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研究生:鄭惠文
研究生(外文):Hui-Wen Cheng
論文名稱:第一型膠原蛋白結合玻尿酸作為注射性皮膚軟組織填充物之合成及動物實驗評估
論文名稱(外文):Hyaluronic acid-coupled type I Collagen as Injectable Filler Substance for Soft Tissue Augmentation in Skin
指導教授:王盈錦
指導教授(外文):Yng-Jiin Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:93
中文關鍵詞:膠原蛋白透明質酸
外文關鍵詞:collagenhyaluronic aciddermal filler
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有越來越多新的注射性皮膚填充物進入醫學美容市場,但沒有一項符合理想性填充物的條件。目前也沒有很好的動物模式來評估這些新材料的生物相容性、安全性、持續性及有效性並。本研究主要原理在探討以紐西蘭大白兔動物模式,評估是以膠原蛋白為結構主體,利用N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide (EDC)為活化劑,將透明質酸以共價鍵方式和膠原蛋白偶合成分子複合共聚物作為注射性皮膚填充物,評估其體內生物相容性(Biocompatibility)及堅持度(Persistency):製備材料上,膠原蛋白重組時,使用高pH (8.5)、低濃度(0.5mg/ml)的參數,可使製造出的膠原纖維較細,藉此可改善注射性。動物實驗模組主要為評估植入材料的堅持度(persistency)和生物相容性(biocompatibility)。植入期間利用超音波評估,可清楚看見植入材料呈現低回響(hypoechoic)及一中間穿越的假影(speed artifact)。植入材料體積可藉由長度及高度衡量後計算所得並分析。膠原纖維及透明質酸混合物體積降解率最高;交聯濃度最高的體積降解率最低。組織切片堅持度分析部份,因單一切面關係,可立體評估的超音波較好。至於生物相容性的部份,實驗室中所製備材料和市售材料相比,呈現良好生物相容性(good biocompatibility)
More and more novel dermal fillers enter the expanding beauty market, but none of them fulfill the criteria of the ideal fillers. There is also no ideal animal model well accepted for the evaluation of increasing new products. The goal of the experiment was to establish a short term animal model using New Zealand(NZ) rabbit for the evaluation of biocompatibility and persistency of the fillers, which we have prepared collagen modified with hyaluronic acid by different concentration (1mM, 10mM and 25mM) of EDC ( N-(3-Dimethylaminopropyl) - N-ethylcarbodiimide ).
We found that collagen at lower concentration (0.5mg/ml) and at higher pH(pH8.5) reconstituted into finer fibrils. With this reconstitution condition we fabricated 5 different samples according to the concentration of EDC. Injectability of these fillers were smooth with intermittent spikes.. We use ultrasound system to evaluate the volume change of the implanted sites after 0.1 ml of each sample was injected on the ear of the NZ rabbit. The space of the implanted dermal filler showed hypoechoic with intervening speed artifact. The volume degradation rate was more prominent in the sample with no HA modification and the persistency was better in the sample , which has the highest concentration of crosslinker (EDC). Due to the limitation of histological evaluation, ultrasound is better than histological analysis for evaluating persistency . As for biocompatibility, the fillers we fabricated in the laboratory exhibited relatively good biocompatibility as compared to the commercial product.
關鍵詞(Keywords):collagen, hyaluronic acid, dermal filler, biocompatibility, persistency, histological analysis, ultrasound system
目 錄
英文摘要 I
中文摘要 II
目 錄 III
表 目 錄 V
圖 目 錄 VI
第一章、緒論 1
1-1注射性皮下軟組織填充物 1
1-2皮膚結構介紹及老化造成皮膚的變化 3
1-3膠原蛋白 11
1-4透明質酸 16
1-5市場上現行皮下軟組織填充物的種類及應用 21
1-6 研究動機與目的 24
第二章、實驗藥品與器材 26
2-1實驗藥品 26
2-2實驗儀器 27
2-3動物實驗器材與藥品 28
第三章、實驗方法 29
3-1膠原蛋白純化 29
3-2第一型膠原蛋白重組製備膠原纖維 30
(COLLAGEN FIBRIL) 30
3-2-1重組製備 Fibril 30
3-2-2 製備 Type I Collagen fibril & HA混合物 31
3-2-3 製備 Type I Collagen fibril & HA 偶合物 32
3-3膠原蛋白濃度測定(LOWRY’S方法) 34
3-4膠原蛋白重組SEM及TEM 35
3-5滅菌方式 37
3-6注射性測定 (INJECTABILITY TEST) 39
3-7動物實驗 39
3-8組織切片、脫水、染色及評估 42
3-8-1組織取樣及包埋方式 42
3-8-2組織脫水 43
3-8-3組織切片染色 43
3-8-4組織切片的評估-堅持度及生物相容性 44
3-9超音波觀察及評估 47
3-9-1 超音波觀察 47
3-9-2 超音波評估 49
第四章、結果與討論 50
4-1注射性皮膚軟組織填充物的製備 50
4-2膠原蛋白纖維與透明質酸偶合物及混合物的分析 51
4-3注射性測驗 (INJECTABILITY TEST) 57
4-4材料成品及動物實驗外觀 58
4-5超音波分析皮內注射膠體隨天數變化情形 61
4-6組織切片分析皮內注射膠體隨天數變化情形 65
4-6-1 堅持度評估 (persistency) 65
4-6-2生物相容性評估 (biocompatibility) 70
第五章、結論 75
第六章、參考文獻 78
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