Langmuir (23: pp. 10920 to 10923)). Srivastava has also used fluid-powered fluids to focus on microchannel designs for core/sheath, PPy/PVP and hollow PVP nanofibers (Y. Srivastava, C. Rhodes, M. Marquez, T. Thorsen, 2005 Electrospinning hollow) And core/sheath nanofibers using hydrodynamic fluid focusing; Microfluid Nanofluid, 5: pp. 455-458). Di et al. have calcined the as-spun fibers and the paraffin oil by coaxial electrospinning of the enamel-type-1 nanoparticles in a p-poly(vinylpyrrolidone) (PVP)/ethanol solution. Preparation of zeolite hollow fibers as an internal liquid (J. Di, H. Chen, X. Wang, Y. Zhao, L. Jiang, J. Yu, R. Xu, 2008, Fabrication Hololite Fibers by Coaxial Electrospinning. Chem Mater., 20(11): pp. 3543-3545). However, none of them can prepare microtubes with ultra-high directional and ultra-highly closely aligned. Therefore, there is a need to develop fibers that are structurally oriented and closely aligned.

It is an object of the present invention to provide an ultra-highly compliant and closely aligned fiber group wherein at least five (5) fibers are closely packed together to form a single layer, and the fibers are oriented no more than +/- 5 degrees.

Another object of the present invention is to provide a method of preparing a fiber group of the present invention by electrospinning a polymerization solution, comprising: increasing the weight of the sprayed fiber by adjusting parameters of the electrospinning so that the solution is in solution After the solvent is vaporized, the weight of the resulting fiber is at least 40% of its original weight.

The present invention allows the development of an ultra-highly compliant and closely aligned fiber set that can be used in medical devices such as structures and membranes for tissue regeneration and microchannels.

Although many of the terms, terms, and headings used herein are often used and understood in the context of traditional medical and scientific contexts, the following is a summary description and definition of some terms, as well as a summary of specific names, naming, species names, or titles. Description and definition. These descriptions and definitions are provided to assist in the identification and understanding of the true types and ranges of applications that are intended to be included within the scope of the method of the invention.

As used herein, the term "electrospinning" refers to the technique of making nano-sized fibers (referred to as electrospun fibers) from solution using the interaction between fluid dynamics and charged surfaces. In general, the formation of electrospun fibers involves providing a solution to an orifice in a body in electrical communication with a voltage source, wherein the electrical power assists in the formation of fine fibers that are deposited to be grounded or otherwise at a lower voltage than the body. The voltage on the surface. In electrospinning, a polymerization solution or melt provided from one or more needles, slots or other orifices is charged to a high voltage relative to the collection grid. Power overcomes surface tension and causes the fine jet of polymerization solution or melt to move toward a grounded or oppositely charged collection grid.

As used herein, the term "polymer" means and generally includes, but is not limited to, homopolymers, copolymers (such as block, graft, random and alternating copolymers, terpolymers, etc.) , and blends and variants thereof. Preferably, it may include, but is not limited to, polylactide, polylactic acid, polyolefin, polyacrylonitrile, polyurethane, polycarbonate, polycaprolactone, polyvinyl alcohol (PVA), fiber , polyglucosamine (for example, nylon 6, nylon 406, nylon 6-6, etc.), polystyrene, proteins, and the like, or combinations thereof. Unless specifically limited otherwise, the term "polymer" is intended to include all possible geometric configurations of the material. Such configurations include, but are not limited to, isotactic, syndiotactic, and random symmetry. Solvents suitable for each polymer may be selected from solvents known to those skilled in the art including, but not limited to, sulfuric acid, formic acid, chloroform, tetrahydrofuran, dimethylformamide, water, acetone, and combinations thereof.

As used herein, the term "nano-sized fibers" or "nanofibers" refers to fibers of very small diameter having an average diameter of no greater than about 1500 nanometers (nm). Nanofibers are generally understood to have fiber diameters ranging from about 10 nm to about 1500 nm, more specifically from about 10 nm to about 1000 nm, and more specifically from about 20 nm to about 500 nm, and most specifically It is about 20 nm to about 400 nm. Other exemplary ranges include from about 50 nm to about 500 nm, from about 100 nm to 500 nm, or from about 40 nm to about 200 nm. In the presence of microparticles that are non-uniformly distributed on the nanofibers, known techniques (eg, image analysis tools coupled to electron microscopy) can be used to measure the average diameter of the nanofibers, but exclude There are additional particles and a portion of the fiber that is substantially enlarged relative to the particle free portion of the fiber.

As used herein, the term "oriented fiber" means that substantially all of the fibers in a particular structure or array are configured to be parallel to each other in the longitudinal direction ("unidirectional orientation") or parallel to each other in a well-defined three-dimensional network. ("3D Orientation"). In other words, the fibers are not spatially arranged relative to one another. In most cases, the fibers described herein grow in a generally perpendicular direction relative to the surface of the support substrate, and there is minimal, if any, branching of individual fiber tows.

