設計開發一多效複合式殼聚醣水凝膠用於慢性傷口修復之研究

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林聖喆(Sheng-Jhe Lin) 查詢紙本館藏

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生物醫學工程研究所

論文名稱

設計開發一多效複合式殼聚醣水凝膠用於慢性傷口修復之研究
(Development of a Multifunctional Chitosan-Based Hydrogel Dressing for Chronic Wound Healing)

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至系統瀏覽論文 (2026-11-1以後開放)

摘要(中)

慢性傷口的定義是傷口經過適當的治療後不能達到結構和外部癒合。當病灶暴露時，人體皮膚上的主要病灶細菌金黃色葡萄球菌大量增殖，減緩皮膚創面的恢復。含銀離子敷料是慢性傷口敷料發展的主流，但近年來，許多研究指出銀離子對細胞有一定程度的毒性損傷。銀離子並不是抗菌敷料的唯一選擇，抗生素的使用也因耐藥性問題而受到限制。然而，聚六亞甲基雙胍（PHMB）已被證明不僅對皮膚細胞的細胞毒性低，而且對細菌有良好的抑制作用。在傷口癒合方面，表皮生長因子 (EGF) 刺激人體角質形成細胞增殖。本研究開發了一種由凍融法合成的敷料，通過殼聚醣的化學聚合和物理相互作用製備了含有 PHMB 和 EGF 奈米顆粒的高強度殼聚醣/PVA 水凝膠。與無載體組相比，EGF-奈米粒子延長了EGF的釋放時間，隨著EGF濃度的增加，對角質形成細胞的生長有顯著的正面影響。根據文獻指出，氧氣對於傷口上微血管的生成具有幫助，所以本研究也將PFOB奈米粒子加入水膠中，使得水膠具有攜帶氧氣的能力。我們的研究顯示了物理分析、機械性能、抗菌、抗炎作用以及氧氣攜帶的能力。這種水凝膠作為主要的敷料材料，創造了一個有助於傷口修復的濕潤環境，不僅具有良好的抗菌作用，而且還具有促進病灶細胞生長的能力，並提供多於正常狀態下的氧氣含量來促進微血管生成。未來，我們預計這種水凝膠可以顯著提高慢性傷口癒合的治療效果。

摘要(英)

The definition of chronic wound is that the wound cannot achieve structural and external healing after proper treatment. When the lesion is exposed, Staphylococcus aureus, the main lesion on human skin, proliferates in large quantities, slowing the recovery of the skin wound. Dressings containing silver ions are the mainstream of the development of dressings for chronic wounds, but in recent years, many studies have pointed out that silver ions have a certain degree of toxic damage to cells. Silver ions are not the only option for antibacterial dressings, and the use of antibiotics is also restricted due to drug resistance issues. However, polyhexamethylene biguanide (PHMB) has been proven not only to have low cytotoxicity to skin cells, but also to have a good inhibitory effect on bacteria. In wound healing, epidermal growth factor (EGF) stimulates the proliferation of human keratinocytes. In this study, a dressing synthesized by the freeze-thaw method was developed, and a high-strength chitosan/PVA hydrogel containing PHMB and EGF nanoparticles was prepared through the chemical polymerization and physical interaction of chitosan. Compared with the carrier-free group, EGF-nanoparticles prolonged the release time of EGF. As the concentration of EGF increased, it had a significant positive effect on the growth of keratinocytes. According to the literature, oxygen is helpful for the formation of microvessels on the wound, so this study also added PFOB nanoparticles to the hydrogel to make the hydrogel have the ability to carry oxygen. Our research shows physical analysis, mechanical properties, antibacterial, anti-inflammatory and oxygen carrying capacity. As the main dressing material, this hydrogel creates a moist environment that helps wound repair. It not only has a good antibacterial effect, but also has the ability to promote the growth of lesion cells and provides more than normal oxygen content. To promote microangiogenesis. In the future, we expect that this hydrogel can significantly improve the therapeutic effect of chronic wound healing.

關鍵字(中)

★ 水凝膠
★ 慢性傷口癒合
★ 抗菌
★ 增殖
★ 表皮生長因子
★ 聚已亞甲基鹽酸

關鍵字(英)

