201137195 六、發明說明： 【發明所屬之技術領域】 本發明係、關於-種電紡絲纖維組及—種用於製備該纖維 組之靜電輔助纖維紡絲方法。特定言之，本發明提供一種 超问順向與緊岔排列之纖維組（其中至少5個纖維緊密排列 在一起，且纖維之定向不大於+/_5。）及其製備與應用。 【先前技術】 需要促進組織浸潤以修復/再生罹病或受損組織之生物 醫學材料（較佳地，生物可相容及生物可降解之結構基質） 。組織工程涉及開發能夠與生物組織進行特定相互作用以 得到功能組織等效物之新一代生物材料。歸因於製造方法 之極端條件（諸如，高溫或低溫），大多數架構僅可在架構 完成之後導入細胞及/或信號。在架構之内部部分中接種 細胞可能有難度，尤其係對於具有精細結構特徵之較大物 件而言。若細胞可另以原位的方式導入至架構中的話，其 Q 係會非常有益的。此外，化學喪入物（chemical cue)(諸如 ，生長因子）之添加，係可藉由微調生物可降解聚合物（諸 如，膠原蛋白、聚乳酸及PCL)之降解機制以受控方式來達 成。 吾人已知，具有芯鞘、中空或多孔結構之奈米管及奈米 纖維在各種各樣的技術（包括（例如）生物醫學材料、架構及 組織再生及過遽）中具有許多有前景的應用。此等纖維在 線性、一維及二維結構中展現重量輕、具可撓性、耳可、灸 透性、堅固及具彈性之性質的特別有利的組合。就生物醫 145321.doc 201137195 學應用而言，存在對設計模擬組織以用於較佳組織再生之 力木構㈣的極大興趣。超高順向結構最佳的代表，為神經 、血官及一些其他組織或其部分之結構。 電紡絲為藉由電荷以使自喷嘴尖口所噴出之聚合溶液錐 形小液滴變形為超精細纖維的製程。電紡絲使對來自許多 不同材料(包括(但不限於)聚合物)之連續奈米纖維進行紡 絲變得相對容易。電纺絲提供直接且實用的方式來製造直 仏在成不米至約兩千奈米之範圍内的纖維。電紡絲為用於 製造呈膜或3-D結構形式之微求至奈米級纖維之多用途的 低成本方法。2007年的P〇lym int 56:1361 —1366中介紹了用 於製備電紡絲奈米纖維之裝置。w〇 2〇〇5〇95684係關於具 有芯殼型結構（core_and_shell structure)之實質上連續纖維 ，然而，此等纖維係無規配置、非順向且緊密排列的。當 前’僅有一些關於超高順向電紡絲纖維製造之報告，其係 藉由使用以下各項來收集纖維而達成：旋轉圓盤（A.201137195 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to an electrospun fiber group and a method for producing an electrostatically assisted fiber for producing the fiber group. In particular, the present invention provides a fiber group in which the forward and next arrays are interrogated (at least 5 of which are closely packed together and the orientation of the fibers is no greater than +/_5) and their preparation and application. [Prior Art] There is a need for biomedical materials (preferably, biocompatible and biodegradable structural matrices) that promote tissue infiltration to repair/regenerate rickets or damaged tissues. 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. The Q system can be very beneficial if the cells can be introduced into the architecture in an in situ manner. In addition, 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 over-twisting. . These fibers exhibit a particularly advantageous combination of light weight, flexibility, ear, moxibustion, firmness and elasticity in linear, one-dimensional and two-dimensional structures. As far as biomedical applications are concerned, there is great interest in designing simulated structures for better tissue regeneration (4). The best representation of ultra-high directional structures is the structure of nerves, blood organs, 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 in the range of up to about two thousand nanometers. Electrospinning is a low cost method for the versatility of micro-finished nanofibers in the form of films or 3-D structures. A device for preparing electrospun nanofibers is described in P.lym int 56: 1361 - 1366, 2007. W〇 2〇〇5〇95684 is a substantially continuous fiber having a core_and_shell structure, however, these fibers are randomly arranged, non-directional and closely aligned. There are only a few reports on the manufacture of ultra-high-parallel electrospun fibers, which are achieved by collecting fibers using the following: Rotating discs (A.
Theron、E. Zussmanl 及 A. L. Yarin 之 2001 年的「Theron, E. Zussmanl and A. L. Yarin's 2001
Electrostatic field-assisted alignment of electrospun nanofibres」（Nanotechnology，第 12 卷第 384 至 390 頁））、轉 鼓（P. Katta、Μ· Alessandro、R. D. Ramsier 及 G· G. Chase 之 2004 年的「Continuous Electrospinning of Aligned Polymer Nanofibers onto a Wire Drum Collector」(Nano Lett，第 4卷第 11 號）），或框架（H. Fong、W-D. Liu、C-S. Wang、RA.Vaia 之 2002 年的「Generation of electrospun fibers of nylon 6 and nylon 6-montmoril Ionite 145321.doc 201137195 nanocomposite」（Polymer’ 43(3)’ 第 775 至780 頁））；或該 製造係藉由使用如下一項來收集纖維而達成：一組平行導 電基板（Dan Li、Yuliang Wang 及 Younan Xia 之 2003 年的「 Electrospinning of Polymeric and Ceramic Nanofibers as Uniaxially Aligned Arrays」（Nano Lett.，第 3卷第 8號））。 藉助於多領域技術的某種程度之纖維定向（J.M. Deitzel、J. Kleinmeyer、J.K· Hirvonen、Beck TNC.之 2001 年的「 Controlled deposition of electrospun poly(ethylene oxide) fibers」（Polymer，第42卷第8 163至8 170頁））亦已有報告。 此外，US 7,575,707揭示了 一種用於對具有芯鞘、管狀或 複合結構之奈米纖維進行電紡絲之方法。 然而，上述參照案皆具有有限順向之缺點，其甚至會隨 著經沈積纖維層生長得愈來愈厚而變得愈來愈糟。以織針 型紡絲頭進行電紡絲之極有限的製造速度及/或小製造量 亦係令人煩惱的，此使其缺乏工業價值。 藉由電紡絲製程來製備奈米/微米管之報告為少數。Li 等人已報告藉由單一毛細管電紡絲製備奈米管（Li，X.H.S·， Chang L.及 Liu，Yi C.之 2007 年的 A. Simple Method for Controllable Preparation of p〇iymer Nanotubes via a Single Capillary Electrospinning. Langmuir(23 ：第 10920至 10923 頁））。Srivastava亦已使用流體動力流體，聚焦於微通道設 計來製備芯/鞘、PPy/PVP及中空PVP奈米纖維（Y. Srivastava，C. Rhodes, M. Marquez, T. Thorsen之 2005年的 Electrospinning hollow and core/sheath nanofibers using 145321.doc 201137195 hydrodynamic fluid focusing » Microfluid Nanofluid > 5 * 第455至458頁）。Di等人已藉由將自對聚（乙烯吡咯n定綱 )(P VP)/乙醇溶液中之矽質岩類_ i奈米粒子進行同軸電紡絲 所得之初纺纖維锻燒成外殼且使石壞油充當内部液體來掣 備彿石中空纖維（J. Di，H. Chen, X. Wang，Y· Zhao, L Jiang，J· Yu，R.以之2〇〇8年的以心化如⑽〇f Ze〇lite Hollow Fibers by Coaxial Electrospinning。Chem Mater， 2〇(Π)··第3543至3545頁）。然而，其皆不能夠製備超高顺 向與超高緊密排列之微管。因此，需要開發結構順向與緊 密排列之纖維。 ' 【發明内容】 本發明之—目標係提供-種超高順向與緊密排列之纖維 組’其中至少五(5)個纖維緊密排列在一起以形成單一層， 且纖維之定向不大於+/_ 5。。 二==目標係提供一種藉由對聚合溶液進行電紡 猶備本發明之纖維組的方法，其包含：藉由調整電纺 來增：經嗔射纖維之重量，使得在溶液中之溶劑 %每二IT纖維之重量為其原始重量的最少4〇%。 【只施方式】 本發明允許開私— 可用於醫渗哭杜/ ⑸順向與緊密排列之纖維組，其 件（諸如’用於組織再生之架構及膜）及微管 儘管本文中所使 療及科學背景内使 用之許多詞語 用且能理解， 、術S吾及標題常在傳統醫 但下文中係提供一些術語 145321.doc 201137195 ’以及特定名稱、命名、種名或稱號之 此等描述及定義係提供以幫助辨識及瞭 明之方法之範疇内之應用的真實種類及 ± ^ pa T D〇兒紡絲」指使用流體動力學盥 唧電表面之間的相互作 被稱作電紡絲纖維)的技術 纖維€ 〇 成涉及將溶液提供至盘 “ § ’ Μ絲纖維之形 甘士& ，、電愿源進行電通信之主體中的孔口 ’其中電力輔助形成精細纖維 中的孔口 方式處於比/、沈積於可接地或以其他 / 主體之電壓低之電壓的表面上。在電… 將自-或多個織針、狹槽 名 、、方4中’ Μ充電至相對於收集拇所:溶液或 ，且導致聚合溶液或炫體之精 =克服表面張力 相反電荷之收集柵格。 n-移動朝向接地或帶 如本文中所使用，術語「 〇 之概要描述及定義 概要描述及定義。 解意欲包括於本發 範圍。 限於）均聚物、並物」扣且通常包括（但不 聚物、三元共聚、接枝、無規及交替共 ，其可包括（但不限於）聚=與變體。較佳地 烯腈、聚胺基甲酸、平山 聚礼酉欠、聚烯烴、聚丙 •夂S日 t碳酸酷、取j (PVA)、纖维f、％ ♦己内酯、聚乙烯醇 、耐綸6-6，笪楚、 、（例如，耐綸ό、耐綸400 寻寻）、聚苯乙 其組合。除# ^ + 蛋白質，及其類似物，或 括材料之所有可能的幾何、組離否^語「聚合物」意欲包 等規、間規及無規對稱性。態包括(但不㈣ 、各來合物之溶劑可選自為 145321.doc 201137195 熟習此項技術者所知之溶劑，包括（但不限於）硫酸、甲酸 、氯仿、四氫呋喃、二曱基甲醯胺、水、丙酮，及其組合 〇 如本文中所使用，術語「奈米大小之纖維」或「奈米纖 維」指代平均直徑不大於約1500奈米（nm)的極小直徑之纖 維。奈米纖維通常被理解成其纖維直徑範圍為約10 11111至 約1500 nm ’更具體言之為約1〇 ηηι至約1000 nm，又更具 體δ之為約20 nm至約5〇〇 nm，且最具體言之為約2〇 ^^至 約400 nm。其他例示性範圍包括約5〇 nm至約5〇〇 nm、約 100 nm至500 nm，或約4〇 nm至約2〇〇 nm。在存在微粒且 其非均勻地分佈於奈米纖維上的情況下，可使用已知技術 (例如，與電子顯微法輕合之影像分析^具）來量測奈米纖 .准之平均直1但排除因存在額外粒子而相對於纖維之無 粒子部分實質上增大的纖雉之部分。 … 如本文中所使用，術語「定向纖維」指特定結構或陣列 中之實質上所有、纖#皆經配置成在縱向方向上彼此平行（ 「早向定向」）或在定義明確之三維網路中彼此平行（「三 維定向」）。換言《，㈣纖維相對於彼此在^間上並 無規地配置。在大多翁棒、·^ , 、 障况下，本文中所描述之纖維 對於支樓基板表面之大體上齿吉古a u a e 體上垂直方向上生長，且存在個別 纖維絲束之最小（若有的話）分支。 〜 如本文中所使用，術往「 从刺β 「 了°。早—材枓層」或「單層材粗 指代由厚度可變化之單—層構成的材料。 科」 如本文中所使用，術語「複數個層」或「多層材料 •J子曰 145321.doc 201137195 代單層材料之「堆疊」。 超高順向與緊密排列之纖維紐 雜fn中’本發明提供—種超高順向與緊密排列之纖 、.’、”且’其中至少五⑺個纖維緊密排列在一起 ’且纖維之宏Α π +认本/ <〇 早 增 扣、 疋向不大於+/_5 。根據本發明，纖維可為中 空或實心的。較佳地，纖維為中空的。Electrostatic field-assisted alignment of electrospun nanofibres" (Nanotechnology, Vol. 12, pp. 384-390)), Drums (P. Katta, Μ·Alessandro, RD Ramsier, and G. G. 