Highly aligned and packed hollow fiber assemblies

Abstract

Provided are highly aligned, densely packed electrospun fiber assemblies, in which the fibers have at least extensions or pores on their surfaces. Microtube array membranes (MTAMs) comprise the fiber assemblies of the invention. Uses of these electrospun fiber assemblies in biological applications and methods for producing these electrospun fiber assemblies are also provided.

Description

[Technical Field]

[0001] The present invention relates to electrospun fibers and fiber arrays having nanoscale hair-like bi-layer or alternating layer structures. [Background technology]

[0002] Electrospinning is an established technique used to fabricate nonwoven fiber mats for a variety of applications, including drug delivery vehicles, tissue engineering scaffolds, nanofiltration membranes, and battery materials. Electrospinning is a process that relies on an electric charge to transform conical droplets of polymer solution ejected from a nozzle tip into ultrafine fibers. Electrospinning makes it relatively easy to spin continuous nanofibers from many different materials, including but not limited to polymers. Electrospinning offers a straightforward and practical method for producing fibers with diameters ranging from a few nanometers to approximately 2,000 nanometers. Electrospinning offers a versatile, low-cost method for fabricating micron- to nanoscale fibers in the form of either membranes or 3D structures.

[0003] WO2005095684 is directed to substantially continuous fibers with a core-sheath structure, but these fibers are randomly arranged and not aligned or packed. US9,713,521B2 relates to a highly aligned, densely packed fiber assembly, where at least five fibers are packed together and the fiber orientation is + / - 5° or less, and its preparation and uses. US20180100249 provides polymer nanofiber or microfiber mats or membranes and a method for preparing them by aqueous, one-step polyelectrolyte complexation and electrospinning of complex coacervates. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] WO2005095684 [Patent Document 2] US9,713,521B2 [Patent Document 3] US20180100249 Summary of the Invention [Problem to be solved by the invention]

[0005] However, there is still a need to improve the surface-to-volume ratio, specific surface area, or porosity of electrospun fibers. [Means for solving the problem]

[0006] The present invention provides a hollow electrospun fiber assembly comprising a plurality of fibers having nanoscale hair-like structures extending from the inner surface thereof.

[0007] In one embodiment, the hair-like structures of the fibers have a length in the range of about 100 nm to about 1 μm. In some further embodiments, the length of the hair-like structures ranges from about 200 nm to about 1 μm, about 300 nm to about 1 μm, about 400 nm to about 1 μm, about 500 nm to about 1 μm, about 600 nm to about 1 μm, about 700 nm to about 1 μm, about 800 nm to about 1 μm, about 900 nm to about 1 μm, about 200 nm to about 900 nm, about 200 nm to about 800 nm, about 200 nm to about 700 nm, about 200 nm to about 600 nm, about 200 nm to about 500 nm, about 200 nm to about 400 nm, about 200 nm to about 300 nm, or about 300 nm to about 1 μm. m, about 300 nm to about 900 nm, about 300 nm to about 800 nm, about 300 nm to about 700 nm, about 300 nm to about 600 nm, about 300 nm to about 500 nm, about 300 nm to about 400 nm, about 400 nm to about 1 μm, about 400 nm to about 900 nm, about 400 nm to about 800 nm, about 400 nm to about 700 nm, about 400 nm to about 600 nm, about 500 nm to about 1 μm, about 500 nm to about 900 nm, about 500 nm to about 800 nm, about 500 nm to about 700 nm, or about 500 nm to about 600 nm.

[0008] In one embodiment, the hair-like structures have an aspect ratio (or L / d ratio) of up to 20:1. In some embodiments, the hair-like structures have an aspect ratio of up to 15:1, or up to 10:1. In other embodiments, the hair-like structures have an aspect ratio of at least 1:1, at least 3:1, or at least 5:1. The aspect ratio falls within a reasonable range having the endpoints noted above. Some specific embodiments of aspect ratios include, but are not limited to, 1:1 to 20:1. In one embodiment, the surface coverage of the hair-like structures is about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, about 40% to about 80%, about 40% to about 70%, about 50% to about 80%, or about 60% to about 80%.