As used herein, the term "single material layer" or "single layer material" refers to a material composed of a single layer of varying thickness.

As used herein, the term "plurality of layers" or "multilayer material" refers to a "stack" of single layer materials.

Ultra-highly oriented and closely aligned fiber groups

In one aspect, the present invention provides an ultra-highly compliant and closely aligned fiber group wherein at least five (5) fibers are closely packed together to form a single layer, and the fibers are oriented no more than +/- 5 degrees. According to the invention, the fibers can be hollow or solid. Preferably, the fibers are hollow.

The number of fibers closely aligned in the fiber group and the orientation angle of the fibers indicate the degree of tight alignment and the degree of forward direction, respectively. A larger number of fibers means a larger tightly packed density, while a smaller orientation angle shows the degree of directionality of the electrospun fibers. In one embodiment, at least five (5) fibers of the fiber group are closely packed together; preferably, at least 20 fibers are closely packed together; more preferably, at least 50 fibers are closely packed together; Preferably, at least 100 or 200 fibers are closely packed together. In further embodiments, the number of fibers closely aligned together in the fiber group is in the range of 5 to 200, 10 to 200, 20 to 200, 20 to 100, 50 to 200, or 50 to 100.

In another embodiment, the fiber orientation in the fiber group is no greater than +/- 5°; preferably, no greater than +/- 4°; more preferably, no greater than +/- 2°; optimally, no Greater than +/- 1°. In an additional embodiment, the fibers in the fiber group are oriented from about +/- 1[deg.] to about +/- 5[deg.], and more preferably from about +/- 1[deg.] to about +/- 4[deg.].

The length to diameter (outer diameter) ratio (L/d) of the fiber is another parameter of the tight packing density of the fibers. According to another embodiment of the invention, L/d is greater than about 20. Preferably, L/d is greater than about 100, more preferably greater than about 1,000, and most preferably greater than about 10,000. In one embodiment of the invention, the L/d is from about 20 to about 10,000. Preferably, the ratio is from about 20 to 1,000, and more preferably from about 20 to about 100.

The fibers in the fiber group prepared according to the present invention are hollow. The fiber diameter is not an essential characteristic of the present invention. The fibers in the fiber group have an average inner diameter of from about 1 μm (micrometers) to about 100 μm (micrometers). More preferably, the average diameter is from about 10 μm to about 50 μm or from about 15 μm to about 25 μm. Most preferably, the average diameter is about 20 +/- 2 μm. The average wall thickness of the fibers is from about 0.1 μm to about 10 μm. More preferably, the average wall thickness is from about 1 μm to about 5 μm. Most preferably, the average wall thickness is about 3 μm.

Any suitable polymer can be used in the preparation of the fibers of the present invention in accordance with the present invention. Examples of polymers include, but are not limited to: ethylene oxide; polyethylene oxide (PEO); ethylene glycol; polyethylene glycol (PEG); poly(lactic acid) (PLA); poly(glycolic acid) (PGA) Polyethylene oxide (PEO); nylon; polyester; polyamine; poly(proline); polyimine; polyether; polyketone; polyurethane; Polyacrylonitrile; aromatic polyamine; conjugated polymer, such as electroluminescent polymer; poly(2-methoxy, 5-ethyl(2'hexyloxy)-p-phenylene vinyl) MEH-PPV); polystyrene-based; poly-aryl-vinyl group; polythiophene-vinyl group; polypyrrolo-vinyl group; polyhexene-vinyl group; polyaniline; Polyphenylene; poly(arylene); polythiophene; polypyrrole; polyheteroaryl; polyphenyl-exetylene; poly(aryl)-exetylene; polythiophene-exetylene; polyheteroaryl Ethylene group; and mixtures thereof.

In one embodiment of the invention useful for preparing hollow fibers useful in medical applications, the polymer is a biodegradable and/or bioabsorbable polymer comprising a compound selected from the group consisting of glycolide, lactide, and dioxygen. A monomer consisting of cyclohexanone, caprolactone, and trimethylene carbonate. The phrase "containing monomer" is intended to mean a polymer made from a specified monomer or containing a specified monomer unit. The polymer can be a homopolymer, a random or block copolymer, or a heteropolymer containing any combination of such monomers. The material can be a random copolymer, a block copolymer, or a blend of homopolymers, copolymers, and/or heteropolymers containing such monomers.

In one embodiment, the biodegradable and/or bioabsorbable polymer comprises a bioabsorbable and biodegradable linear aliphatic polyester, such as polyglycolide (PGA) and random copolymers thereof (B) Lactide-co-lactide) (PGA-co-PLA). The Food and Drug Administration has approved the use of these polymers for surgical applications, including medical sutures and structures for tissue construction. An advantage of such synthetic absorbable materials is their degradability by simple hydrolysis of the ester backbone in an aqueous environment such as body fluids. The degradation products are ultimately metabolized to carbon dioxide and water, or can be excreted via the kidneys. These polymers are very different from cellulose based materials, which are not absorbed by the body.