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-montmoril Ionite 145321.doc 201137195 nanocomposite" (Polymer' 43(3) 'pp. 775-780); or the fabrication is achieved by using the following to collect fibers: a set of parallel conductive Substrate (Dan Li, Yuliang Wang, and Younan Xia, 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 8 163 to 8 170 pages)) has also been reported. Further, US 7,575,707 discloses a method for electrospinning nanofibers having a core sheath, tubular or composite structure. However, the above references all have the disadvantage of limited directionality, which may even get 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 p〇iymer Nanotubes via a Single Capillary Electrospinning. Langmuir (23: p. 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 145321.doc 201137195 hydrodynamic fluid focusing » Microfluid Nanofluid > 5 * Pages 455-458). Di et al. have forged and fired the as-spun fibers obtained by coaxial electrospinning of silicate-type nanoparticles from p-poly(vinylpyrrole n-design) (P VP)/ethanol solution. Stone bad oil acts as an internal liquid to prepare Foshan hollow fiber (J. Di, H. Chen, X. Wang, Y· Zhao, L Jiang, J. Yu, R. For example, (10) 〇f Ze〇lite Hollow Fibers by Coaxial Electrospinning. Chem Mater, 2〇(Π)··pages 3543 to 3545). However, none of them is capable of producing ultra-high-order and ultra-highly closely packed microtubes. Therefore, it is necessary to develop fibers that are structurally aligned and closely aligned. SUMMARY OF THE INVENTION The object of the present invention is to provide an ultra-high-order and closely-aligned fiber group in which at least five (5) fibers are closely arranged together to form a single layer, and the orientation of the fibers is not greater than +/ _ 5. . The second == target system provides a method for electrospinning a polymerization solution according to the present invention, which comprises: increasing by electrospinning: the weight of the entangled fiber, so that the solvent in the solution is % The weight of each of the two IT fibers is at least 4% of the original weight. [Applicable only] The present invention allows for the opening of the smear - can be used for medicinal diarrhea / (5) compliant and closely aligned groups of fibers, such as 'architectures and membranes for tissue regeneration" and microtubules, although Many of the words used in the context of therapy and science are understood and understood, and the terms are often used in traditional medicine but are provided below with some terms 145321.doc 201137195 'and descriptions of specific names, naming, species names or titles And definitions are provided to help identify and identify the true type of application within the scope of the method and ± ^ 〇 纺 纺 」 」 指 指 指 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用 使用The technical fiber 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及 涉及The mode is on the surface of / or, deposited on a voltage that can be grounded or at a voltage lower than the voltage of the other / body. In the electric ... will be charged from - or a plurality of knitting needles, slot name, square 4 'to the collection thumb : solution or, and resulting in a polymerization solution or brilliance = a collection grid that overcomes the opposite charge of surface tension. n-moving towards ground or belt as used herein, the term "summary" describes and defines a summary description and definition. The intention is to be included in the scope of the present invention. Limited to homopolymers, conjugates and usually include (but not polymer, terpolymer, graft, random and alternating, which may include, but is not limited to, poly = And variants. Preferably, the nitrile, the polyaminocarbamic acid, the Pingshan, the polyolefin, the polypropylene, the polystyrene, the j (PVA), the fiber f, the % ♦ caprolactone, the poly Vinyl alcohol, nylon 6-6, 笪 、, (for example, nylon ό, nylon 400 search), polystyrene and its combination. Except # ^ + protein, its analogues, or all possible materials Geometry, group departure or not "polymer" is intended to include isotactic, syndiotactic and random symmetry. The state includes (but not (d), the solvent of each compound can be selected from 145321.doc 201137195 familiar with this technology Solvents known, including but not limited to sulfuric acid, formic acid, chloroform, tetrahydrofuran Dimercaptocarbamide, water, acetone, and combinations thereof As used herein, the term "nano-sized fibers" or "nanofibers" refers to a minimum of an average diameter of no greater than about 1500 nanometers (nm). Diameter fibers. Nanofibers are generally understood to have fiber diameters ranging from about 10 11111 to about 1500 nm 'more specifically from about 1 〇ηηι to about 1000 nm, and more specifically δ from about 20 nm to about 5 〇〇 nm, and most specifically about 2 〇 ^ ^ to about 400 nm. Other exemplary ranges include from about 5 〇 nm to about 5 〇〇 nm, from about 100 nm to 500 nm, or from about 4 〇 nm to about 2〇〇nm. In the presence of microparticles which are non-uniformly distributed on the nanofibers, known techniques (eg, image analysis coupled with electron microscopy) can be used to measure the nanofibers. 1 However, the portion of the fiber which is substantially increased relative to the particle-free portion of the fiber due to the presence of additional particles is excluded. As used herein, the term "oriented fiber" refers to substantially all of the structures or arrays that are configured to be parallel to each other in the longitudinal direction ("early orientation") or in a well-defined three-dimensional network. Parallel to each other ("3D orientation"). In other words, (4) the fibers are randomly arranged relative to each other. In most cases, the fibers described in this paper are grown vertically in the direction of the general tooth-gau auae body on the surface of the support substrate, and there is a minimum of individual fiber tows (if any). Branch). ~ As used in this article, the technique is as follows: "From the thorn β "° °. Early - 枓 layer" or "Single layer coarse refers to a material composed of a single layer of varying thickness." , the term "multiple layers" or "multilayer materials." J 曰 145321.doc 201137195 generation of single layer material "stacking". In the ultra-high-order and closely-aligned fibers, the invention provides a super-high-order and closely-aligned fiber, .', and 'of which at least five (7) fibers are closely arranged together' and the fiber macro Α π + recognition / < early expansion, 疋 direction is not greater than + / _ 5. According to the invention, the fibers may be hollow or solid. Preferably, the fibers are hollow.