[0009] In some embodiments, the pores on the surface of the fiber have a size ranging from about 5 nm to about 1 μm. In some embodiments, the pore size ranges from about 20 nm to about 500 nm, about 20 nm to about 400 nm, about 20 nm to about 300 nm, about 20 nm to about 200 nm, about 20 nm to about 100 nm, about 20 nm to about 80 nm, about 20 nm to about 70 nm, or about 20 nm to about 60 nm. The density of pores on the surface ranges from about 0.1% to about 30%. In some embodiments, the density is about 0.1% to about 25%, about 0.1% to about 20%, about 0.1% to about 15%, about 0.1% to about 10%, about 0.1% to about 5%, about 0.1% to about 15%, about 1% to about 30%, about 1% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 1% to about 5%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 30%, about 15% to about 25%, or about 15% to about 20%.

[0010] In one embodiment, the fiber has a core-sheath structure. Examples of polymers used as the core or sheath solution include ethylene oxide, polyethylene oxide (PEO), ethylene glycol, polyethylene glycol (PEG), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), nylon, polyester, polyamide, poly(amic acid), polyimide, polyether, polyketone, polyurethane, polycaprolactone, polyacrylonitrile, polyaramid, conjugated polymers such as electroluminescent polymers, poly(2-methoxy,5-ethyl ( Polyphenylene vinylenes include, but are not limited to, 2'-hexyloxy)para-phenylene vinylene (MEH-PPV), polyphenylene vinylenes, polyarylene-vinylenes, polythienolene-vinylenes, polypyrrolo-vinylenes, polyheteroarylene-vinylenes, polyanilines, polyphenylenes, polyarylenes, polythiophenes, polypyrroles, polyheteroarylenes, polyphenylene-ethynylenes, polyarylene-ethynylenes, polythieno-ethynylenes, polyheteroarylene-ethynylenes, and mixtures thereof. In some embodiments, the polymer is a biodegradable and / or bioabsorbable polymer, such as polyglycolide (PGA) and its random copolymer poly(glycolide-co-lactide) (PGA-co-PLA), polyhydroxyalkyl methacrylates including ethyl methacrylate, and hydrogels, such as polyvinylpyrrolidone, polyacrylamide, collagen, gelatin, alginate, chitin, chitosan, fibrin, hyaluronic acid, dextran, and polyamino acids, or mixtures thereof. In further embodiments, the solution is a mixture of PLA, PEO, and PEG. In one embodiment, the core is composed of a mixture of PLA, PEO, and PEG.

[0011] In one embodiment, at least 5 fibers are packed together in the fiber assembly, preferably at least 20 fibers, more preferably at least 50 fibers, and most preferably at least 100 or 200 fibers. In further embodiments, the number of fibers packed together in the fiber assembly ranges from 5 to 200, 20 to 200, 10 to 200, 20 to 200, 20 to 100, 50 to 200, or 50 to 100. In one embodiment, the fiber assembly is in the form of a film, membrane, or sheet. In another embodiment, the fiber assembly has a concentric appearance.

[0012] In another embodiment, the orientation of the fibers in the assembly is no more than + / - 5°, preferably no more than + / - 4°, more preferably no more than + / - 2°, and most preferably no more than + / - 1°. In a further embodiment, the orientation of the fibers in the assembly is from about + / - 1° to about + / - 5°, more preferably from about + / - 1° to about + / - 4°.

[0013] According to another embodiment of the present invention, the ratio of length to diameter (outside) of the fiber (L / d) is greater than about 20. Preferably, L / d is greater than about 1.00, more preferably greater than about 1.000, and most preferably greater than about 10.000. In one embodiment of the present invention, L / d is from about 20 to about 10.000. Preferably, this ratio is from about 20 to 1.000, more preferably from about 20 to about 100.

[0014] The present invention also provides a microtube array membrane (MTAM) comprising one or more layers of the hollow electrospun fiber assemblies described herein.

[0015] In one embodiment, the MTAM comprises at least two layers of fiber assemblies. In a further embodiment, the MTAM has a structure in which the layers of fibers are arranged alternately or perpendicularly.

[0016] The present invention also provides a pocket surrounding the MTMA described herein.