Other examples of suitable biocompatible polymers are polyhydroxyalkyl methacrylates (including ethyl methacrylate), and hydrogels (such as polyvinylpyrrolidone, polyacrylamide, and the like). Other suitable bioabsorbable materials are biopolymers including collagen, gelatin, alginic acid, chitin, polyglucosamine, fibrin, hyaluronic acid, polydextrose, and polyamino acids. Any combination, copolymer, polymer or blend thereof of the above examples is contemplated in accordance with the present invention. These bioabsorbable materials can be prepared by known methods.

Particularly useful biodegradable polymers include poly-lactide, poly-glycolide, polycaprolactone, polydioxane, and random and block copolymers thereof. Examples of specific polymers include poly D, L-lactide and polylactide-co-glycolide.

In another embodiment, the fibers of the fiber group of the present invention have a core-shell type structure. Preferably, the shell layer is composed of poly-L-lactic acid, poly(lactic-co-glycolic acid) or a mixture thereof, and the core layer is made of polyethylene glycol, polyethylene oxide, PF127 or contains two or two kinds. A mixture of the above components is constituted.

The present invention provides "epitaxial growth-like" ultra-highly oriented and closely aligned fibers. According to the invention, the fibers of the invention are oriented fibers. In one embodiment of the invention, more than 98% of the fibers have an orientation angle of no more than +/- 5°, and more than 80% of the fibers have an orientation angle in the range of 0° to +/- 2°.

Manufacture of ultra-high alignment and closely aligned hollow fiber groups

The fiber group of the present invention can be produced by electrostatically assisted fiber spinning including, but not limited to, wet spinning, dry spinning, electrospinning, and the like. Preferably, the fiber group of the present invention is produced by electrospinning. More preferably, the fibers are formed by using a two-fluid electrospinning head.

In another aspect, the present invention provides a method of preparing a fiber group of the present invention by electrospinning a polymerization solution, comprising: increasing a weight of the sprayed fiber by adjusting parameters of the electrospinning After the solvent in the solution is vaporized, the weight of the resulting fiber is at least 40% of its original weight. Preferably, the weight of the resulting fiber after evaporation of the solvent in the solution is at least 50% of its original weight. More preferably, the weight of the resulting fiber after evaporation of the solvent in the solution is from 40% to 95% of its original weight. More preferably, after the solvent in the solution is vaporized, the weight of the resulting fiber is 40% to 95%, 40% to 90%, 45% to 90%, 50% to 90%, 40% to 80% of its original weight. Or 50% to 80%. Preferably, the method of the present invention is characterized in that the first polymerization solution (shell solution) as a shell is coaxially electrospun around a second fiber solution (core solution) as a core.

According to the present invention, the weight of the manufactured fiber can be controlled mainly by adjusting the flow rate and concentration of the solution. Other parameters can be used to collectively control the weight of the fibers produced. Other parameters include, but are not limited to, the voltage of the electrospinning, the type of solvent in the solution, and the distance between the collector and the spinneret. Those skilled in the art will be able to select and/or combine different parameters to achieve a weight of the resulting fiber after vaporization of the solvent in solution of 40% to 95% of its original weight.

It is known in the art that in the electrospinning process, the formation of electrospun fibers can be divided into three stages: (1) the Taylor cone stage; (2) the stable jet stage; (3) Unstable jet flow stage (Polym Int 56: 1361-1366, 2007). In the first stage, the power is balanced with the solution viscosity and surface tension to form a Taylor cone. When the power is greater than the surface tension of the solution, the solution begins to pull out from the Taylor cone and fly toward the ground target. At the first portion of the jet flight phenomenon, the fibers have an initial inertial force and fly in a direction toward a predetermined electric field. However, as the solvent vaporizes, the weight of the jet becomes smaller and smaller, and the charge on the surface of the fiber becomes larger and larger. Not only does the normal force act on the jet stream, but forces in different directions also cause lateral movement of the jet. Therefore, the injected fibers enter an unstable phase. The swinging of these fibers becomes larger and wider and wider. When the jetted fibers are eventually collected on a grounded target, they are all random and have no directional preference (as in most cases of electrospinning). The present invention addresses these problems. In order to obtain the electrospun fibers having the largest forward direction, it is important to collect the electrospun fibers before the electrospun fibers enter an unstable state. The present inventors have unexpectedly discovered that in the case of using the compositions of the present invention and the electrospinning process, the sprayed fibers retain most of the original weight to continue their stabilizing phase, and in one fiber next to the other ( That is, it is collected before entering the unstable phase in the "elevation growth" mode.