Y Hi中緊讀列在—起之纖维的數目及纖維的定向角 分別表示緊密排列程度及順向程度。較大纖維數目意謂較 大緊：：列密度’而較小定向角展示電紡絲纖維順向程度 一在⑯例巾，纖維組巾之至少五（5)個纖維緊密排列在 -起；較佳地，至少20個纖維緊密排列在一起；更佳地， 至少50個纖維緊密排列在-起；且最佳地，至少100個或 200」固纖維緊密排列在一起。在另外實施例中，纖維組中 緊密排列在-起之纖維的數目係在5至200、10至200、2〇 至2〇〇、20至100、5〇至2〇〇或5〇至1〇〇之範圍内。 在另一實施例中’纖維組中之纖維定向不大於+/- 5。； 較佳地，不大於仏4。；更佳地，不大於+/_ &最佳地， '丨1在一另外貫施例中，纖維組中之纖維定向 為約。至約+/-5。，且更佳地，為約+H。至約+/_4〇。 纖、隹之長度對直徑(外裎)比(L/句為纖維之緊密排列密度 的另參數。根據本發明之另一實施例，L/d大於約。 軏佺地L/d大於約100 ’更佳地，大於約丨，，且最佳地 大於約1〇,〇〇〇。在本發明之一實施例中，為約至约 1〇,〇〇〇°較佳地，該比為約2〇至1，000,且更佳地，為約20 145321.doc 201137195 至約100。 根據本發明所製備之纖維組中之纖維為中空的。纖維直 徑不為本發明之本質特性。纖維組中之纖維的平均内徑為 約1 μιη(微米）至約1 00 μιη(微米）。更佳地，平均直徑為約 1 0 μm至約5 0 μιη或約1 5 μm至約25 μm。最佳地，平均直 徑為約20 +/- 2 μηι。纖維之平均壁厚度為約0·1 μιη至約10 μ m。更佳地，平均壁厚度為約1 μ m至約5 μ m。最佳地， 平均壁厚度為約3 μιη。 根據本發明，任何合適聚合物可用於製備本發明之纖維 。聚合物之實例包括（但不限於）：環氧乙烷；聚氧化乙烯 (ΡΕΟ)；乙二醇；聚乙二醇（PEG);聚（乳酸）（PLA);聚（乙 醇酸）（PGA);聚（氡化乙稀）（PEO);耐綸；聚酯；聚醯胺 ;聚（醯胺酸）；聚醯亞胺；聚醚；聚酮；聚胺基甲酸酯； 聚己内酯；聚丙烯腈；芳族聚醯胺；共軛聚合物，諸如， 電致發光聚合物；聚（2-甲氧基，5乙基（2’己氧基）對伸苯基 伸乙烯基）(MEH-PPV);聚苯乙烯基；聚伸芳基-伸乙烯基 ;聚伸噻吩幷基-伸乙烯基；聚°比咯幷-伸乙烯基；聚伸雜 芳基-伸乙烯基；聚苯胺；聚苯；聚伸芳基；聚噻吩；聚 吼咯；聚伸雜芳基；聚苯-伸乙炔基；聚伸芳基-伸乙炔基 ;聚噻吩幷-伸乙炔基；聚伸雜芳基-伸乙炔基；及其混合 物。 在可用於製備在醫療應用具有效用之中空纖維的本發明 之一實施例中，聚合物為生物可降解及/或生物可吸收聚 合物，其含有選自由乙交酯、丙交酯、二氧環己酮、己内 145321.doc -10- 201137195 酯及碳酸二亞甲酯組成之群組的單體。短語「含有單體」 意欲指代自指定單體製造或含有指定單體單元之聚合物。 聚合物可為均聚物、無規或嵌段共聚物，或含有此等單體 之任何組合的雜聚合物。材料可為無規共聚物、嵌段共聚 物或3有此等單體之均聚物、共聚物及/或雜聚合物的 摻合物。The number of fibers listed in Y Hi and the orientation angle of the fibers in Y Hi indicate the degree of tight alignment and the degree of forward direction, respectively. The larger number of fibers means a larger tightness: the column density' and the smaller orientation angle shows the degree of directionality of the electrospun fiber in one case of 16 cases, and at least five (5) fibers of the fiber group are closely arranged in the same; Preferably, at least 20 fibers are closely packed together; more preferably, at least 50 fibers are closely packed together; and optimally, at least 100 or 200" solid fibers are closely packed together. In further embodiments, the number of fibers closely aligned in the fiber group is between 5 and 200, 10 to 200, 2 to 2, 20 to 100, 5 to 2 or 5 to 1 Within the scope of 〇〇. In another embodiment, the fiber orientation in the fiber set is no greater than +/- 5. Preferably, it is not larger than 仏4. More preferably, no more than +/_ & optimally, '丨1 In a further embodiment, the fibers in the fiber group are oriented about. Up to about +/-5. And, more preferably, about +H. Up to about +/_4〇. Length to diameter (outer 裎) ratio of fiber and 隹 (L/sentence is another parameter of tightly packed density of fibers. According to another embodiment of the invention, L/d is greater than about. 軏佺L/d is greater than about 100 'More preferably, greater than about 丨, and most preferably greater than about 1 Torr, 〇〇〇. In one embodiment of the invention, from about 1 to about 〇, preferably, the ratio is From about 2 〇 to 1,000, and more preferably from about 20 145321.doc 201137195 to about 100. The fibers in the fiber group prepared according to the present invention are hollow. The fiber diameter is not an essential property of the present invention. The fibers in the set have an average inner diameter of from about 1 μm to about 100 μm, more preferably 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 μηι. 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 μη. Any suitable polymer can be used to prepare 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 (ΡΕΟ); ethylene glycol; polyethylene glycol (PEG); poly (lactic acid) (PLA); poly (glycolic acid) (PGA); poly (deuterated ethylene) (PEO); nylon; polyester; polyamine; poly(proline); polyimine; polyether; polyketone; polyurethane; polycaprolactone; polyacrylonitrile; Polyamine; conjugated polymer, such as electroluminescent polymer; poly(2-methoxy, 5-ethyl(2'hexyloxy)-p-phenylene vinyl) (MEH-PPV); polyphenylene Vinyl; poly(aryl)-extended vinyl; polythiophene-vinyl-extension; polypyrrole-extended vinyl; poly(extended heteroaryl)-polyvinyl; polyaniline; polyphenylene; Aryl; polythiophene; polypyrrole; polyheteroaryl; polyphenyl-exetylene; poly(aryl)-exetylene; polythiophene-exetylene; polyhexamethylene-exetylene; 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 selected from the group consisting of glycolide, propylene Ester, two a monomer consisting of a group consisting of cyclohexanone, 145321.doc -10- 201137195 ester and diammonium carbonate. The phrase "containing monomer" is intended to mean a monomer or a specified monomer unit. The polymer may be a homopolymer, a random or block copolymer, or a heteropolymer containing any combination of such monomers. The material may be a random copolymer, a block copolymer or the like. Blends of homopolymers, copolymers and/or heteropolymers of monomers.