[0017] The present invention also provides methods of using the hollow electrospun fiber assemblies or MTAMs of the present invention in drug screening, matrix-format cell culture, fermentation, tissue engineering, drug screening (e.g., cancer drug screening and cancer immunotherapy drug screening), and filtration (e.g., dialysis). [Brief explanation of the drawings]

[0018] [Figure 1] FIG. 1 is an SEM image (cross section) of an embodiment of MTAM-h (with hairy extensions). [Figure 2] FIG. 1 is an SEM image (cross section) of an embodiment of MTAM-p (with sponge-like fibers). [Figure 3] 3(a) and 3(b) are SEM images (cross-section / top view) of an embodiment of MTAM-dl (with a bilayer configuration of fibers). [Figure 4] 4(a) and 4(b) are SEM images (cross section / top view) of an embodiment of MTAM-dl-al (with alternating fiber configuration). [Figure 5] FIG. 1 shows the excellent reproducibility of MTAM-dl-al. [Figure 6] 10 is an SEM image of an embodiment of MTAM-dl-h (having hairy extensions within the two-layer configuration of the fiber). [Figure 7] FIG. 1 shows cell viability for TCP, MTAM, and MTAM-h. [Figure 8] FIG. 1 shows the endotoxin absorption capacity of MTMA and MTMA-h having antibiotics immobilized on their surfaces. [Figure 9] FIG. 1 shows the endotoxin absorption capacity of MTMA-al and Toraymyxin™ having antibiotics immobilized on their surfaces. DETAILED DESCRIPTION OF THE INVENTION

[0019] While many of the words, terms, and headings used herein are commonly used and customarily understood within traditional medical and scientific contexts, a summary explanation and definition of some terms, and of specific names, designations, epithets, or nicknames, is provided below as an aid in appreciating and understanding the variety and scope of applications intended to be encompassed within the scope of the present methodology.

[0020] As used herein, the term "microtube array membrane" (abbreviated "MTMA") refers to a film or membrane composed of one or more layers of aligned, hollow, nano-sized fibers. A suffix added to the term "MTMA" refers to the specific configuration of the array or the surface morphology of the fibers, while a prefix added to the term "MTMA" refers to the material. For example, "MTMA-hairy" means that the fibers of the microtube array membrane have hair-like extensions on the surface of the fibers, "MTMA-al" means that the layers of fibers are arranged alternately in the z-direction, and "PLLA-MTMA" means that the microtube array membrane is made of polylactic acid, etc.

[0021] As used herein, the term "electrospinning" refers to a technique for creating nano-sized fibers, called electrospun fibers, from a solution using the interaction between fluid dynamics and an electrically charged surface. Generally, the formation of electrospun fibers involves supplying a solution to an orifice in a body that is in electrical communication with a voltage source, where electrical forces assist in the formation of thin fibers that are deposited on a surface that is grounded or otherwise at a lower voltage than the body. In electrospinning, a polymer solution or melt, dispensed through one or more needles, slots, or other orifices, is charged to a high voltage relative to a collection grid. The electrical forces overcome surface tension and propel a thin jet of polymer solution or melt toward a grounded or oppositely charged collection grid.

[0022] As used herein, the term "polymer" refers to and generally includes, but is not limited to, homopolymers, copolymers, such as block, graft, random, and alternating copolymers, terpolymers, and the like, as well as blends and modifications thereof. Preferably, the term "polymer" may include, but is not limited to, polyalkylene oxides (e.g., PEO, PPO, PEO / PPO, etc.), polylactides, polylactic acids, polyolefins, polyacrylonitriles, polyurethanes, polycarbonates, polycaprolactones, polyvinyl alcohols (PVA), cellulose, chitosan, nylons (e.g., nylon 6, nylon 406, nylon 6-6, etc.), polystyrenes, 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. These configurations include, but are not limited to, isotactic, syndiotactic, and random symmetries. Suitable solvents for each polymer can 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.

[0023] As used herein, the terms "nano-sized fibers" or "nanofibers" refer to very small diameter fibers having an average diameter of about 1500 nanometers (nm) or less. Nanofibers are generally understood to have a fiber diameter range of about 10 to about 1500 nm, more specifically about 10 to about 1000 nm, even more specifically about 20 to about 500 nm, and most specifically about 20 to about 400 nm. Other exemplary ranges include about 50 to about 500 nm, about 100 to about 500 nm, or about 40 to about 200 nm. When particulates are present and unevenly distributed on the nanofiber, the average diameter of the nanofiber can be measured using known techniques (e.g., image analysis tools coupled with an electron microscope), excluding portions of the fiber that are substantially enlarged by the presence of the added particulates relative to the particle-free portions of the fiber.

[0024] As used herein, the term "oriented fibers" indicates that substantially all fibers in a particular structure or array are arranged parallel to one another in the longitudinal direction ("unidirectionally oriented") or in a well-defined three-dimensional network ("three-dimensionally oriented"). In other words, the fibers are not randomly arranged relative to one another in space. In most cases, the fibers described herein extend in a direction generally perpendicular to the surface of the supporting substrate, with very little, if any, branching of the individual fiber strands.

