傳統的傷口敷料既不能促進癒合傷口的細胞活動，也不能監測傷口癒合的過程。更換敷料會破壞傷口癒合的進程，且易造成病人患部的疼痛。在傷口癒合的過程中，病原體感染會導致H2O2過度釋放，使傷口持續處於發炎階段，延緩傷口的癒合。在本研究中，我們製備了一種具有底部導電層和頂部視覺輔助監測層的複合水凝膠敷料，用於加速傷口的癒合及監測。利用羧甲基纖維素(Carboxymethyl cellulose, CMC)來修飾苯胺(Aniline, AN)，並摻入丙烯醯胺(Acrylamide, AM)製備出導電水凝膠片。接著以溶劑型水熱合成法合成出Co-SrVxOy 金屬氧化物微米粒子(MPs)，再與丙烯醯胺(AM)混合，製備出PAM-Co-SrVxOy 水凝膠作為監測層。最後以計時安培分析法(chronoamperometry)的方式進行測量。本研究分為三個部分，在材料方面，我們成功的將CMC接枝在PANI上，合成出親水性的CMC-PANI導電性高分子，再與PAM交聯後製備出導電性水凝膠片。監測層水凝膠片在不同濃度的H2O2水溶液中有靈敏的顏色變化。透過循環伏安圖顯示了Co-SrVxOy MPs在H2O2存在下的氧化電位，使用計時安培分析法測量監測層水凝膠片在H2O2水溶液中的電化學響應，以建立針對H2O2濃度的校正曲線。在細胞實驗中，我們以Elution Test方法證實了導電水凝膠片、Co-SrVxOy MPs及監測層水凝膠片的生物相容性。在動物實驗中，利用具有全層皮膚缺損的小鼠模型中進行評估。導電水凝膠片提供了內源性生物電信號傳輸到傷口的通道，電刺激宿主細胞的遷移與增生，加速受傷組織的修復；監測層水凝膠片對正常和感染傷口中不同的H2O2濃度顯示出顏色變化的響應。以上實驗結果可知，本論文所開發出的導電水凝膠片可以加速傷口癒合，且監測層水凝膠片可利用顏色變化來區別正常傷口及感染傷口的不同，從而警告患者潛在的感染。基於兩種功能水凝膠的潛力，在未來可以整合成一套傷口監測系統，用於無創實時監測傷口癒合的進程。

Traditional wound dressings neither promote the cellular activities that heal wounds nor facilitate monitoring of wound healing. Repeated dressing changes can disrupt the wound healing process and easily cause discomfort to the patient's affected area. In the process of wound healing, infection from pathogens causes excessive release of H2O2, which prolongs the inflammation stage and delays healing. In this study, we prepared a composite hydrogel dressing with a bottom electrical conducting layer and a top visual-aid monitoring layer to expedite wound healing. Carboxymethyl cellulose-grafted-aniline (CMC-PANI) was prepared as a conductive polymer and combined with polyacrylamide (PAM) to form a conductive hydrogel layer (CMC-PANI/PAM), while Co-SrVxOy metal oxide microparticles (MPs) were synthesized and trapped in PAM hydrogel as the monitoring layer (PAM-Co-SrVxOy). The MPs are oxidized in the presence of H2O2, resulting in visual green to orange colored response, which was also quantified by electrochemical signals such as chronoamperometry. The efficacy of the composite dressing was evaluated in a mouse model with a full-thickness skin defect. The conductive hydrogel provides a channel that transmits the endogenous bioelectrical signal to the wound and accelerating the restoration of the wounded tissue. The monitoring hydrogel showed a good color response to varying H2O2 concentrations in a normal and infected wound, thereby warning patients of a potential infection. The composite hydrogel can be integrated into a wound monitoring system in the future, for noninvasive real-time monitoring of the healing progress.