In one embodiment of the method of the present invention, coaxial electrospinning is used to electrospin the first polymerization solution as a shell around a second fiber solution as a core. Through this process, the polymerization solution is passed through a coaxial spinneret. In one embodiment, one solution is composed of an organic solvent (preferably, dichloromethane (DCM)) having a high vaporization rate as an outer layer, and the other solution may be a non-organic solvent that is transported through the inner core. (such as water). After leaving the spinneret, a Taylor cone is formed by applying a voltage. As the voltage increases, the solution begins to eject toward the grounded collector. During the early stages of spraying (as in most electrospinning processes), the solvent of the outer layer rapidly vaporizes, leaving the solidified skin of the polymer. However, the inner layer solvent has no chance of vaporization and is contained inside the sprayed fibers. In such cases, the weight of the fiber remains at 50% or 60% of its original weight, and the initial inertial force remains the dominant factor, thereby maintaining the fiber to move steadily over its original trajectory. By means of a rotating drum-like collector, the fibers are collected at the same point, which causes the fibers to overlap each other in the direction of rotation. This situation is very similar to the epitaxial growth of some semiconductor materials such as GaAs/AlAs, CdSe/CdS, GaN, and ZnO. Finally, the internal solution is rinsed away leaving ultra-highly closely packed and compliant hollow fibers.

For example, the concentration of the shell solution is in the range of 6% to 25% (w/v). Preferably, the concentration of the first solution is in the range of 13% to 20% (w/v), more preferably in the range of 13% to 19% (w/v), and most preferably 15%. To the range of 19%. Preferably, the first solution and the second solution contain one or more polymers (preferably, biodegradable polymers).

In a further embodiment, the core solution has a flow rate of from 2 ml/hr to 20 ml/hr, preferably from 4 ml/hr to 12 ml/hr.

According to the present invention, hollow fibers are formed by rinsing off the core using a suitable solvent. For example, an aqueous solvent is used to remove the water soluble polymer component, while an organic solvent is used to remove the water insoluble polymer component.

In Figure 1, a schematic view of a coaxial electrospinning arrangement with a drum collection unit is shown. An electrospinning setup suitable for practicing the methods described herein is shown. The electrospinning arrangement comprises a coaxial spinning head having an inner tube and an outer tube. The core solution flows into the inner tube and the shell solution 6 flows into the outer tube. A voltage charger generator is connected to the coaxial spinneret to verify the voltage. The Taylor cone is also shown in the figure.

According to the present invention, the applied voltage is not less than 10 kV to induce the jet of the first solution and the second solution to travel from the coaxial spinneret to the collector at a rotational speed of 50 m/min to 60 m/min. To form a fiber group. The core solution flow rates of the two systems are comparable to the shell solution flow rate. The nature of the solution (viscosity, conductivity and surface tension) needs to be within the general range specified above. All solutions are polymers in solvent form. Specific processing conditions are detailed in the examples. Each of the solutions is delivered as a core fluid or shell fluid to the two fluid coaxial electrospinning head at an appropriate flow rate. The voltage applied to the spinneret will not pull the fluid too quickly or too slowly at the nozzle. The obtained fiber was inspected by photographing a fiber image using an electron microscope.

application

The ultra-highly compliant and closely aligned fiber groups of the present invention can be used in a variety of applications. For example, a solid fiber group can be used as a solid carrier or an insulating material. Hollow fiber groups can be used in biotechnology. For different applications including medical tissue engineering (such as architecture, nerve guiding tubing and vascular catheters) and filtration units, the ultra-highly compliant and closely aligned hollow fiber sets of the present invention can be prepared in a variety of shapes. For example, the ultrahigh compliant and closely aligned hollow fiber groups of the present invention can be rolled into a catheter having a tube-in-tube structure that can be used as a nerve guiding tube. Additionally, the fiber groups can be stacked to form a filter membrane.

In one embodiment, the ultra-highly compliant and closely aligned hollow fiber set of the present invention for use as a medical device/architecture can be seeded in situ with cells, thereby allowing the cells to be suspended in the architecture and exposed to a 3-D form. Appropriate molecular inserts. These cell-inoculated hollow fiber groups can be used in tissue replacement protocols. According to this embodiment, the tissue can be restored in a test tube and then the tissue is implanted into its host in distress. Useful cells include nerve cells, epithelial cells, endothelial cells, fibroblasts, myoblasts, chondroblasts, osteoblasts, and neural stem cells. Other cells useful in the methods and groups of fibers of the invention include Schwann cells (WO 92/03536), astrocytes, oligodendrocyte glial cells and precursors thereof, adrenal chromaffin cells, and analog.

In another embodiment, the fiber group of the present invention can be formed into a porous film used as a microfiltration membrane for filtration, more specifically, a porous water filtration membrane in the form of a hollow fiber.