[0025] As used herein, the terms "single layer of material" or "single layer material" refer to a material that is composed of a single layer that may be of variable thickness.

[0026] As used herein, the terms "multiple layers" or "multi-layer material" refer to a "stack" of single layer material.

[0027] As used herein, the terms "hairy" or "hairy" are used to describe the appearance of extensions from the surface of a fiber, or the overall appearance of the extensions. A "hairy" or "hairy" shape includes at least one filament, string, thread, fibril, hair, etc., made of the material of the fiber and connected to the surface of the fiber.

[0028] The present invention has unexpectedly discovered that the creation of hair-like structures within the lumen of electrospun fibers increases the surface area of ​​the fibers, allowing them to be easily scaled. Accordingly, the present invention provides hollow electrospun fibers, fiber assemblies with a large surface-to-volume ratio, high specific surface area, or interconnected porosity, and microtube array membranes (MTAMs) comprising one or more layers of fiber assemblies. The electrospun fibers, fiber assemblies, and MTAMs have a high specific surface area ratio and can therefore be used in a variety of applications, such as drug screening, matrix-based cell culture, fermentation, tissue engineering, drug screening (e.g., cancer drug screening and drug screening for cancer immunotherapy), and filtration (e.g., dialysis).

[0029] Hollow electrospun fiber assemblies with fibers having nanoscale hair-like structures The hollow electrospun fiber assemblies and MTAM fibers have hair-like structures extending from the inner surface of the fibers. The hair-like structures extend from the inner surface of the fibers. The surface coverage of the hair-like structures is about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, about 40% to about 80%, about 40% to about 70%, about 50% to about 80%, or about 60% to about 80%. The surface coverage can be estimated based on SEM images. The hair-like structure in the fiber provides a larger surface area and is easily scalable, thereby requiring fewer fibers for use in various applications, thus reducing costs. Additionally, the "hairs" may have an aspect ratio of up to 20:1. Embodiments of aspect ratios of the hair-like structure include, but are not limited to, up to 15:1, up to 10:1, at least 1:1, at least 3:1, or at least 5:1, and from 1:1 to 20:1.

[0030] The fibers are hollow and have pores on the inner surface. In one embodiment, the fibers are hollow and have pores on both the inner and outer surfaces. The pores on the surface of the fibers give the fiber assembly a "sponge-like" appearance. In certain embodiments, the thickness of the fibers ranges from 1 to 5 μm, such as 1.5 to 4 μm, 2 to 3 μm, etc.

[0031] In the electrospinning process, the formation of electrospun fibers can be divided into three stages: (1) Taylor cone, (2) stable jet, and (3) unstable jet (Polym Int 56:1361-1366, 2007). Coaxial electrospinning can also be used to electrospin a first polymer solution as a sheath around a second polymer solution as a core. Through this process, the polymer solutions are delivered through a coaxial spinneret. Fibers can be produced using the method disclosed in US20150342719A1, the entirety of which is incorporated by reference.

[0032] The present invention also provides a method for preparing fibers having nanoscale hair-like structures, comprising using in a two-fluid coaxial electrospinning process a polymeric core solution comprising about 5 wt % to about 40 wt % polymer solution dissolved in a solvent at a ratio of about 7:about 2 to about 9:about 1, and a polymeric sheath solution comprising about 5 wt % to about 40 wt % polymer solution dissolved in a solvent at a ratio of about 7:about 2 to about 9:about 1. In one embodiment, the solvent is a dichloromethane:dimethylformaldehyde (DCM:DMF) cosolvent.

[0033] Embodiments of polymers used as the core or sheath solutions include ethylene oxide, polyethylene oxide (PEO), ethylene glycol, polyethylene glycol (PEG), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), nylon, polyester, polyamide, poly(amic acid), polyimide, polyether, polyketone, polyurethane, polycaprolactone, polyacrylonitrile, polyaramid, conjugated polymers such as electroluminescent polymers, poly(2-methoxy,5-ethyl ( Polyphenylene vinylenes include, but are not limited to, 2'-hexyloxy)para-phenylene vinylene (MEH-PPV), polyphenylene vinylenes, polyarylene-vinylenes, polythienolene-vinylenes, polypyrrolo-vinylenes, polyheteroarylene-vinylenes, polyanilines, polyphenylenes, polyarylenes, polythiophenes, polypyrroles, polyheteroarylenes, polyphenylene-ethynylenes, polyarylene-ethynylenes, polythieno-ethynylenes, polyheteroarylene-ethynylenes, and mixtures thereof. In some embodiments, the polymer is a biodegradable and / or bioabsorbable polymer, such as polyglycolide (PGA) and its random copolymer poly(glycolide-co-lactide) (PGA-co-PLA), polyhydroxyalkyl methacrylates including ethyl methacrylate, and hydrogels such as polyvinylpyrrolidone, polyacrylamide, collagen, gelatin, alginate, chitin, chitosan, fibrin, hyaluronic acid, dextran, and polyamino acids, or mixtures thereof. In further embodiments, the solution is a mixture of PLA, PEO, and PEG.