目錄
摘要 II
Abstract III
目錄 IV
圖錄 VI
第一章 緒論 1
1.1 皮膚組織與傷口的癒合階段 1
1.2 傷口癒合中的內源性電場(Endogenous Electric Fields) 4
1.3 傷口癒合與活性氧物質之關係 5
1.4 傷口監測與評估 7
1.5 CMC-PANI/PAM導電水凝膠之介紹 7
1.5.1 CMC-PANI導電性高分子 7
1.5.2 PAM聚合物 8
1.6 Co-SrVxOy 金屬氧化物微米粒子材料之介紹 9
1.6.1 過渡金屬氧化物 (Transition metal oxides) 9
1.6.2 缺氧 (Oxygen Deficiency) 10
1.6.3 鍶 (Strontium) 10
1.6.4 釩 (Vanadium) 10
1.6.5 鈷 (Cobalt) 11
1.7 PAM-Co-SrVxOy 水凝膠之介紹 12
1.8 循環伏安法 (Cyclic voltammetry) 12
1.9 計時電流法 (Chronoamperometry) 12
1.10 研究動機與實驗目的 13
1.11 實驗架構圖 14
2.1 實驗材料 15
2.2 CMC-PANI 導電性高分子 16
2.2.1 CMC-PANI 導電性高分子的製備 16
2.2.2 CMC-PANI 導電性高分子的結構分析 16
2.3 CMC-PANI/PAM 導電水凝膠 16
2.3.1 CMC-PANI/PAM 導電水凝膠的製備 16
2.3.2 CMC-PANI/PAM 導電水凝膠之特性分析 16
2.3.3 CMC-PANI/PAM 導電水凝膠之導電度測試 17
2.3.4 CMC-PANI/PAM 導電水凝膠之拉力分析 17
2.4 Co-SrVxOy 金屬氧化物微米粒子 (MPs) 17
2.4.1 Co-SrVxOy MPs 的合成 17
2.4.2 Co-SrVxOy MPs 之結構分析 18
2.4.3 Co-SrVxOy MPs 之特性分析 18
2.4.4 Co-SrVxOy MPs 之H2O2靈敏度測試 18
2.4.5 Co-SrVxOy MPs 之循環伏安法測試 19
2.4.6 Co-SrVxOy MPs 之計時安培分析法測試 19
2.5 PAM-Co-SrVxOy 水凝膠 19
2.5.1 PAM-Co-SrVxOy 水凝膠的製備 19
2.5.2 PAM-Co-SrVxOy 水凝膠之H2O2靈敏度測試 20
2.5.3 PAM-Co-SrVxOy 水凝膠之計時安培分析法測試 20
2.6 In vitro study 20
2.6.1 細胞培養 20
2.6.2 細胞存活率分析 21
2.7 In vivo study 21
2.7.1 動物實驗 21
2.7.2 傷口閉合率(wound closure) 21
2.7.3 H2O2靈敏度測試 22
第三章 實驗結果與討論 23
3.1 CMC-PANI 導電性高分子的結構分析 ( FTIR、XRD ) 23
3.2 CMC-PANI/PAM 導電水凝膠 24
3.2.1 CMC-PANI/PAM 導電水凝膠之特性分析(SEM) 24
3.2.2 CMC-PANI/PAM 導電水凝膠之導電度分析 25
3.2.3 CMC-PANI/PAM 導電水凝膠之拉力分析 26
3.3 Co-SrVxOy 金屬氧化物微米粒子 (MPs) 27
3.3.1 Co-SrVxOy MPs 之特性分析 ( SEM、TEM、XRD、XPS ) 27
3.3.2 Co-SrVxOy MPs之H2O2靈敏度測試 31
3.3.3 Co-SrVxOy MPs之循環伏安法測試 32
3.3.4 Co-SrVxOy MPs 之計時安培分析法測試 32
3.4 PAM-Co-Sr Vx Oy 水凝膠 33
3.4.1 PAM-Co-SrVxOy 水凝膠之H2O2靈敏度測試 33
3.4.2 PAM-Co-SrVxOy 水凝膠之計時安培分析法測試 33
3.5 體外實驗 34
3.5.1 細胞存活率分析 34
3.6 體內實驗 35
3.6.1 傷口閉合率(wound closure) 35
3.6.2 H2O2靈敏度測試 36
第四章 結論 37
參考文獻 38
 

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