在-實施财，生物可降解及/或生物可吸收聚合物含 有生物可吸收及生物可降解直鏈脂族聚酯，諸如，聚乙交 酯（PGA)及其無規共聚物聚（乙交酯-共-丙交酯）（？(}八_共_ PLA)。食品與藥物管理局（F(K)d — Drug 已核准將此等聚合物用於外科應用（包括用於組織構築之 醫療縫合及架構)。此等合成可吸收材料之優點為其藉由 在含水環境（諸如，體液）中醋主鏈之簡單水解的可降解性 降解產物最終代谢成二氧化碳及水，或可經由腎臟排泄 。此等聚合物極不同於纖維素基材料，纖維素基材料不能 由人體吸收。 合適生物相容性聚合物之其他實例為聚甲基丙烯酸羥烷 基酯(包括甲基丙烯酸乙酯），及水凝膠(諸如，聚乙烯吡咯 疋酮$丙稀醯胺’等等）。其他合適生物可吸收材料為 生物：合物’纟包括膠原蛋白、明膠、褐藻酸、曱殼素、 聚葡萄胺糖、纖維蛋白、玻尿酸、聚葡萄糖及聚胺基酸。 根據本發明，預期使用上述實例之任何組合、共聚物、聚 合物或其摻合物。可藉由已知方法來製備此等生物可吸收 材料。 145321.doc 201137195 特別可用之生物可降解聚合物包括聚-丙交酯、聚-乙交 西曰 ι己内、聚一13惡烧，及其無規及嵌段共聚物。特定 聚合物之實例包括聚d,l-丙交脂及聚丙交酯-共-乙交酯。 在另一實施例中’本發明之纖維組之纖維具有芯殼型結 構。較佳地，殼層係由聚-L-乳酸、聚（乳酸_共_乙醇酸）或 其混合物構成，且芯層係由聚乙二醇、聚氧化乙烯、 PF1 2 7或含有兩種或兩種以上之上述組份的混合物構成。 本發明提供「類磊晶生長」（epitaxial gr〇wth_like)之超 e\ 鬲員向/、緊毪排列之纖維。根據本發明，本發明之纖維為 定向纖維。在本發明之一實施例中，98%以上之纖維具有 不大於+/· 5。的定向角，且80%以上之纖維具有在〇。至+/_ 2°之範圍内的定向角。 超同對準與緊密排列之中空纖維組之製造 、、可藉由靜電輔助纖維紡絲(包括(但不限於)濕法紡絲、乾 去：絲、電紡絲’料)來製造本發明之纖維組。較佳地 精由電紡絲來製造本發明之纖維組。更佳地，藉由使用 二流體電紡絲頭來形成纖維。 由使用 缺」Ά中’本發明提供—種藉由對聚合溶液進行雷 纺絲來製備本發明之输+ 之進订電 钫絲夕“ 維組的方法’其包含：藉由調整電 增加㈣射纖維之重量，使得在溶液中之^ =化之後’所得纖維之重量為其原始重量的最=- m认去 中之洛劑汽化之後，所得纖維之重詈或甘 原始重量的最少5 S里為其 〇。更佳地，在溶液中之溶冑彳、、_ ，所得纖維之重眚五甘π <岭da化之後 里為其原始重量的40%至95%。更佳地， 145321.doc -12- 201137195 在溶液中之溶劑汽化之後，所得纖維之重量為其原始重量 的 40%至 95%、40%至 90%、45°/。至 90%、50%至 90%、40% 至80%或50%至80%。較佳地’本發明之方法之特徵為： 圍繞作為芯之第二纖維溶液（芯溶液）而對作為殼之第一聚 合溶液（殼溶液）進行同軸電紡絲。 根據本發明，可主要藉由調整溶液之流動速率及濃度來 控制所製造纖維之重量。可使用其他參數以共同控制所製In bio-degradable and/or bioabsorbable polymers containing bioabsorbable and biodegradable linear aliphatic polyesters, such as polyglycolide (PGA) and random copolymers thereof (B-crossing) Ester-co-lactide) (?(} 八_共_ PLA). Food and Drug Administration (F(K)d — Drug has approved the use of these polymers for surgical applications (including for tissue construction) Medical sutures and architectures. The advantage of such synthetic absorbable materials is that they are ultimately metabolized to carbon dioxide and water by simply hydrolyzing degradable degradation products of the vinegar backbone in an aqueous environment such as body fluids, or via the kidneys. Excretion. These polymers are very different from cellulose-based materials, and cellulose-based materials cannot be absorbed by the human body. Other examples of suitable biocompatible polymers are polyhydroxyalkyl methacrylates (including ethyl methacrylate). , and hydrogels (such as polyvinylpyrrolidone, acrylamide, etc.). Other suitable bioabsorbable materials are bio-compounds, including collagen, gelatin, alginic acid, chitin, and poly Glucosamine, fibrin, Uric acid, polydextrose, and polyamino acid. According to the present invention, it is contemplated to use any combination, copolymer, polymer or blend thereof of the above examples. Such bioabsorbable materials can be prepared by known methods. Doc 201137195 Particularly useful biodegradable polymers include poly-lactide, poly-acetazinium, poly 13, and random and block copolymers. Examples of specific polymers include poly d, l-lactide and polylactide-co-glycolide. In another embodiment, the fiber of the fiber group of the present invention has a core-shell structure. Preferably, the shell layer is composed of poly-L- It is composed of lactic acid, poly(lactic acid-co-glycolic acid) or a mixture thereof, and the core layer is composed of polyethylene glycol, polyethylene oxide, PF1 27 or a mixture containing two or more of the above components. The present invention provides "epitaxial gr〇wth_like" super e\ 鬲 向 、 、 、 、 、 、 、 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 More than 98% of the fibers have an orientation angle of not more than +/· 5, and 8 More than 0% of the fibers have an orientation angle in the range of 〇. to +/_ 2°. Manufacture of hollow fiber groups with super-aligned and closely aligned fibers, which can be spun by electrostatically assisted fibers (including (but not Limited to) wet spinning, drying: silk, electrospinning to produce the fiber group of the present invention. Preferably, the fiber group of the present invention is produced by electrospinning. More preferably, by using two fluids. The electrospinning head is used to form a fiber. The invention provides a method for preparing the insulting electric wire of the present invention by thunder spinning the polymerization solution by using the invention. Including: by adjusting the electric power to increase (4) the weight of the fiber, so that after the solution in the solution, the weight of the fiber obtained is the most = - m of the original weight, after the vaporization of the agent, the weight of the fiber obtained Or at least 5 s of the original weight of the glutinous rice. More preferably, the solution in the solution, _, the weight of the resulting fiber is 甘 甘 & 岭 岭 岭 岭 为其 为其 为其 为其 为其 为其 为其 为其 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 More preferably, 145321.doc -12- 201137195 After the solvent in the solution is vaporized, the resulting fiber has a weight of 40% to 95%, 40% to 90%, 45°/ of its original weight. Up to 90%, 50% to 90%, 40% to 80% 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 jointly control
ϋ 造纖維之重量。其他參數包括（但不限於）電紡絲之電壓、 溶液中之溶劑的種類，及收集器與紡絲頭之間的距離。孰 習此項技術者可選擇及/或組合不同參數以達成在溶液‘中 之溶劑汽化之後所得纖維之重量為其原始重量的4〇%至 95°/。的目的。 吾人在此項技術中已知，在電紡絲製程中，可將電紡絲 纖維之形成劃分成三個階段：⑴泰勒錐（Τ咖eQne)階段 ;(2)穩定喷射流階段；及（3)不穩定喷射流階段（2007年的 P〇lymInt 56:1361_1366)。在第-階段，使電力與溶液黏 度及表面張力平衡以形成春勤锆 艰勒錐。當電力大於溶液之表面 張力時，溶液開始自泰勒雜姑 勒錐被拉出且飛行朝向接地目標。 在喷射流飛行現象之第—邮八♦,, 罘°卩分處，纖維擁有初始慣性力且 飛行朝向預定電場之方向。麸 …、肉，Ik者洛劑汽化，噴射流 之重量變得愈來愈小， 纖、准表面上之電荷變得愈來愈大 。不僅法線力會作用於喷射、、ώ d Α 贺射机纖維，而且具有不同方向之 力亦會引起噴射流之側向運 门之 疋莉因此，經噴射敏維推人丁 穩定階段。此等纖維之抨叙p n 、，、進入不 之擺動變得愈來愈大且愈來愈寬。當 145321.doc 201137195 經喷射纖維最終在接地目標上被收集時，以為無規的， 不具向偏好（如在電紡絲之大多數狀況下）。本發明解 、，等問題。& 了獲得具有最大順向之電紡絲纖維，重要 的疋在此等電紡絲纖維進人不穩定狀態之前收集此等電纺 絲纖維。本發明pt立^ 發月已出手思料地發現，在使用本發明之組合 物=% 4絲方法的情況下’經喷射纖維可保持大多數原始 重罝以延續其穩定階段，且在—個纖維緊接另—纖維（亦即 以類猫晶生長」方式）進入不穩定階段之前被收集。 在：發明之方法之一實施例中，使用同軸電紡絲：圍繞 作為心之第二纖維溶液而對作為殼之第一聚合溶液進行電 紡=。經由此製程，將聚合溶液傳送通過同軸紡絲頭。在 貫a例中，一種溶液係由作為外殼層的具有高汽化率之 有機溶劑（較佳地，二氯曱烧（dcm))構成，而另一溶液可 /’、專迖通過内心之非有機溶劑（諸如，水）。在離開紡絲 頭之後，藉由施加電壓來形成泰勒錐。隨著電壓增加，溶 液開始噴射朝向接地收集器。在喷射之早期階段期間（如 在大多數電紡絲製程中），外層之溶劑快速地汽化，從而 留下承〇物之凝固表皮。然而，内層溶劑沒有汽化的機會 匕s於、ΐ喷射纖維之内部。在此等情況下，纖維之重量 保持為其原始重量的50%或60%，且初始慣性力仍為支配 因素’從而使纖維保持在其原始軌跡上穩定地移動。