[0034] In a further embodiment, a flow rate of 3 to 10 mL (core solution) and 2 to 12 mL (sheath solution) and / or a drum collector collection speed of about 80 to about 120 rpm was used in the method of the present invention.

[0035] Microtube array membranes having one or more layers of fiber assemblies In another aspect, the present invention provides a microtube array membrane (MTAM) comprising one or more fiber assemblies described herein.

[0036] In one embodiment, the MTAM has a structure in which layers of fiber assemblies are arranged alternately, referred to as alternating layers. As used herein, the terms "alternating" or "alternating layers" mean that the fiber layers are closely stacked and not perfectly aligned in the z-direction of the layers. For example, the fiber layers in a two-layer membrane may have an "AB" configuration when viewed through the z-direction. For a three-layer membrane, the fiber layers may have an "ABA" or "ABC" configuration when viewed through the z-direction. As used herein, the terms "vertically" or "vertical layers" mean that the fiber layers are closely stacked and perfectly aligned in the z-direction of the layers. All of these MTMAs are referred to as "MTMA-al," although additional suffixes can be added to clearly identify the MTMA configuration and number of layers. For example, an MTMA with two alternating layers can be referred to as "MTMA-dl-al." Additionally, MTMA-alternating layers may exhibit the following characteristics or benefits: minimized area waste, higher packing density, and the possibility of adding additional tubes, which may reduce system pressure.

[0037] In another embodiment, the MTMA has a structure in which layers of fiber assemblies are arranged vertically, referred to as vertical layers. In other words, the MTMA has multiple layers of fibers aligned in the z-direction (perpendicular to the membrane surface). For example, an MTMA with two layers of fibers aligned in the z-direction is represented by "MTMA-dl," an MTMA with three layers of fibers aligned in the z-direction is represented by "MTMA-tl," and so on. MTMAs with additional layers of fibers may also be provided. MTMA-vertical layers may exhibit the following characteristics or benefits: higher packing density, enhanced mechanical properties, and easy handling due to the continuous framework.

[0038] The present invention also provides a method for preparing MTAM having multiple layers of fibers aligned in the z-direction, comprising using a sheath solution comprising about 15 wt% to about 25 wt% polymer solution in a sheath-fluid coaxial electrospinning process at a flow rate greater than 10 mL / hr and a voltage of about 8 kV to about 11 kV, while maintaining a spinneret height of about 1 to 3 cm. In one embodiment, the polymer solution is PSF / PVP dissolved in a cosolvent of THF and DMAC. The preparation of MTAM-dl-al having a multilayer structure comprises using a sheath solution comprising about 15 wt% to about 25 wt% polymer solution in a sheath-fluid coaxial electrospinning process at a flow rate greater than 10 mL / hr and a voltage of about 8 kV to about 11 kV. In one embodiment, the polymer solution is PSF / PVP dissolved in a cosolvent of THF and DMAC.

[0039] These types of MTAMs have a large surface-to-volume ratio and can be targeted for absorption-based applications, such as endotoxin removal, CTC capture, as a metastasis prevention / diagnostic device, etc. Furthermore, these systems can also be applied in applications in rapid biosensing of diseases.

[0040] The number of MTAM fibers packed together in the fiber assembly and the orientation angle of the fibers represent the degree of packing and alignment, respectively. A larger number of fibers means a higher packing density, whereas a smaller orientation angle indicates the degree of alignment of the electrospun fibers.

[0041] In another aspect, the present invention provides a pocket surrounding any of the microtube array membranes (MTAMs) described above. Techniques for creating a bioavailable pocket can be conventional in the art. Examples of materials for creating the pocket include, but are not limited to, polysulfone, polylactic acid, and most solvent-soluble polymers.