Instance

Example 1 electrospinning process

The materials used to make the hollow fiber group are poly-L-lactic acid (PLLA; Mw = 140000 Da, Japan), polyethylene glycol (PEG; Mw = 35000 Da, Sigma-Aldrich), polyethylene oxide (PEO; Mw = 900000 Da, Sigma-Aldrich), and the solvent of dichloromethane (DCM; Mallinckrodt, USA) and N,N-dimethylformamide was purchased from Sigma-Aldrich, Inc. (St. Louis, MO). These polymers and solvents for electrospinning were used as they were without further purification.

The outer shell of the PLLA solution varies from 12% (wt/vol) to 20% (wt/vol) in a 9:1 ratio of dichloromethane (DCM) to N,N-dimethylformamide (DMF). (12%, 15%, 17% and 20%). An aqueous PEG/PEO (weight ratio = 1:1) solution was obtained by dissolving in 10% (wt/vol) of re-distilled water. Transfer the PEG/PEO solution to the inner core. The electrospinning parameters used to obtain PLLA/PEG-PEO shell-core fibers are as follows: 6 cm gap distance, 14.6 kV applied voltage, 5 mL/h internal flow rate, 6 mL/h external flow rate, 58.5 The collection rate of m/s, relative humidity of about 68%, and at room temperature (about 25 ° C).

After using a rotary collector at a rate of 58.5 m/s, PLLA/PEG-PEO shell-core fibers were collected as ultra-high directional fibrous membranes. The higher the concentration of PLLA, the higher the forward direction. After the PLLA/PEG-PEO shell-core fibers were cut into film fragments, they were placed in re-distilled water for 24 hr, and the inner core PEO-PEG fibers were dissolved, followed by the manufacture of ultra-high electrospun hollow fibers.

Example 2 Preparation of the fiber group of the present invention

A coaxial spinneret connected to a high voltage power source is used as a material dispenser. The two polymerization solutions (PLLA in dichloromethane, wt/vol. 17%; and PEG/PEO 50/ in deionized distilled water) were injected by a syringe pump at a rate of 5 ml/hr and 4 ml/hr, respectively. 50, wt/vol. is 10%) individually twitched to the outer tube and inner tube of the coaxial spinning head. After applying a high voltage of 14.6 kV, the polymerization solution was ejected from the spinneret, and the electrospun fibers were collected by a rotating metal frame separated by 6 cm. The collection frame was rotated at 58.5 m/s. This operation was carried out at a relative humidity of 68% at a temperature of 25 °C. The resulting fibers collected on a metal frame are shown in FIG. These fibers are collected over a very narrow range as compared to the randomly expanded pattern of commonly collected electrospun fibers. As the operating time becomes longer and longer, these fibers accumulate over this extremely narrow range and are ultimately upright and perpendicular to the surface of the collection unit, as seen in Figure 3. The fibers are then rinsed with water to remove the water soluble components such that a hollow structure is formed. After inspection using scanning electron microscopy, a large area of the contiguous tube sheet was observed, as shown in FIG. Remarkably, these fibers are perfectly attached in a manner never before seen, as shown in Figure 5. They are attached one by one and forward to form a sheet having a single fiber thickness. The height of the erect membrane can reach 2 cm to 3 cm (1 cm in this case) in less than twenty minutes, with a deposition width of only 3 mm to 4 mm, as shown in Figures 4 and 5. The cross-sectional view shows that the fibers are closely aligned one by one while still having the integrity of the hollow structure, as shown in Figures 6 and 7. This perfection of electrospinning fibers has never been reported in previous studies. The size of these fibers was determined by image analysis software ImageJ. It has been found that these hollow fibers have an average inner diameter of 19 ± 1.5 microns with a wall thickness of a few microns. The wall of the hollow fiber is solid, as shown in Figure 8.

Example 3 Preparation of the fiber group of the present invention

A coaxial spinneret connected to a high voltage power source is used as a material dispenser. The two polymerization solutions (PLGA in dichloromethane, wt/vol 17%; and PEG/PEO in deionized distilled water, wt/ by syringe pump, respectively, at a rate of 5 ml/hr and 4 ml/hr The vol is 10%) individually twitched to the outer and inner tubes. After applying a high voltage of 14.6 kV, the polymerization solution was ejected from the spinneret, and the electrospun fibers were collected by a rotating metal frame separated by 6 cm. The collection frame was rotated at 58.5 m/s. This operation was carried out at a relative humidity of 68% at a temperature of 25 °C. The electrospun fibers were studied by SEM as shown in FIG.