藉助 於旋轉的類轉鼓收集器，此等纖維在同一點處被收集，此 專、截'•隹在；5疋轉方向上彼此重疊。此情形極類似於一些 半 $ 體材料（諸如，GaAs/AlAs、CdSe/CdS、GaN 及 ΖηΟ)之 145321.doc -14- 201137195 蟲晶生長。最後’沖洗掉内部溶液，從而留下超高緊密排 列與順向之中空纖維。 舉例而言’殼溶液之濃度係在6%至25%(w/v)之範圍内 。較佳地，第一溶液之濃度係在13%至20%(w/v)之範圍内 ’更佳地在13%至19%(w/v)之範圍内，且最佳地在15%至 19。/。之範圍内。較佳地，第一溶液及第二溶液含有一或多 種聚合物（較佳地，生物可降解聚合物）。重量 The weight of the fiber. 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. The skilled artisan may select and/or combine different parameters to achieve a weight of the resulting fiber after vaporization of the solvent in solution 'from 4% to 95% of its original weight. the goal of. 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 (eQne) stage; (2) the stable jet stage; 3) Unstable jet flow phase (P〇lymInt 56: 1361_1366, 2007). In the first stage, the power is balanced with the solution viscosity and surface tension to form the Chunqin Zircon. When the power is greater than the surface tension of the solution, the solution begins to pull out from the Taylor awkward cone and fly toward the grounded target. At the point of the jet flow phenomenon, the fiber has an initial inertial force and the flight is in the direction of the predetermined electric field. The bran, meat, and Ik are vaporized, and the weight of the jet becomes smaller and smaller, and the charge on the fiber and quasi-surface becomes larger and larger. Not only the normal force will act on the jet, but also the ώ d Α 贺 机 , , , , , , , , , , , , , , , , , , 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺 贺The entanglement of these fibers, the p n , , and the oscillating movements become larger and wider. When 145321.doc 201137195 was finally collected on the grounding target by the jetted fiber, it was considered to be random and unbiased (as in most cases of electrospinning). The present invention solves the problems, and the like. & The electrospun fibers having the largest forward direction are obtained, and it is important that the electrospun fibers are collected before the electrospun fibers enter an unstable state. The present invention has been found to have found that, in the case of using the composition of the present invention = % 4 wire method, the sprayed fiber can maintain most of the original weight to continue its stable phase, and in the fiber. Immediately before the other fiber (that is, in the form of cat-like growth) is collected before entering the unstable phase. In one embodiment of the method of the invention, coaxial electrospinning is used: electrospinning the first polymerization solution as a shell around a second fiber solution as a heart. Through this process, the polymerization solution is passed through a coaxial spinneret. In the case of a, one solution is composed of an organic solvent having a high vaporization rate as a shell layer (preferably, dichlorohydrazine (dcm)), and the other solution can be used to pass through the inner core. Organic solvent (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 substrate. However, the inner layer solvent does not have the opportunity to vaporize, and the inside of the jetted fiber. 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' to keep the fiber moving steadily over its original trajectory. By means of a rotating drum-like collector, the fibers are collected at the same point, which overlaps each other in the direction of rotation. This situation is very similar to the growth of some semi-materials (such as GaAs/AlAs, CdSe/CdS, GaN, and ΖηΟ) 145321.doc -14- 201137195. Finally, the internal solution is rinsed off, leaving ultra-highly 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 19. /. Within the scope. Preferably, the first solution and the second solution contain one or more polymers (preferably, biodegradable polymers).
在一另外實施例中，芯溶液之流動速率為2…/匕至2〇 ml/hr ’ 較佳地，為 4 ml/hr至 12 ml/hr。 根據本發明，藉由使用合適溶劑以沖洗掉芯來形成中空 纖維。舉例而言，4吏用含水溶劑以移除水溶性聚合物組份 ’而使用有機溶劑以移除水不溶性聚合物組份。 一：圖1中’展示具有轉鼓收集單元之同軸電紡絲設置的 丁-圖《不適於貫踐本文中所描述之方法的電纺絲設置 。電紡絲設置包括具有内管及外管之同軸紡絲頭。怒溶液 二動至内管中，且殼溶液6流動至外管中。電壓充電器產生 益連接至同軸紡絲頭以檢驗電壓。該圖中亦展示泰勒錐。 一根據本發明’所施加之電壓不小㈣kv，以誘使該第 ::及该第二溶液之噴射流以5〇心磁至⑼—η之旋 =度自同轴紡絲頭行進至收集器，以形成纖維組。兩個 二液流動速率與殼溶液流動速率係相當的。溶液 (黏度、傳導率及表面張力）需要處於上文所指定之 一般範圍内。所有、玄该比* 又所扣疋之 例中詳述… 劑形式之聚合物。在諸實 述特疋處理條件。_溶液中之每-者糊流 145321.doc 201137195 體或《心適當流料率傳送至二 ::至紡絲頭之電壓在噴嘴處將不會過快動 流體。藉由使用電子顯微鏡來拍攝纖=拉動 纖維。 〜像而松查所得 中4例： 排列之纖維組可用於各種應用 ’貫心纖維虹可用作實心載體或絕緣材料。 中工纖維組可用於生物技術中。對於包括醫療組織工程( 諸如’架構、神經導引管道及血管導管）及過濾單元之不 同應用彳以各種形狀來製備本發明之超高順向與緊密排 列之中空纖維組。舉例而言，可將本發明之超高順向盥緊 ㈣列之中空.纖維組捲成具㈣中管（tube_in_tube)結構之 V官，其可用作神經導引管道。3外，可將纖維組堆疊以 形成過濾膜。 在一實施例中，用作醫療器件/架構的本發明之超高順 向與緊密排列之中空纖維組可原位用細胞接種’藉以使細 胞懸浮於架構中且暴露至以3_D形式之適當分子嵌入物。 此等細胞接種之中空纖維組可用於組織替換協定中。根據 此實施例’可試管内復原組織，且接著將組織植入至其在 危難中之宿主中。可用的細胞包括神經細胞、上皮細胞、 内皮細胞、纖維母細胞、肌母細胞、軟骨母細胞、骨母細 胞及神經幹細胞。可用於本發明之方法及纖維組中的其他 細胞包括神經賴（Schwann)細胞（WO 92/03536)、星形膠質 細胞、寡樹突神經膠質細胞及其前驅體、腎上腺嗜鉻細胞 I45321.doc 36 201137195 ，及其類似物。 在另一實施例中，本發明之纖維組可形成用作用於過濾 之微過濾膜的多孔膜，更特定言之，中空纖維形式之多孔 水過滤膜。 實例 實例1電紡絲製程 用於製造中空纖維組之材料為聚-L-乳酸（PLLA ; Mw = 140000 Da，日本）、聚乙二醇（PEG ; Mw = 35000 Da， ΟIn a further embodiment, the core solution has a flow rate of from 2.../匕 to 2〇 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' and an organic solvent is used to remove the water-insoluble polymer component. A: Figure 1 'shows a coaxial electro-spinning arrangement with a drum collection unit. The electrospinning setup is not suitable for the method described herein. The electrospinning arrangement comprises a coaxial spinning head having an inner tube and an outer tube. The anger solution is moved into the inner tube, and the shell solution 6 flows into the outer tube. The voltage charger is connected to the coaxial spinneret to verify the voltage. The Taylor cone is also shown in the figure. According to the invention, the applied voltage is not small (four) kv, in order to induce the jet of the first:: and the second solution to travel from the coaxial spinning head to the collection with a rotation of 5 〇 to 7 (9)-η To form a fiber group. The two two-fluid flow rates are comparable to the shell solution flow rate. The solution (viscosity, conductivity and surface tension) needs to be within the general range specified