[0042] The pockets surrounding the claimed MTMAs may be useful in medical, pharmaceutical, or biological applications, for example, the pockets may be used for drug screening, endotoxin removal, filtration, separation, etc.

[0043] Without being bound by theory, hairy MTMA-multilayers may exhibit the following characteristics or benefits: greater surface area, enhanced cell attachment via nanotopography that induces adhesion-promoting proteins, greater packing density, etc.

[0044] The examples and embodiments disclosed herein should be construed as merely for purposes of illustration and illustration, and not as limiting the scope of the present invention in any way. It will be apparent to those skilled in the art with the aid of the present invention that variations can be made to the details of the above-described embodiments without departing from the basic principles of the disclosure. It is intended that the scope of the present invention be defined by the claims appended hereto and their equivalents. The following is one embodiment of the present invention. (1) A hollow electrospun fiber assembly comprising a plurality of fibers having nanoscale hair-like structures extending from their inner surfaces. (2) The hollow electrospun fiber assembly according to (1), wherein the hair-like structures have a length in the range of 100 nm to 1 μm. (3) The hollow electrospun fiber assembly according to (1), wherein the hair-like structures have an aspect ratio of up to 20:1. (4) The hollow electrospun fiber assembly according to (1), wherein the surface coverage of the hair-like structures is about 10% to about 80%. (5) The hollow electrospun fiber assembly according to (1), wherein the fibers have pores on the surface with a size ranging from 5 nm to 1 μm. (6) Fibers are made of ethylene oxide, polyethylene oxide (PEO), ethylene glycol, polyethylene glycol (PEG), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), nylon, polyester, polyamide, poly(amino acid), polyimide, polyether, polyketone, polyurethane, polycaprolactone, polyacrylonitrile, polyaramid, conjugated polymer, poly(2-methoxy,5-ethyl(2'-hexyloxy) para-phenylene vinylene) (MEH-PPV), polypropylene, polypropylene copolymer ... The hollow electrospun fiber assembly according to (1), which is composed of a polymer selected from the group consisting of phenylene vinylene, polyarylene vinylene, polythienole vinylene, polypyrrolo vinylene, polyheteroarylene vinylene, polyaniline, polyphenylene, polyarylene, polythiophene, polypyrrole, polyheteroarylene, polyphenylene ethynylene, polyarylene ethynylene, polythieno ethynylene, polyheteroarylene ethynylene, and mixtures thereof. (7) The hollow electrospun fiber assembly according to (1), wherein the fibers have a core-sheath structure and the core is composed of a mixture of PLA, PEO, and PEG. (8) The hollow electrospun fiber assembly according to (1), wherein the ratio of the length to the diameter (outside) of the fiber (L / d) is greater than about 20. (9) A microtube array membrane (MTAM) comprising one or more layers of the hollow electrospun fiber assembly described in (1). (10) The MTAM according to (9), comprising at least two layers of a fiber assembly. (11) The MTAM according to (9), having a structure in which fiber layers are arranged alternately or perpendicularly. (12) A pocket surrounding the MTMA described in (1). (13) A pocket surrounding the MTMA described in (9). (14) A method of using the hollow electrospun fiber assembly according to (1) in drug screening, matrix-type cell culture, fermentation, tissue engineering, drug screening, or filtration. (15) A method of using the MTAM according to (9) in drug screening, matrix-type cell culture, fermentation, tissue engineering, drug screening, or filtration. [Example]

[0045] [Example 1] Hairy microtube array membrane (MTMA-hairy) The materials used as the core solution in the fabrication of hollow fiber assemblies were poly-L-lactic acid (PLLA, Mw = 140 KDa, Japan), poly-ethylene glycol (PEG, Mw = 35,000 Da, Sigma-Aldrich), and poly-ethylene oxide (PEO, Mw = 900,000 Da, Sigma-Aldrich), and the solvents dichloromethane (DCM, Mallinckrodt, USA) and N,N-dimethylformamide (DMF) were purchased from Sigma-Aldrich, Inc. (St. Louis, MO).

