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系統識別號 U0026-1108201013204200
論文名稱(中文) 以力學觀點評估傷口注射膠原蛋白、透明質酸及明膠對皮膚癒合的影響
論文名稱(英文) Mechanical Evaluations of the Influence of Collagen, Hyaluronan and Gelatin Injections on Skin Wound Healing
校院名稱 成功大學
系所名稱(中) 醫學工程研究所碩博士班
系所名稱(英) Institute of Biomedical Engineering
學年度 98
學期 2
出版年 99
研究生(中文) 陳慶頤
研究生(英文) Ching-Yi Chen
學號 p8697421
學位類別 碩士
語文別 中文
論文頁數 72頁
口試委員 口試委員-黃玲惠
口試委員-林真福
口試委員-吳建一
指導教授-葉明龍
中文關鍵字 傷口癒合  生物性材料  拉伸強度  膠原蛋白  明膠  透明質酸 
英文關鍵字 Wound Healing  Biomaterials  Tensile Strength  Collagen  Hyaluronan  Gelatin 
學科別分類
中文摘要 術後加速傷口癒合且減小疤痕大小一直是學者積極努力的目標。在過去,已有多種物理性刺激因子與敷傷材料被研究其對傷口癒合的影響;然而,鮮少研究以皮膚的力學性質作為傷口癒合指標。多種生物性材料已作為臨床上的使用,本研究使用大鼠傷口模型,將膠原蛋白(Collagen)、明膠(Gelatin)與透明質酸(HA)與其複合物等不同生物性材料注射於縫合的傷口,在1、2、4、6與8週分別以拉力測試測量皮膚拉伸強度作為皮膚癒合指標、使用組織切片染色了解癒合組織生長情況以及膠原蛋白定量觀察胞外基質的生成情況。
結果發現材料注射會有不同的疤痕外觀。癒合初期傷口在在單一材料注射會有縫線疤痕;複合材料則是有較大且向內微凹的傷疤。癒合晚期則複合材料有較相似於正常皮膚之外觀。力學性質恢復得知,HA較所有材料注射組有較高的力學性質恢復情況,其他組彼此間均無其差異性。組織切片觀察顯示,單一材料有較快的表皮恢復情況且真皮層組織內部結構較為緻密;複合材料則是具有較於相似正常皮膚真皮組織細部的構型。於組織內膠原蛋白生成量比例結果發現,除單一材料於癒合時期2週Gelatin與HA組有較高的分泌量之外,彼此間無明顯差異。
綜合以上結論發現,單一材料對於癒合初期表皮癒合與再上皮化程度提供顯著效果;癒合初期具有較佳的傷口密合,癒合晚期擁有較佳的皮膚拉伸強度與恢復情況,但存在隱約縫線的縫線疤痕。複合材料作用效果可能著重於癒合後期真皮結構的加速新生與重組。
英文摘要 Quick and smooth skin healing is the goal in wound healing researches. In the past, several physical stimulating factors and wound dressing materials have been studied for their influences on wound healing. However, only few studies investigated the mechanical recovery of healing wound. Several biological materials have been used in clinical practice. Natural materials such as Type I collagen, Hyaluranon (HA), gelatin and their composite are similar to the composition of natural skin and have beneficial potential in cell proliferation, differentiation and ECM synthesis at wound sites. So far, no research has reported the mechanical recovery of the healing skin by injecting those natural biomaterials directly into the wound site. The aim of this study was to investigate the mechanical recovery influences of injectable biomaterials such as collagen, HA, gelatin and their composite on incisional wound injury in rat model. Tensile strength of healing skin was measured at 1, 2, 4, 6 and 8 weeks after incision; than, the correlated recovery index was calculated. The architecture of skin-wound was observed with histological section and collagen synthesis was measured.