Example 4 Preparation of the fiber group of the present invention

A coaxial spinneret connected to a high voltage power source is used as a material dispenser. The two polymerization solutions were separately pumped at a rate of 5 ml/hr and 4 ml/hr by a syringe pump (DCM/DMF: PLLA/PF127 in 9/1, "60/40 by weight", l7 wt %; and PEG/PEO in deionized distilled water: 50/50, 10 wt%). After applying a high voltage of 14.6 kV, the polymerization solution was ejected from the spinneret, and the electrospun fibers were collected by a rotating metal frame 10 cm apart. The collection frame was rotated at 58.5 m/s. This operation was carried out at a relative humidity of 68% at a temperature of 25 °C. After rinsing by deionized distilled water to remove the water soluble component, the resulting film not only reveals the hollow fibers, but also reveals the porous wall structure, as shown in FIG. A high orientation is achieved, as shown in Figure 11; however, it is not as obvious as in the previous situation. The diameter of the hollow fibers is in the range of tens of microns, wherein the wall thickness is a few microns. The porous wall structure was characterized by ImageJ software, and the pore size was found to be in the range of submicron to several micrometers. Initial penetration testing confirmed the continuity of the micropores in the wall. It was also examined that these porous hollow fibers can easily penetrate the liquid. Figures 12 and 13 are SEMs of electrospun fibers obtained from similar compositions having the same operating parameters.

Example 5 Using a polymerization solution having various concentrations to prepare the fiber group of the present invention

Materials and methods were similar to those of Example 1 and only changed the concentration of the PLLA solution. By using a shell PLLA solution having a concentration of 6 wt%, 8 wt%, 10 wt%, 15 wt%, 17 wt%, and 19 wt% of PLLA, it has been observed that when the solution has 6 wt% to 10 wt% At lower concentrations, the collected fiber groups are scattered around the surface of the collecting drum. At higher concentrations (15% to 16%), these fibers begin to concentrate to very narrow points and eventually stand up when the flow rate ratio reaches 17% and 19%, as shown in Figure 14. Figure 15 shows SEM images of PLLA hollow fiber membranes prepared from different concentrations: (a) 8 wt%; (b) 12 wt%; (c) 15 wt%; (d) 16 wt%; (e) 17 wt%; and (f) 19 wt%. As the concentration increases, the fibers exhibit a better forward and tighter alignment. At a concentration of 19 wt%, the PLLA electrospun hollow fiber group has the highest orientation, as shown in FIG.

Example 6 uses a polymerization solution having various flow rates to prepare the fiber group of the present invention.

The materials and methods are similar to those of Example 1 in which only the flow rate of the internal solution is varied. The internal flow rate of the PEO solution was increased from 5 ml/hr to 12 ml/hr by using an 8 w/v% PLLA solution as the shell material and delivering the solution at a constant flow rate of 5 ml/hr. It has been observed that when the flow rate ratio is low (i.e., 1 ml/hr to 1.6 ml/hr), the collected fiber groups are scattered around the surface of the collecting drum. At higher flow rate ratios (1.8 ml/hr to 2.0 ml/hr), these fibers begin to concentrate to very narrow points and eventually stand up when the flow rate ratio is 2.2 and 2.4, as shown in Figure 17. As the internal flow rate increases, the fibers also exhibit a better forward and tighter alignment. As shown in Figure 18, Figure 18 provides an SEM image of the PLLA hollow fiber membrane prepared from the following different flow rate ratios: (a) 1.2 Ml/hr; (b) 1.6 ml/hr; (c) 2.0 ml/hr; and (d) 2.4 ml/hr. As shown in Fig. 19, the PLLA electrospun hollow fiber group has the highest orientation at a flow rate ratio of 2.4 ml/hr.

Example 7 uses a polymerization solution having various flow rates in combination with various voltages to prepare the fiber group of the present invention.

Figure 20 provides an operational diagram of factors that affect the applied voltage and weight of the spun fiber. A series of solutions with different PLLA concentrations (8 wt%, 10 wt%, 12 wt%, 15 wt%, 17 wt%, and 19 wt%) were subjected to an increase in field strength from 0 kV/cm to 4 kV/cm. . The field strength at which the fiber is pulled from the Taylor cone is recorded as the lower critical limit. When the field strength is too high to cause the fiber to collapse or cause significant oscillation, the field strength is marked as the upper limit field strength limit. This figure shows the three regions separated by the upper and lower voltage limits (see Figure 20). An example spinning condition is described below. Under the spinning condition of 15 wt% PLLA solution and 15 kV voltage, as the voltage increases, the spun fiber starts to pull from the Taylor cone on the right side of the spinneret. When the voltage reaches the critical value, the fiber will be sprayed toward the ground. end. First, the flying fibers move toward the grounded target. At the beginning, in zone I, the solution viscosity is large enough to prevent the solution from being pulled by a smaller electrostatic force. As the voltage increases and reaches a critical value, in region II, the fibers are continuously formed and fly toward the ground target. The tight alignment of these fibers and the growth of the erect membranes are made possible by the power and the residual weight of the fibers. However, as the voltage continuously increases, in region III, the electric power becomes dominant, causing the fiber to oscillate (sometimes causing a random expansion of the main jetted solution). As indicated by Fig. 21, the lower limit threshold voltage for film formation is also in the same tendency as the lower limit threshold voltage of the solution viscosity. It should be noted that the formation of fibers in the early stages is fairly easy to achieve from the spinneret (such as 8 wt% to 12 wt%), however, it may be excellent only in the case of applying some static electricity (even at very low voltages). Tightly arranged. This operational diagram provides a useful guide for making ultra-high compliant and closely aligned membranes.