[0046] The outer sheath solution was a 15% poly(lactic acid) (PLLA) solution in a 9:1 solvent mixture of dichloromethane (DCM) and N,N-dimethylformamide (DMF). The inner core solution was prepared by first dissolving PLLA in an 8:2 DCM:DMF solvent mixture to form a 15 wt% PLLA solution, then adding 1.3 g of polyethylene oxide (PEO) and 1.3 g of polyethylene glycol (PEG) to the PLLA solution. Upon complete dissolution, 20 mL of acetone was added to the mixture, which was then sonicated for at least 3 hours. The electrospinning parameters for obtaining PLLA / PLLA-PEG-PEO sheath-core fibers were as follows: applied voltage of 7.2 kV with a maximum amperage of 200 μA, inner flow rate of 5 mL / h, outer flow rate of 6 mL / h, and drum collector collection speed of 100 rpm.

[0047] Figure 1 shows SEM images of the thus obtained MTMA-h at various magnifications.

[0048] [Example 2] Hairy microtube array membrane (MTMA-hairy) The fabrication parameters were similar to those outlined in Example 1. The core solution formulation consisted of 5 wt% PLLA dissolved in a solvent mixture of DCM:DMF in an 8:2 ratio. Once completely dissolved, 1 mL of polyethylene glycol (PEG40, M wPEG40 (40KD, which acts as a surfactant) was added to the mixture and stirred for 3 hours. The sheath solution consisted of 15 wt% PLLA dissolved in a co-solvent of DCM:DMF in an 8:2 ratio until homogeneous.

[0049] Figure 2 shows SEM images of the thus obtained MTMA-p at various magnifications. An ultrafine, ultraporous, sponge-like structure is clearly visible on the inner surface of the MTAM-hairs.

[0050] [Example 3] Multilayer microtube array membrane The parameters for electrospun MTMA were varied. The sheath solution contained 20 wt% polysulfone / polyvinylpyrrolidone (PSF / PVP) in a THF / DMAC solvent mixture under high flow rate conditions (>10 mL / hr) and voltages of 8 kV to 11 kV. The collector was set at a rotation speed of 50 to 60 rpm. Figure 3 shows SEM images of an MTMA with two layers, i.e., MTMA-dl (Figure 3(a) cross-sectional view, Figure 3(b) top view). Figure 4 shows SEM images of an MTMA with two alternating layers, i.e., MTMA-dl-al (Figure 4(a) cross-sectional view, Figure 4(b) top view). Figure 5 demonstrates the reproducibility of MTMA-dl-al prepared in various batches by the same or different fabricators.

[0051] [Example 4] Multilayer microtube array membrane with hair-like structure We prepared MTAM with an alternating layer structure by varying the parameters for electrospun MTAM. Under high flow rate conditions (>10 mL / hr) and voltages of 8 kV to 11 kV, the sheath solution contained 20 wt% polysulfone / polyvinylpyrrolidone (PSF / PVP) in a THF / DMAC solvent mixture. The collector was set at a rotation speed of 50 to 60 rpm. Figure 6 shows an SEM image of an MTMA with two layers of hair-like structures on the surface of the microtube wall, i.e., MTMA-dl-h.

[0052] [Example 5] Cell viability test In tissue engineering, one key factor that defines cell attachment is the presence of nanotopography, which contributes to initial protein adsorption and subsequent cell attachment. When using the MTMAs of the present invention in anticancer drug screening applications, a major challenge is ensuring significant differences between the control group and the group administered the desired anticancer drug. Therefore, it is crucial that initial tumorigenicity be enhanced. This can be achieved by utilizing MTAM-h or other MTMAs provided herein, as they provide the nanotopography that is crucial for cancer cell attachment and proliferation.

[0053] In this example, the lung cancer cell line A549 was used as a model. The cells were cultured in RPMI 1640 medium for 24 hours. Then, 1 x 10 cells in a 10 μL droplet were cultured. 4 The cells were transferred to a sheet of sterile parafilm and siphoned into the lumen of MTAM (without surface nanotopography) and the MTAM-h of the present invention. The lumen of these MTAMs was sealed by folding over the ends, and they were cultured at 37°C in RPMI 1640 medium under a 5% carbon dioxide atmosphere. Samples were collected on days 1, 4, and 7, and an MTT assay was performed to determine cell viability. The results are shown in Figure 7.

[0054] Statistical analysis revealed a significant difference (p<0.005) between the cell viability of A549 cells cultured on MTAM without surface nanotopography and the MTAM-h of the present invention, strongly suggesting that the nanotopography present in MTAM-h plays an important role in overall increasing the cell viability of A549 cells.

[0055] [Example 6] Endotoxin removal test In this example, MTAM-h is used in endotoxin removal applications. Experiments were conducted to evaluate the absorption capacity of MTAM-h of the present invention and MTAM without nanotopography.