The results showed that different biomaterial injection provided different scar pattern. Mono biomaterial groups had suture-scar pattern and mixed biomaterial groups had sunken scar pattern. The HA group had the best recovery results of mechanical properties compared with other groups. Histological observations exhibited that mono biomaterial groups had faster epidermis recovery and more compact dermis architecture. The mixed group had similar dermis architecture to normal skin. Collagen synthesis ratio showed that Gelatin and HA group had a higher collagen content at 2 weeks of healing time. Overall, mono biomaterial had significant effects on epithelial wound healing and re-epithelialization during early stage. In the late stage, the skin had a better tensile strength and recovery index, but there were slight suture-scar at wound site. Effect of mixed biomaterials might focus on regeneration and remodeling of the architecture of skin-wound.
論文目次 中文摘要 I
Abstract II
致謝 IV
目錄 VI
圖目錄 VIII
表目錄 X
第一章 緒論 1
1.1皮膚的結構、組成與功能 1
1.1.1表皮層 (Epidermis layer) 2
1.1.2真皮層 (Dermis layer) 3
1.1.3皮下組織 (Hypodermis layer) 5
1.2實驗鼠與人類皮膚結構的差異性 7
1.3皮膚的傷口癒合過程 8
1.3.1發炎期 (Inflammatory phage) 8
1.3.2生長期 (Proliferation phase) 9
1.3.3成熟期 (Maturation phase) 10
1.4傷口修復之動物模型 10
1.4.1急性傷口模型(Acute wound models) 11
1.4.2慢性傷口模型(Chronic wound models) 11
1.4.3癒合能力受損模型(Impaired healing models) 11
1.5參與傷口癒合之細胞外基質-膠原蛋白、明膠與透明質酸 12
1.5.1膠原蛋白(Collagen) 12
1.5.2明膠(Gelatin) 14
1.5.3透明質酸(Hyaluronic acid or Hyaluronan) 15
1.6相關文獻探討 17
1.6.1實驗變數因子正規化與實驗流程標準化 17
1.6.2透明質酸對傷口癒合之影響 18
1.6.3膠原蛋白對傷口癒合之影響 19
1.6.4明膠對傷口癒合之影響 19
1.7研究動機 20
1.8研究目的 20
第二章 材料與方法 21
2.1實驗設計 21
2.2實驗材料與設備 23
2.2.1生物性材料 23
2.2.2試片裁切器與夾具 23
2.2.3拉力測試機台 24
2.2.4照相擷取系統 24
2.3實驗方法 25
2.3.1動物實驗 25
2.3.2標準試片準備 26
2.3.3抗拉強度試驗 28
2.3.4膠原蛋白成分分析 29
2.3.5組織切片染色 29
2.3.6統計分析 30
第三章 結果 31
3.1實驗一部分-單一材料 31
3.1.1不同癒合時間之傷口外觀 31
3.1.2不同單一生物性材料與不同癒合時間對癒合皮膚的影響 32
3.1.3組織切片觀察 38
3.1.4組織內膠原蛋白生合成變化量之觀察 41
3.2實驗第二部分-複合材料 42
3.2.1不同癒合時間之傷口外觀 42
3.2.2 不同複合生物性材料與不同癒合時間對癒合皮膚的影響 43
3.2.3組織切片觀察 49
3.2.4組織內膠原蛋白生合成變化量之觀察 52
3.3 單一生物性材料 與 複合生物性材料之結果 比較 53
3.3.1 不同材料對癒合傷口外觀之影響 53
3.3.2 不同癒合時間之癒合皮膚抗拉強度與癒合皮膚癒合指數比較 55
3.3.3 組織切片觀察 58
3.3.4組織內膠原蛋白生合成變化量之觀察 61
第四章 討論 63
4.1不同材料對癒合傷口外觀之觀察 63
4.2不同材料對皮膚力學性質恢復之影響 63
4.3不同材料對癒合皮膚組織內部之影響 64
4.4不同材料對組織內膠原蛋白生合成變化量之影響 65
4.5實驗限制 66
4.5.1實驗對象選擇與樣本標準化 66
4.5.2 動物模型與傷口模型的選擇 66
4.5.3 皮膚試片的處理 67
4.6未來研究 67
第五章 結論 69
參考文獻 70
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