above. All, mysterious ratios* are also deducted. The examples are detailed in the form of polymers. The conditions are dealt with in the details. _ Solution in each of the paste flow 145321.doc 201137195 body or "the proper flow rate of the heart to the second :: the voltage to the spinning head will not be too fast moving fluid at the nozzle. The fiber was taken by using an electron microscope to pull the fiber. ~ For example, 4 cases are obtained: The arranged fiber group can be used in various applications. The core fiber can be used as a solid carrier or insulating material. The medium fiber group can be used in biotechnology. The ultra-highly compliant and closely aligned hollow fiber groups of the present invention are prepared in a variety of shapes for various applications including medical tissue engineering (such as 'architecture, nerve guiding tubing and vascular catheters') and filtration units. For example, the ultrahigh directional (4) hollow hollow fiber bundle of the present invention can be wound into a V official having a (tube) tube_in_tube structure, which can be used as a nerve guiding duct. In addition, the fiber groups may be stacked to form a filtration 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 'by allowing cells to be suspended in the architecture and exposed to appropriate molecules in the form of 3D Embedded. 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 the invention include Schwann cells (WO 92/03536), astrocytes, oligodendrocyte glial cells and precursors thereof, adrenal chromaffin cells I45321.doc 36 201137195, and its analogues. 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. EXAMPLES Example 1 Electrospinning Process The materials used to make the hollow fiber group were poly-L-lactic acid (PLLA; Mw = 140000 Da, Japan), polyethylene glycol (PEG; Mw = 35000 Da, Ο
Sigma-Aldrich)、聚氧化乙烯（ΡΕΟ ; Mw = 900000 Da， Sigma-Aldrich)，且二氯甲烷（DCM; Mallinckrodt，USA)及 N，N-二曱基甲醯胺之溶劑係購自Sigma-Aldrich，Inc^St-Louis, MO) 。 在 無進一 步純化 的情況下以原 樣使用 用於電 紡絲之此等聚合物及溶劑。 PLLA溶液之外殼在以9:1之比的二氯曱烷（DCM)與N，N_ 二曱基曱醯胺（DMF)中自12%(wt/vol)至20%(wt/vol)變化 q (12%、15%、17% 及 20%)。藉由溶解於 10%(wt/vol)之再蒸 .餾水中而獲得含水PEG/PEO(重量比=1:1)溶液。將 PEG/PEO溶液傳送至内芯。用於獲得PLLA/PEG-PEO殼芯 型纖維之電紡絲參數如下：6 cm之間隙距離、14.6 kV之 施加電壓、5 mL/h之内部流動速率、6 mL/h之外部流動速 率、58.5 m/s之收集速率、約68%之相對濕度，及在室溫（ 約25°C)下。 在使用以速率58.5 m/s之旋轉收集器之後，收集 PLLA/PEG-PEO殼芯型纖維以作為超高順向纖維性膜。 145321.doc -17- 201137195 PLLA之濃度愈高，順向就愈高。在將PLLA/PEG-PEO殼芯 型纖維切割成膜片段之後將其置放於再蒸餾水中持續24 hr ，且溶解内芯PEO-PEG纖維，接著製造超高電紡絲中空纖 維。 實例2製備本發明之纖維組 使用連接至高電壓電源之同軸紡絲頭以作為材料分配器 。藉由注射泵，分別以5 ml/hr及4 ml/hr之速率將兩種聚合 溶液（二氣曱烷中之PLLA，wt/vol.為17% ;及去離子蒸餾 水中之PEG/PEO 50/50，wt/vol.為10%)個別地抽汲至同軸 纺絲頭之外管及内管。在施加14 · 6 kV之高電壓之後，自 紡絲頭喷出聚合溶液，且藉由相隔6 cm之旋轉金屬框架來 收集電紡絲纖維。使收集框架以58.5 m/s之速度旋轉。在 25°C之溫度下以68%之相對濕度進行該操作。圖2中展示在 金屬框架上所收集之所得纖維。與通常所見的經收集之電 紡絲纖維之無規擴展模式對比，在極窄範圍上收集此等纖 維。隨著操作時間變得愈來愈長，此等纖維在此極窄範圍 上堆積且最終直立並垂直於收集單元之表面，如在圖3中 所見。接著藉由水來沖洗該等纖維以移除水溶性組份，使 得形成中空結構。在使用掃描電子顯微法進行檢查之後， 觀測到大區域的順向管道之薄片，如圖4所示。引人注目 的是，此等纖維係以之前從未見過之方式完美地附接，如 圖5所示。其係逐個地附接及順向以形成具有單纖維厚度 之薄片。直立膜之高度在不到二十分鐘内可達到2 cm至3 cm(在此狀況下為1 cm)，其中沈積寬度僅為3毫米至4毫米 145321.doc -18- 201137195 . ，如圖4及圖5所示。橫截面視圖展示：該等纖維逐個地緊 铪排列，同時仍具有中空結構之完整性，如圖ό及圖7所示 。先丽研究中從未報告電紡絲纖維順向之此完美性。藉由 影像分析軟體lmagej來測定此等纖維之尺寸。已發現，此 等中空纖維具有19±1.5微米之平均内徑，其中壁厚度為幾 微米。中空纖維之壁為實心的，如圖8所示。 實例3製備本發明之纖維組 0 使用連接至高電壓電源之同軸紡絲頭以作為材料分配器 藉由’主射泵，分別以5 ml/hr及4 ml/hr之速率將兩種聚合 /奋液（一氯甲烷中之PLGA，评^〇1為17% ;及去離子蒸餾 水中之PEG/PEO , wt/v〇l為10%)個別地抽汲至外管及内管 在轭加14.6 kV之高電壓之後，自紡絲頭噴出聚合溶液 ，且藉由相隔6 cm之旋轉金屬框架來收集電紡絲纖維。使 收集框架以58·5 m/s之速度旋轉。在25(5(：之溫度下以68%之 相對濕度進行該操作。藉由SEM來研究電紡絲纖維，如圖 ◎ 9所示。 實例4製備本發明之纖維組 使用連接至高電壓電源之同軸紡絲頭以作為材料分配器 。藉由注射泵，分別以5 ml/hr& 4 ml/hr之速率個別地抽汲 兩種聚合溶液（DCM/DMF : 9/1 中之PLLA/PF127，「60/40重 畺比」，17 wt0/〇 ;及去離子蒸館水中之peg/peo : 50/50 ’ wt/ό) °在施加ΐ4·6 kV之咼電壓之後，自紡絲頭噴出聚 合溶液，且藉由相隔1〇 cm之旋轉金屬框架來收集電紡絲 纖維。使收集框架以58.5 m/s之速度旋轉。在25t之溫度 H5321.doc •19- 201137195 I以68%之相對濕度進行該操作。在藉由去離子蒸餾水進 丁中洗以#除水Ά性組份之後，所得薄膜不僅揭露中空纖 而且揭路多孔壁結構，如圖10所示。達成高定向，如 圖1所不，然而，其不與先前狀況下一樣明顯。此等中空 纖：之直徑係在數十微米之範圍内，其中壁厚度為幾微米 。精由Image〗軟體來特性化多孔壁結構，且發現微孔大小 在人微米至4微米之範圍内。初步渗透測試確認壁内之微 孔的連續性。亦檢驗：&等多孔中线維可容易地渗透液 體。圖12及圖13為自具有相同操作參數之類似組合物所獲 得之電紡絲纖維的。 實例5使用具有各種濃度之聚合溶液來製備本發明之纖 維組 材料及方法類似於實例}之材料及方法，且僅改變pLLA 洛液之濃度。藉由使用具有6 wt%、8 wt%、1〇 wt%、15 wt%、17〜％及19 wt%之pLLA之濃度的殼pLLA溶液已 觀測到，當溶液具有6 wt%至1〇 wt%之較低濃度時，經收 集之纖維組圍繞收集轉鼓之表面散佈。在較高濃度（15%至 1 6%)下，此等纖維開始集中至極窄點，且最終當流動速率 比達到17%及19%時直立’如圖14所示。圖15展示自以下 不同濃度所製備之PLLA中空纖維性膜的SEM影像：（a)8 wt0/〇 ; (b)12 wt% ; (c)15 wt% ; (d)16 wt% ; (e)l7 wt% ;及 (f)l9 wt%。隨著濃度增加，纖維展現較佳順向及較緊密排 列。在濃度為19 wt%的情況下，PLLA電紡絲中空纖維組 具有最高順向’如圖16所示。 145321.doc -20- 201137195 具有各種流動逮率之聚合溶液來製備本發明 :料及方法類似於實例,之材料及方法，其中僅改變内 口 P /谷液之流動速率。葬由祐田。 ^精由使用8 w/v。/。之PLLA溶液以作為Sigma-Aldrich), polyethylene oxide (ΡΕΟ; Mw = 900,000 Da, Sigma-Aldrich), and the solvent of dichloromethane (DCM; Mallinckrodt, USA) and N,N-dimercaptocaramine 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 dichlorodecane (DCM) to N,N-didecylguanamine (DMF). q (12%, 15%, 17% and 20%). An aqueous PEG/PEO (weight ratio = 1:1) solution was obtained by dissolving in 10% (wt/vol) 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 to serve as ultra-high directional fibrous membranes. 145321.doc -17- 201137195 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 production of ultra-high electrospun hollow fibers. Example 2 Preparation of the fiber group of the present invention A coaxial spinning head connected to a high voltage power source was used as a material dispenser. The two polymerization solutions (PLLA in dioxane, 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 pumped 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 spinning head, 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, the 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 to form a hollow structure. After inspection using scanning electron microscopy, a large section of the straight tube of the tube 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 after the other 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, and the deposition width is only 3 mm to 4 mm 145321.doc -18-201137195 . And Figure 5 shows. The cross-sectional view shows that the fibers are aligned one after the other while still having the integrity of the hollow structure, as shown in Figure 7 and Figure 7. This perfection of electrospinning fibers has never been reported in the research of Xianli. The size of these fibers was determined by the image analysis software lmagej. 