[0056] The procedure involved acetic acid plasma treatment of the PLLA-MTAM surface, both MTAM and MTAM-h. This treatment significantly reduced the water contact angle, indicating increased hydrophilicity. Furthermore, acetic acid plasma treatment allows more hydroxyl termini to be present on the PLLA-MTAM surface, thereby allowing for greater immobilization (via UV light) of polymyxin B, an antibiotic commonly used in commercial endotoxin removal products, such as Toraymyxin. Both types of MTAM were then transferred to two different solutions containing endotoxin at a concentration of 100 EU / mL. After 60 minutes, the surrounding solutions were separately collected and tested to assess endotoxin levels.

[0057] The results showed that compared with MTAM without surface nanotopography, MTAM-h exhibited a significantly higher absorption capacity by approximately 13% (see FIG. 8). Furthermore, statistical analysis revealed that such a difference was significant. Without being bound by theory, nanotopography / nanostructures such as hair-like structures significantly increase the overall available surface area due to the increased surface area, thereby providing more sites for polymyxin B adsorption. This result explains the higher absorption capacity of endotoxin levels.

[0058] Another example is provided to illustrate the use of MTAM-al in endotoxin removal applications. Experiments were conducted to evaluate the absorption capacity of MTAM-al of the present invention and Toraymyxin™, a conventional product for endotoxin removal.

[0059] The results showed that compared to Toraymyxin™, MTAM-al exhibited comparable, and even significantly higher, absorption capacities. Furthermore, statistical analysis revealed that such differences were significant. Without being bound by theory, the claimed MTAM-al possesses a larger surface area than monolayer MTAM (e.g., in one example, a 1.3-fold increase), thereby providing more sites for adsorption of polymyxin B. The unique structure of the claimed MTAM-al also allows for a higher absorption capacity than can be provided by the conventional material, Toraymyxin™ (see Figure 9).

Claims

1. A hollow electrospun fiber assembly comprising a plurality of hollow electrospun fibers having nanoscale hair-like structures extending from the inner surface of the fibers.

2. 2. The hollow electrospun fiber assembly of claim 1, wherein the hair-like structures have a length in the range of 100 nm to 1 μm.

3. 2. The hollow electrospun fiber assembly of claim 1, wherein the hair-like structures have an aspect (L / d) ratio of up to 20:

1.

4. 2. The hollow electrospun fiber assembly of claim 1, wherein the fibers have pores on the surface having a size ranging from 5 nm to 1 μm.

5. Fibers may be made of ethylene oxide, polyethylene oxide (PEO), ethylene glycol, polyethylene glycol (PEG), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), nylon, polyester, polyamide, poly(amino acid), polyimide, polyether, polyketone, polyurethane, polycaprolactone, polyacrylonitrile, polyaramid, conjugated polymer, poly(2-methoxy,5-ethyl(2'-hexyloxy) para-phenylene vinylene) (MEH-PPV), polyphenylene 2. The hollow electrospun fiber assembly of claim 1, wherein the hollow electrospun fiber assembly is composed of a polymer selected from the group consisting of olefin vinylenes, polyarylene vinylenes, polythienole vinylenes, polypyrrolo vinylenes, polyheteroarylene vinylenes, polyanilines, polyphenylenes, polyarylenes, polythiophenes, polypyrroles, polyheteroarylenes, polyphenylene ethynylenes, polyarylene ethynylenes, polythieno ethynylenes, polyheteroarylene ethynylenes, and mixtures thereof.

6. 10. The hollow electrospun fiber assembly of claim 1, wherein the fibers have a core-sheath structure, and the core is composed of a mixture of PLA, PEO, and PEG.

7. 2. The hollow electrospun fiber assembly of claim 1, wherein the fiber length to diameter (outer) ratio (L / d) is greater than 20.

8. A microtube array membrane (MTAM) comprising one or more layers of the hollow electrospun fiber assembly of claim 1.

9. 9. The MTAM of claim 8, comprising at least two layers of a fiber assembly.

10. 9. The MTAM of claim 8, having a structure in which layers of fibers are arranged alternately or perpendicularly.

11. 10. A method of using the hollow electrospun fiber assembly of claim 1 in drug screening, matrix-type cell culture, fermentation, tissue engineering, drug screening, or filtration.

12. 10. A method of using the MTAM of claim 8 in drug screening, matrix-based cell culture, fermentation, tissue engineering, drug screening, or filtration.

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