靜電紡絲奈米纖維由於孔徑小、孔隙率高、表面積大，作為傷口敷料時表現出優異的性能。石蓴多醣由於具有較高的生物相容性和豐富的抗菌、抗氧化等生物活性，被廣泛應用於生物醫學領域，然而，其生物活性很容易受到萃取過程的影響，此外，在大多數溶劑中的低溶解度以及較差的流變性能，使其不利於電紡；因此，本研究旨在探討萃取溶劑或透析對石蓴多醣 (ulvan) 的影響，接著在水/甲醇系統中，將石蓴多醣摻入溫感性幾丁聚醣/聚(氮-異丙基丙烯醯胺-共-氮-羥乙基丙烯醯胺) [chitosan/poly(N-isopropyl acrylamide-co-N-hydroxyethyl acrylamide), CS/PNIHE] 奈米纖維中，或在水/丙酮/四氫呋喃系統中直接與 PNIHE 混合，此外，還將評估纖維型態，探討其促進傷口癒合的潛力。用 HCl、NaOH 和 ddH2O 萃取石蓴多醣，並以透析進行純化，所有萃取物均具有典型的石蓴多醣結構，且鼠李糖為主要的單醣，並在 200 ℃ 內顯示出良好的穩定性，而酸萃取能產生低分子量、高鼠李糖含量且抗氧化能力佳的石蓴多醣，雖然透析能有效提高純度，但考慮到產率及硫酸根含量，將選用酸萃取未透析的石蓴多醣添加到後續製備的奈米纖維中；為了持續遞送石蓴多醣並增強奈米纖維在水溶液中的穩定性，採用兼具溫感性和熱交聯特性的 PNIHE 作為電紡載體材料，經 1H NMR 確認合成的 PNIHE 鏈段比與入料比相近，其濁點溫度 (cloud point, TCP) 會隨著氮-羥乙基丙烯醯胺含量的增加而增加，當氮-異丙基丙烯醯胺和氮-羥乙基丙烯醯胺入料比為 9：1 (PNII9HE1) 時，具有接近體溫的 TCP；在水/甲醇系統中，使用 3：7 (v/v) 的 5% (w/v) CS 乙酸水溶液和 30% (w/v) P(NI9HE1) 甲醇溶液，電紡出含有珠狀結構的纖維，平均直徑為 172.7 ± 76 nm，然而，由於缺乏有效的交聯方法，無法摻入石蓴多醣；在水/丙酮/四氫呋喃系統中，使用 3：7 (v/v) 的 2% (w/v) 石蓴多醣水溶液和 30% (w/v) P(NI9HE1)丙酮/四氫呋喃 (1/4) 溶液，成功電紡出光滑均勻的纖維，平均直徑為 142.8 ± 68.8 nm。綜上所述，本研究成功篩選出萃取石蓴多醣並摻入溫感性電紡奈米纖維的最佳條件，之後將持續研究有效的交聯方法，以增加作為傷口敷料的潛力。

Electrospun nanofibers have small pore size, high porosity, large surface area, and exhibiting excellent performance as wound dressings. Ulvan, due to high biocompatibility and rich biological activities such as antibacterial and antioxidant properties, is widely used in the biomedical field. However, its biological activities are easily affected by extraction processes. Besides, its limited solubility in most solventsand poor rheological properties make it unfavorable for electrospinning. Therefore, this study aims to explore the effects of extraction solvents or dialysis on ulvan, followed by incorporating ulvan into thermosensitive chitosan/poly(N-isopropyl acrylamide-co-N-hydroxyethyl acrylamide) (CS/PNIHE) nanofibers in water/methanol system or directly mixed with PNIHE in water/acetone/tetrahydrofuran system. Additionally, fiber morphology will be assessed and explored for its potential to promote wound healing. Ulvan was extracted by HCl, NaOH and ddH2O, and purified by dialysis. All extracts had typical ulvan structures, with rhamnose as the main monosaccharide, and exhibited good stability up to 200 ℃. Acid extracted ulvan has low molecular weight, high rhamnose content, and good antioxidant activity ulvan. Although dialysis could enhance purity, taking into account yield and sulfate content, undialyzed ulvan extracted with acid would be added to the subsequently prepared nanofibers. To achieve continuous delivery of ulvan and enhance the stability of nanofibers in aqueous solution, PNIHE, possessing both thermosensitive and thermal crosslinking properties, was used as the electrospinning carrier material. The synthesized PNIHE was confirmed by 1H NMR, indicated a chain ratio similar to the feed ratio. The cloud point temperature (TCP) of PNIHE increased with an increase in the content of N-hydroxyethyl acrylamide. When the feed ratio of N-isopropyl acrylamide and N-hydroxyethyl acrylamide was 9:1 (PNII9HE1), the TCP was close to body temperature. In water/methanol system, nanofibers were electrospun using 5% (w/v) CS acetic acid aqueous solution and 30% (w/v) P(NI9HE1) methanol solution at 3:7 (v/v) ratio. SEM images revealed that the nanofibers contained bead structure with an average diameter of 172.7 ± 76 nm. However, Ulvan couldn't be incorporated due to the lack of effective crosslinking methods. In the water/acetone/tetrahydrofuran system, nanofibers were electrospun using 2% (w/v) ulvan aqueous solution and 30% (w/v) P(NI9HE1) acetone/tetrahydrofuran (1/4) solution at 3:7 (v/v) ratio. SEM images revealed that the nanofibers had a smooth and uniform structure with an average diameter of 142.8 ± 68.8 nm. In summary, this study successfully screened out the optimal conditions for extracting ulvan, and incorporating into thermo-sensitive electrospun nanofiber. Furthermore, we would study effective crosslinking methods continuously in the near future to increase the potential as a wound dressing.

摘要 I
Abstract II
Graphic abstract III
目錄 i
圖目錄 iii
表目錄 v
附錄目錄 vi
第一章、前言 1
第二章、文獻回顧 3
2.1 皮膚 3
2.2 創傷敷材 7
2.3 靜電紡絲 8
2.4 石蓴多醣 18
2.5 幾丁聚醣 21
2.6 聚(氮-異丙基丙烯醯胺) 及其共聚物 22
第三章、實驗動機與目的 24
第四章、實驗流程 25
第五張、材料與方法 26
5.1 實驗材料 26
5.2 實驗藥品 26
5.3 實驗儀器 28
5.4 實驗溶液配製 30
5.5 實驗方法 32
第六章、結果與討論 40
6.1 石蓴多醣之萃取與性質分析 40
6.2 石蓴多醣之生理活性 50
6.3 PNIHE 之合成與性質分析 56
6.4 溫感性奈米纖維之製備 64
第七章、結論 74
第八章、未來工作 75
第九章、參考文獻 76
第十章、附錄 91
10.1 石蓴多醣之萃取 91
10.2 石蓴多醣之分子量檢量線 93
10.3 石蓴多醣之單醣組成 94
10.4 石蓴多醣之抗菌活性 95
10.5 石蓴多醣於 DEME 的溶解情形 98
10.6 石蓴多醣於甲醇中的溶解度 98
10.7 奈米纖維之交聯 99

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