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 Fiber Groups of the Invention 0 A coaxial spinning head connected to a high voltage power source was used as a material dispenser by a 'primary injection pump, respectively, at a rate of 5 ml/hr and 4 ml/hr. The liquid (PLGA in methyl chloride, 17% of the evaluation of 〇1; and PEG/PEO in deionized distilled water, 10% of wt/v〇l) was individually twitched to the outer tube and the inner tube was added to the yoke. After the high voltage of 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 a speed of 58·5 m/s. This operation was carried out at a relative humidity of 68% at a temperature of 25 (5): The electrospun fiber was studied by SEM as shown in Fig. 9. Example 4 Preparation of the fiber group of the present invention was carried out using a connection to a high voltage power source. The coaxial spinning head was used as a material dispenser. The two polymerization solutions were separately pumped by a syringe pump at a rate of 5 ml/hr & 4 ml/hr (PLLM/PF127 in DCM/DMF: 9/1, respectively). "60/40 weight ratio", 17 wt0/〇; and peg/peo in deionized steaming water: 50/50 'wt/ό) ° After applying a voltage of ·4·6 kV, spun from the spinning head The solution was polymerized and the electrospun fibers were collected by a rotating metal frame spaced 1 cm apart. The collection frame was rotated at 58.5 m/s. At 25 t, H5321.doc •19- 201137195 I was 68% relative. Humidity is carried out. After dewatering the water to remove the hydrophobic component by deionized distilled water, the obtained film not only reveals the hollow fiber but also reveals the porous wall structure, as shown in Fig. 10. A high orientation is achieved, as shown in Fig. 1 no, however, it is not as obvious as in the previous situation. These hollow fibers: the diameter is in the tens of micro Within the range, where the wall thickness is a few micrometers, the porous wall structure is characterized by Image software, and the pore size is found in the range of human micrometers to 4 micrometers. Initial penetration test confirms the continuity of micropores in the wall. It is also checked that the porous centerline dimension can easily penetrate the liquid. Figures 12 and 13 show the electrospun fibers obtained from similar compositions having the same operating parameters. Example 5 uses a polymerization solution having various concentrations. The fiber group material and method of the present invention are prepared similarly to the materials and methods of the example, and only the concentration of the pLLA solution is changed. By using 6 wt%, 8 wt%, 1 wt%, 15 wt%, 17~ A shell pLLA solution having a concentration of % and 19 wt% of pLLA has been observed, and when the solution has a lower concentration of 6 wt% to 1 wt%, the collected fiber group is scattered around the surface of the collecting drum. At concentrations (15% to 16.6%), the fibers begin to concentrate to a very narrow point and eventually erect when the flow rate ratio reaches 17% and 19%, as shown in Figure 14. Figure 15 shows the preparation from the following different concentrations. SEM image of PLLA hollow fiber membrane: (a) 8 Wt0/〇; (b) 12 wt%; (c) 15 wt%; (d) 16 wt%; (e) l7 wt%; and (f) l9 wt%. As the concentration increases, the fiber exhibits better yield. The alignment is relatively tight. At a concentration of 19 wt%, the PLLA electrospun hollow fiber group has the highest forward direction as shown in Fig. 16. 145321.doc -20- 201137195 Polymerization solution with various flow rates The present invention is prepared: The materials and methods are similar to the examples, materials and methods in which only the flow rate of the inner port P/cold solution is varied. It was buried by Youtian. ^ Fine by using 8 w/v. /. The PLLA solution is used as
叙材料且在5 ml/hr之怪定流動速率下傳送該溶液咖容 液之内部流動速率自5ml/hr增加至12mi/hr。已觀測到， 當流動速率比低(亦即，1祕H.6爲)時，經收集之 纖維組圍繞收集轉鼓之表面散佈。在較高流動速率比^ ml/hr至2.0 ml/hr)下，此等纖維開始集中至極窄點，且最 終當流動速率比達到2.2及2.4時直立，如圖17所示。隨著 内部流動速率增加’纖維亦展現較佳順向及較緊密排列， 如圖18所示，圖18提供自以下不同流動速率比所製備之 PLLA中空纖維性膜的SEM影像：（a)1 2;(叩6 ml/hr ’（c)2_〇 ml/hr ;及⑷2.4 ml/hr。如圖19所示，在流 動速率比為2.4 ml/hr的情況下，PLLA電紡絲中空纖維組具The internal flow rate of the material was transferred from 5 ml/hr to 12 mi/hr at a strange flow rate of 5 ml/hr. It has been observed that when the flow rate ratio is low (i.e., 1), the collected fiber groups are scattered around the surface of the collecting drum. At higher flow rate ratios from ^ml/hr to 2.0 ml/hr, the 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 directional 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; (叩6 ml/hr '(c) 2_〇ml/hr; and (4) 2.4 ml/hr. As shown in Figure 19, PLLA electrospinning at a flow rate ratio of 2.4 ml/hr Hollow fiber assembly
實例6使用 之纖維組 有最高順向。 實例7結合各種電壓使用具有各種流動速率之聚合溶液 來製備本發明之纖維組 圖20提供聚焦紡絲纖維之施加電壓及重量之因素的操作 圖。使具有不同 PLLA濃度（8 wt%、10 wt%、12 wt%、15 wt%、17 wt%及19 wt%)之一系列溶液經受自0 kV/cm至4 kV/cm的場強度之增加。將開始自泰勒錐拉動纖維時之場 強度記錄為下限臨界極限。當場強度太高而導致纖維崩潰 或引起顯著擺動時，將該場強度標記為上限場強度極限。 145321.doc -21 - 201137195 此圖展示藉由上限電壓極限 區心目… 限及下限電麼極限所分離之三個 Α θ )。下文描述—實例紡絲條件。在15糾％之 Α洛液及15kv之電壓的纺絲條件下，隨著電廢增加， =絲纖維開始自紡絲頭右側之泰勒錐拉動，當 =，纖維㈣喷射朝向接地端。首先，飛行之纖維移 妾地目‘。在開始時，在區域I中，溶液黏度足夠 1而防止溶液被較小靜電力拉動。隨著㈣增加且達 狀界值’在區域η中，此等纖維被連續地形成且飛行朝 向接地Μ票。在電力及纖維之剩餘重量的導引下，此等纖 維之緊密排列及直立膜之生長變得可能。然而，隨著電壓 連續地增加，在區域ΠΙ中，電力變成支配力，從而引起纖 維之擺動（有時引起主要經嘴射溶液之無規擴展）。如由圖 21所♦曰不’用於膜之形成的下限臨界電壓亦處於與溶液黏 度之下限臨界電壓相同的趨勢。應注意，自紡絲頭相當容 易地實現早期階段纖維之形成（諸如，8〜以至12 wt%)， 然而，僅在施加某靜電的情況下（甚至在極低電壓下）可能 存在極佳的緊密排列。此操作圖提供關於製造超高順向與 緊密排列之膜的可用導引。 實例8細胞成活力檢定 自臺北醫學牙齒銀行與牙齒幹細胞技術中心（Center 〇f Taipei Medical Teeth Bank and Dental Stem Cell Technology)獲得初級臼齒。自切除之牙齒提取牙髓，且以 機械方式將牙髓切碎並以0.25%之胰蛋白酶_ EDTA(Invitr〇gen，Carlsbad, CA)在37°C下處理牙髓持續15 145321.doc -22- 201137195 min。使用吸液管來濕磨牙髓細胞之所得混合物。在37°C 下使用相等體積的0.5 mg/mL之胰蛋白酶抑制劑 (Invitrogen)及 2000 U/mL之去氧核糖核酸酶I(Sigma，St· Louis，MO)來處理離散細胞持續1 5 min之後，將牙髓懸浮 液在1 500 rpm下離心持續5 min，且捨棄上澄液。 為了測試PLLA電紡絲中空纖維組之生物相容性，遵循 ISO 10993 標準程序（Sasaki, R.