★ Hydrogel
★ Chronic wound healing
★ Antibacterial
★ Proliferation
★ EGF
★ PHMB

論文目次

第一章緒論……………....……………………………1
第二章研究背景……………………………..….……3
2.1慢性傷口介紹………………………………………………3
2.1.1靜脈性潰瘍…………..………...…...……………..………3
2.1.2糖尿病性潰瘍….……………....…………………...…….4
2.1.3壓瘡性潰瘍……...……………………………......…….4
2.2 慢性傷口可能導致的併發症……….…….…......….…...………5
2.2.1潰瘍………………………………...…...……………..………6
2.2.2蜂窩性組織炎………..……….....…...………………..………6
2.2.3敗血症…….………...………...…...…………………..………7
2.3慢性傷口臨床治療方式…………..……………………..…..8
2.3.1清創 (Debridement)…………….......…...……………….……8
2.3.2外科手術清創(Surgical Debridement)……….…………..……9
2.3.3自溶性清創 (Autolytic Debridement)……….…..…........……9
2.3.4酵素清創(Enzymatic Debridement)..…...…………….....……9
2.3.5生物性清創(Biological Debridement)…....….…………..……9
2.3.6高壓氧治療(Hyperbaric Oxygen Therapy)…….……..……10
2.4傷口護理及傷口敷料………………………………………….10
2.4.1傳統紗布……………………………...….…………………11
2.4.2藻酸鹽敷料……………………… ………….……………..11
2.4.3薄膜性敷料……………………………………………….…12
2.4.4泡沫性敷料……………………………..………….……..13
2.4.5水膠主體敷料……………………..…….…….…………14
2.4.6水凝膠型敷料…………………………………..………15
2.4.7生物性敷料……………………………………………..16
2.5傷口癒合的機至與進程發展….…….……………………...17
2.5.1炎症期………………………………………………….....17
2.5.2增生(擴散)期…………………………………..……..…...….18
2.5.3重塑期………………………………………………….....18
2.6 殼聚醣(Chitosan)………………….…….………….….....…...20
2.7聚乙烯醇(PVA)…………………….…………...………………20
2.8 Cosmocil CQ……….……………….…………..……………...22
2.9 全氟辛基溴(PFOB)……..………………….…..………….….23
2.10 表皮生長因子(Epidermal Growth Factor, EGF)……….…..…24
第三章實驗部分………………………………..……………….25
3.1實驗藥品、材料及儀器…………………………….…...………25
3.1.1藥品及材料…….……………………………….…………33
3.1.2儀器…………………………..……………………………27
3.1.3縮寫對照表…………………………..……………………28
3.2檢量線…………….…………….…………….…….…………...29
3.2.1 ELISA檢測表皮生長一子標準曲線.………………………29
3.2.1 ELISA檢測IL-8發炎因子準曲線.………………………29
3.2.1 UV-vis檢測Cosmocil CQ標準曲線.………………………30
3.3實驗整體流程………………...…………………….………...…32
3.4 EGF奈米粒子製備…………….………………….…….….....32
3.5 PFOB奈米粒子製備……………….…………………………34
3.6 CTENPs & PFNPs物理&化學特性分析………………………35
3.6.1粒徑分析……………………….…………………………35
3.6.2表面電位分析………….……………..……………………35
3.6.3超高真空場發射掃描式電子顯微鏡(FE-SEM)拍攝……..35
3.6.4包覆率分析………………………….……………………35
3.6.5負載率分析………………………..………………………36
3.7 配製3% Chitosan………………………………..………….....36
3.8配製10% PVA…………………………....……..……………...36
3.9 製作貼片型水膠CPCEPG(含有CTENPs、PFNPs、CQ).……37
3.10 EGF的體外釋放……………….…..………………………...37
3.11 CQ的體外釋放………….…………………….………….…38
3.12氧氣的體外釋放……………………………...….………….…38
3.13熱重儀分析(TGA)……………………...……….………….….39
3.14抗菌試驗-抑菌圈………………..…………….……………….39
3.15抗菌試驗-點盤…..……………………...……….………….….41
3.16細胞毒性試驗…...……………………...……….………….….42
3.17細胞生長試驗…...……………………...……….………….….43
3.18抗發炎能力試驗……………………...……….………….….44
3.19機械性質測試(抗拉強度及延伸率)…...……….………….….45
3.20 C PCEPG之膨潤度與含水率測試…………….………….….46
3.21動物試驗…….……………………...……….………….….47
3.22統計與分析…….……………………...……….………….….47
第四章結果與討論…………………………………..48
4.1 CTENPs & PFNPs物理及化學性質…….…………...………48
4.2 CTENPs & PFNPs之表面形態分析……………..……………49
4.3 CPCEPG之表面型態分析……………………...….………….49
4.4 CPCEG對於金黃色葡萄球菌抗菌實驗……………………...51
4.4.1 細菌的抑制圈………….…………………….………….…51
4.4.2 細菌菌落的點盤實驗….…………………….………….…52
4.5 CPCEG的CQ體外毒性試驗……………………...………..….53
4.6 人類角質形成細胞之細胞生長實驗…………………...……...54
4.7 CPCEG-GA之抗發炎能力測試………….………….….......…..56
4.8 CPCEPG之體外釋放氧氣試驗…………………………………57
4.9 CPCEPG之TGA結構分析…………………………….……....58
4.10 CPCEPG之機械性質測試(延伸率、抗拉強度)……...…..…59
4.11 CPCEPG之膨潤度及含水率……..…….……........................60
4.12動物實驗………………………………...…………….…….…61
4.13組織切片分析…………………………...…………….…….…64
第五章結論………………………………………………..66
第六章未來展望…….……..………………………………67
參考文獻…………………..………..……………..………..…68

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指導教授

李宇翔(Yu-Hsiang Lee)

審核日期

2021-10-27

推文