Example 8 cell viability assay

Primary caries were obtained from the Center of Taipei Medical Teeth Bank and Dental Stem Cell Technology. The pulp was extracted from the resected teeth, and the pulp was mechanically minced and the pulp was treated with 0.25% trypsin-EDTA (Invitrogen, Carlsbad, CA) at 37 ° C for 15 min. A pipette was used to wet the resulting mixture of dental pulp cells. After treating the discrete cells for 15 min at 37 °C with an equal volume of 0.5 mg/mL trypsin inhibitor (Invitrogen) and 2000 U/mL DNase I (Sigma, St. Louis, MO), The pulp suspension was centrifuged at 1500 rpm for 5 min and the supernatant was discarded.

In order to test the biocompatibility of PLLA electrospun hollow fiber groups, the ISO 10993 standard procedure was followed (Sasaki, R. et al. 2008 Tubulation with dental pulp cells promotes facial nerve regeneration in rats. Tissue Engineering-Part A. ( 14(7): pp. 1141-1147)), and the DPSC is incubated for 6 days in the PLLA architecture. The results show that cell viability is close to cell viability of the control cohort, suggesting no cytotoxicity, as shown in Figure 22.

1 shows a schematic view of an electrospinning having a coaxial electrospinning arrangement of a drum collection unit that is adapted to practice the method of the present invention.

Figure 2 shows the physical appearance of the "erect" fibers of the present invention collected on a rotary collector of the present invention.

Figure 3 shows (a) side view and (b) top view of the collected upright PLLA fibrous film.

Figure 4 shows a large area of ultra-high forward and closely aligned hollow PLLA hollow fibers.

Figure 5 shows ultra-high forward and closely aligned hollow PLLA fibers (details).

Figure 6 shows SEM photography (showing both cross-section and surface) of ultra-high forward and closely aligned PLLA hollow fibers.

Figure 7 shows an ultra-highly compliant and closely aligned electrospun PLLA hollow fiber (detailed in cross section).

Figure 8 shows an SEM photograph of a cross-sectional view of an electrospun PLLA hollow fiber with solid walls.

Figure 9 shows SEM photography of a cross-sectional view of an electrospun PLGA hollow fiber.

Figure 10 shows an SEM photograph (top view) of an electrospun PLLA hollow fiber having a porous wall.

Figure 11 shows an SEM photograph (cross-sectional view) of an electrospun PLLA hollow fiber having a porous wall.

Figure 12 shows SEM photography (details) of electrospun PLLA hollow fibers with porous walls.

Figure 13 shows SEM photography of electrospun PLLA hollow fibers with porous walls.

Figure 14 shows the physical appearance of collected electrospun PLLA hollow fibers prepared from different concentrations: (a) 6 wt%; (b) 8 wt%; (c) 15 wt%; and (d) 19 wt %.

Figure 15 shows SEM images (at 300 magnifications) of PLLA hollow fiber membranes prepared from different concentrations: (a) 8 wt%; (b) 12 wt%; (c) 15 wt%; d) 16 wt%; (e) 17 wt%; and (f) 19 wt%. Samples were collected over a 20 second period.

Figure 16 shows the fiber orientation of PLLA hollow fiber membranes prepared from various concentrations.

Figure 17 shows the physical appearance of the collected electrospun PLLA hollow fibers prepared from the following different flow rate ratios: (a) 1.2 ml/hr; (b) 1.6 ml/hr; (c) 2.0 ml/hr; (d) 2.4 ml/hr.

Figure 18 shows an SEM image of PLLA hollow fiber membranes prepared at different FRR _(i/o) (at 300 magnifications): (a) 1; (b) 1.4; (c) 1.8; ) 2.0; (e) 2.2; and (f) 2.4. Samples were collected over a 20 second period.

Figure 19 shows the fiber orientation of PLLA hollow fiber membranes prepared from different flow rate ratios (flow in/out).

Figure 20 shows an operational diagram of the factors of the applied voltage and weight of the focused spun fiber.

Figure 21 shows the relationship between the concentration of the polymerization solution and the viscosity of the solution.

Figure 22 shows cell viability of the control group and DPSC in the PLLA group (n=9).