等人之 2008 年的 Tubulation with dental pulp cells promotes facial nerve regeneration in rats· Tissue Engineering - Part A.(14(7):第 1141-1147 頁）） ，且將DPSC在PLLA架構中培育6天。結果展示：細胞成 活力接近於對照群組之細胞成活力，此暗示無細胞毒性， 如圖22所示。 【圖式簡單說明】 圖1展示具有轉鼓收集單元之同軸電紡絲設置之電紡絲 的示意圖，該同軸電紡絲設置適於實踐本發明之方法。 Q 圖2展示在本發明之旋轉收集器上所收集的本發明之「 直立」纖維的實體外觀。 圖3展示經收集之直立PLLA纖維性膜的（a)側視圖及（b) 俯視圖。 圖4展示超高順向與緊密排列之中空PLLA中空纖維的大 區域。 圖5展示超高順向與緊密排列之中空PLLA纖維（細節）。 圖6展示超高順向與緊密排列之PLLA中空纖維的SEM攝 影（展示橫截面及表面兩者）。 145321.doc -23- 201137195 圖7展示超高順向與緊密排列之電紡絲PLLA中空纖維（ 詳細地展示橫截面）。 圖8展示具有實心壁之電紡絲PLL A中空纖維之交叉視圖 的SEM攝影。 圖9展示電紡絲PLGA中空纖維之交叉視圖的SEM攝影。 圖1 0展示具有多孔壁之電紡絲PLLA中空纖維的SEM攝 影（俯視圖）。 圖11展示具有多孔壁之電紡絲PLLA中空纖維的SEM攝 影（橫截面視圖）。 圖12展示具有多孔壁之電紡絲PLLA中空纖維的SEM攝 影（細節）。 圖13展示具有多孔壁之電紡絲PLLA中空纖維的SEM攝 影。 圖14展示自以下不同濃度所製備之經收集之電紡絲 PLLA中空纖維的實體外觀：（a)6 wt% ; (b)8 wt% ; (c)15 wt% ;及（d)19 wt0/〇。 圖1 5展示自以下不同濃度所製備之PLL A中空纖維性膜 的3£1^影像（在300倍之放大率下）：（&)8\^%;(1))12诃1%; (c)15 wt% ; (d)16 wt% ; (e)17 wt% ;及（f)19 wt°/。。樣本在 20秒之週期内被收集。 圖16展示自不同濃度所製備之PLLA中空纖維性膜的纖 維順向。 圖1 7展示自以下不同流動速率比所製備之經收集之電紡 絲PLLA中空纖維的實體外觀：（a) 1.2 ml/hr ; (b) 1.6 ml/hr 145321.doc -24- 201137195 . ;(c)2.0 ml/hr ;及（d)2.4 ml/hr。 圖18展示自以下不同FRR^/。；)所製備之plla中空纖維性 膜的SEM影像（在300倍之放大率下）：（a)i ; (b)1.4 ; (c)1 8 ;(d)2.0 ; (e)2.2 ;及⑴2.4。樣本在20秒之週期内被收集。 圖19展示自不同流動速率比（流進/流出）所製備之PLLa 中空纖維性膜的纖維順向。 圖20展示聚焦紡絲纖維之施加電壓及重量之因素的操作 圖0 〇 田 ® 21展示聚合溶液之濃度與該溶液之黏度之間的關係。 圖22展示對照群組及PLLA群組中之DPSC的細胞成活力 (n=9) ° 〇 145321.doc -25-The fiber group used in Example 6 had the highest orientation. Example 7 The use of a polymerization solution having various flow rates in combination with various voltages to prepare the fiber group of the present invention. Fig. 20 is an operation diagram for providing factors for applying voltage and weight of the focused 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. 145321.doc -21 - 201137195 This figure shows three Α θ ) separated by the limit of the upper limit voltage limit zone and the limit of the lower limit. Described below - example spinning conditions. Under the spinning condition of 15 %% of Α洛液 and 15kv voltage, as the electric waste increases, the = silk fiber starts to pull from the Taylor cone on the right side of the spinning head. When =, the fiber (4) is sprayed toward the ground. First of all, the flying fiber moves to the ground. At the beginning, in zone I, the solution viscosity is sufficient to prevent the solution from being pulled by a smaller electrostatic force. As (4) increases and reaches the threshold value 'in the region η, these fibers are continuously formed and fly toward the grounded ticket. The tight alignment of these fibers and the growth of the erect membranes are possible under the guidance of the remaining weight of electricity and fibers. However, as the voltage continuously increases, in the region ΠΙ, the electric power becomes dominant, causing the fiber to oscillate (sometimes causing a random expansion of the main nozzle solution). The lower limit threshold voltage used for the formation of the film as shown in Fig. 21 is also in the same tendency as the lower limit threshold voltage of the solution viscosity. It should be noted that the spinning of the early stage makes it easy to achieve the formation of fibers in the early stages (such as 8 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 guidance on the fabrication of ultra-highly compliant and closely aligned membranes. Example 8 Cell Viability Assay Primary caries were obtained from the Center 〇f 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 (Invitr〇gen, Carlsbad, CA) at 37 ° C for 15 145321.doc -22 - 201137195 min. A pipette was used to wet the resulting mixture of dental pulp cells. Treatment of discrete cells for 15 min at 37 °C using an equal volume of 0.5 mg/mL trypsin inhibitor (Invitrogen) and 2000 U/mL deoxyribonuclease I (Sigma, St. Louis, MO) Thereafter, the pulp suspension was centrifuged at 1 500 rpm for 5 min, and the supernatant was discarded. In order to test the biocompatibility of the PLLA electrospun hollow fiber group, 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): Pages 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. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a schematic view of electrospinning with a coaxial electrospinning arrangement of a drum collection unit that is adapted to practice the method of the present invention. Q 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 shots (showing both cross-section and surface) of ultra-high forward and closely aligned PLLA hollow fibers. 145321.doc -23- 201137195 Figure 7 shows ultra-high forward and closely aligned electrospun PLLA hollow fibers (detailed in cross section). Figure 8 shows an SEM photograph of a cross-sectional view of an electrospun PLL A hollow fiber having a solid wall. Figure 9 shows SEM photography of a cross-sectional view of an electrospun PLGA hollow fiber. Figure 10 shows an SEM shot (top view) of an electrospun PLLA hollow fiber having a porous wall. Figure 11 shows an SEM shot (cross-sectional view) of an electrospun PLLA hollow fiber having a porous wall. Figure 12 shows an SEM shot (detail) of an electrospun PLLA hollow fiber having a porous wall. Figure 13 shows an SEM shot of an electrospun PLLA hollow fiber having a porous wall. 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 wt0 /〇. Figure 15 shows a 3 £1 image of a PLL A hollow fiber membrane prepared at different concentrations (at 300 magnifications): (&) 8\^%; (1)) 12诃1% (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 145321.doc -24-201137195 . (c) 2.0 ml/hr; and (d) 2.4 ml/hr. Figure 18 shows the different FRR^/ from the following. ;) SEM image of the prepared plla hollow fiber membrane (at 300 times magnification): (a) i; (b) 1.4; (c) 1 8 ; (d) 2.0; (e) 2.2; (1) 2.4. Samples were collected over a 20 second period. Figure 19 shows the fiber orientation of the PLLa hollow fiber membrane prepared from different flow rate ratios (flow in/out). Figure 20 shows the operation of the factors of the applied voltage and weight of the focused spun fiber. Figure 0 〇田 ® 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) ° 145 145321.doc -25-