(no component symbol description)

Claims (34)

An ultrahighly compliant and closely aligned electrospinning group in which at least five (5) electrospun fibers are closely packed together to form a single layer, and the orientation of the electrospun fibers relative to the long axis of the fiber group Not more than +/- 5°; wherein the electrospun fibers are joined by electrostatic forces such that the electrospun fibers are closely packed together to form a single layer, and wherein the fibers are aligned in a straight line no greater than +/- 5°. The fiber group of claim 1, wherein at least 20 of the fibers are closely packed together to form a single layer. A fiber group according to claim 1, wherein at least 50 fibers are closely arranged together to form a single layer. The fiber group of claim 1, wherein the number of the fibers closely aligned in the fiber group is in the range of 5 to 200. The fiber group of claim 1 wherein the orientation of the fibers is no greater than +/- 2°. The fiber group of claim 1 wherein the orientation of the fibers is from about +/- 1° to about +/- 5°. The fiber group of claim 1, wherein the orientation of the fibers is from about +/- 1[deg.] to about +/- 4[deg.]. The fiber group of claim 1, wherein the fibers are hollow. The fiber group of claim 1, wherein the L/d is from about 20 to about 10,000. The fiber group of claim 1, wherein the fibers of the fiber group have an average inner diameter of from about 1 μm (micrometer) to about 100 μm (micrometer). The fiber group of claim 1, wherein the average diameter is from about 10 μm to about 50 Mm. The fiber group of claim 1, wherein the average diameter is from about 15 μm to about 25 μm. The fiber group of claim 1, wherein the average diameter is about 20 +/- 2 μm. The fiber group of claim 1, wherein the fibers have an average wall thickness of from about 0.1 μm to about 10 μm. The fiber group of claim 1, wherein the average wall thickness is from about 1 μm to about 5 μm. The fiber group of claim 1, wherein the fiber group is composed of a polymer selected from the group consisting of ethylene oxide; polyethylene oxide; ethylene glycol; polyethylene glycol; poly(lactic acid) (PLA); poly(glycolic acid) (PGA); poly(ethylene oxide) (PEO); nylon; polyester; polyamine; poly(amino acid); polyimine; polyether; polyketone; Polyurethane; polycaprolactone; polyacrylonitrile; aromatic polyamine; conjugated polymer, such as electroluminescent polymer; poly(2-methoxy, 5 ethyl (2') Oxyl)p-phenylenevinyl)(MEH-PPV);polyphenylenevinyl;polyaryl-vinyl;polythiophene-vinyl;polypyrrole-vinyl;poly Heteroaryl-stretched vinyl; polyaniline; polyphenylene; poly(arylene); polythiophene; polypyrrole; polyheteroaryl; polyphenyl-exetylene; poly(aryl)-exetylene; polythiophene Anthracene-extended ethynyl; poly(extended heteroaryl-extended ethynyl); and mixtures thereof. The fiber group of claim 1, wherein the fiber group is composed of a polymer selected from the group consisting of: glycolide; lactide; dioxanone; caprolactone; and triethylene carbonate ester. The fiber group of claim 1, wherein the fiber group is composed of a polymer selected from the group consisting of poly-lactide; poly-glycolide; polycaprolactone; polydioxane; Poly D, L-lactide; and polylactide-co-glycolide. The fiber group of claim 1 can be used in medical tissue engineering and filtration units. The fiber group of claim 19, wherein the medical tissue engineering comprises a framework, a nerve guiding conduit, and a vascular catheter. As in the fiber group of claim 1, it can be inoculated with cells in situ. The fiber group of claim 21, wherein the cell lines are selected from the group consisting of: a nerve cell; an epithelial cell; an endothelial cell; a fibroblast; a myoblast; a chondroblast; an osteoblast; a neural stem cell ; nerve sheath cells; astrocytes; oligodendrocyte glial cells and their precursors; adrenal chromaffin cells; and mixtures thereof. A method for preparing a fiber group of the present invention by electrospinning a polymerization solution, comprising: increasing a weight of the sprayed fiber by adjusting parameters of the electrospinning, such that after the solvent in the solution is vaporized, The weight of the resulting fiber is at least 40% of its original weight. The method of claim 23, wherein the method is characterized in that the first polymerization solution (shell solution) as a shell is coaxially electrospun around a second fiber solution (core solution) as a core. The method of claim 24, wherein the first solution and the second solution comprise one or more biodegradable polymers. The method of claim 24, further comprising the step of: rushing Washing to remove the core to form hollow fibers. The method of claim 23, wherein the weight of the produced fiber can be controlled by adjusting the voltage of the electrospinning or the flow rate of the solution. The method of claim 23, wherein the weight of the produced fiber can be controlled by adjusting the concentration of the electrospinning solution, the type of solvent in the solution, or the distance between the collector and the spinneret. The method of claim 28, wherein the concentration is in the range of 6% to 25% (w/v). The method of claim 28, wherein the concentration is in the range of 13% to 20% (w/v), 13% to 19% (w/v) or 15% to 19%. The method of claim 24, wherein the flow rate of the core solution is from 2 ml/hr to 20 ml/hr. The method of claim 24, wherein the flow rate of the core solution is from 4 ml/hr to 12 ml/hr. The method of claim 23, wherein the weight of the resulting fiber after the solvent is vaporized in the solution is from 40% to 95% of its original weight. The method of claim 23, wherein the weight of the resulting fiber after the solvent is vaporized in the solution is from 40% to 80% of its original weight.