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標題: | N-苯甲酰噻唑溴化物之發炎敏感性凝膠於修復牙周病破壞的成效評估 Recovery of Periodontal Destruction by Using An Inflammation-Responsive Hydrogel Encapsulating N-Phenacylthiazolium Bromide |
作者: | Min-Chen Yu 余敏甄 |
指導教授: | 張博鈞(Po-Chun Chang) |
關鍵字: | 凝膠,N-苯甲??唑溴化物,牙周炎,傷口修復, hydrogel,periodontitis,N-phenacylthiazolium bromide,wound healing, |
出版年 : | 2015 |
學位: | 碩士 |
摘要: | 牙周病是一種細菌誘發之傳染性疾病,會造成牙齦發炎、骨頭喪失、牙齒動搖、最後導致牙齒的喪失。如何有效的抑制發炎反應,減少牙周病的破壞,進而促進牙周組織的再生一直是牙周病治療的目標。有很多證據顯示牙周病和糖尿病之間有相互作用的關係,亦有研究指出使用N-苯甲酰噻唑溴化物(N-phenacyl- thiazolium bromide, PTB)以截斷最終糖化蛋白(advanced glycation end-products (AGEs))的產生可有效控制牙周發炎的狀況。本研究旨在製備一個對發炎反應及體溫敏感之凝膠用以攜帶PTB、並透過動物實驗探討此凝膠修復牙周炎組織之可行性。凝膠以Carboxymethyl-hexanoyl chitosan (NOCHC) polymer為基底,並加入β-glycerol phosphate disodium salt (β-GP)、甘油(glycerol)、及PTB製成,並在體外環境針對不同溫度凝膠之成膠時間(gelation time)、及不同酸鹼值PTB之釋放進行觀察。動物實驗方面,使用大鼠做為口腔分側實驗(split-mouth design),並分為四組:(1)沒有製造牙周發炎的控制組(Group C),(2)製造牙周發炎,但是沒投予凝膠(Group W),(3) 製造牙周發炎,投予未含藥物的凝膠(Group H),(4)製造牙周發炎,投予含有PTB的凝膠(Group P)。牙周發炎是在大鼠上顎第二大臼齒,使用4-0的絲線纏繞。七天後使用牙周翻瓣手術將線移除並且同時投予凝膠。等待四天以及十四天後把老鼠犧牲,觀察組織切片。並且於實驗前,絲線移除前,移除絲線後四天及十四天照射微電腦斷層觀察牙周附連之齒槽骨復原的情形。
實驗結果發現在pH5.5~6.5時,PTB會快速大量從凝膠中釋放。在中性環境下釋放較為緩慢且持久。動物實驗則可觀察到絲線纏繞七天後,和控制組(Group C)相比有明顯的牙周附連之齒槽骨喪失(p<0.001),證實牙周炎已被成功誘發。PTB治療組別(Group P) 則在術後四天及十四天,相對於未投予PTB凝膠的組別(Group H)有較少的牙周附連齒槽骨喪失(p<0.05)。組織學觀察發現相較於未給予凝膠(Group W)或未投予PTB之組別(Group H),PTB治療組別(Group P)於移除絲線後四天顯著降低發炎細胞之浸潤(p<0.01&p<0.001),此顯著降低之發炎亦延續至移除絲線後十四天(p<0.01 & p<0.05)。觀察膠原纖維基質(collagen fiber matrix)之分布,亦發現PTB治療組別於移除絲線後四天和十四天均有相較於未投予凝膠的組別(Group W)(p<0.001 & p<0.001)及未給予PTB治療組別(Group P)(p<0.01 & p<0.001)有較緻密及規律之膠原纖維排列。 基於上述結果可知,以NOCHC為基底之凝膠具備發炎敏感及溫度感應特性,此凝膠攜帶PTB可加速牙周炎組織復原之過程。 Background:Ample evidences demonstrated a close inter-relationship between diabetes and periodontitis, the blockade of advanced glycation end-products (AGEs) has been suggested as a feasible approach to control the inflammatory destruction of periodontitis. This study was purposed to develop a pH-responsive hydrogel encapsulating N-phenacylthiazolium bromide (PTB), an AGE breaker, in order to effectively facilitate the recovery of periodontitis in vivo. Materials and Methods:A chitosan-based hydrogel encapsulating PTB was fabricated, and the in vitro release profile under pH 5.5-7.4 was evaluated. Twelve Sprague-Dawley rats were utilized and divided into 4 groups with a split-mouth design, including (a) control group without periodontitis induction (Group C), (b) experimental periodontitis (Group W), (c) experimental periodontitis plus hydrogel (Group H), (d) experimental periodontitis plus hydrogel with PTB (Group P). Experimental periodontitis was induced by submerging 4-0 silk in the gingival sulcus for 7 days, and hydrogel was delivered after silk removal. Periodontal bone loss (PBL) was evaluated by micro-computed tomography in baseline and 0, 4 and 14 days after silk removal, and histology was evaluated at 4 and 14 days. Results:Initially burst release of PTB was noted in pH 5.5-6.5, whereas the release was relatively slow and consistent in the neutral environment. PBL was significantly increased after 7-days ligature placement (p<0.001). PBL was significantly reduced in the PTB group relative to hydrogel-treated alone group at day 4 and 14 (p<0.05 & p<0.05), and the remission of collagen matrix was significantly in the PTB group relative to experimental periodontitis and hydrogel-treated alone groups at both day 4 (p< 0.001 & p< 0.01) and day 14 (p< 0.001 & p< 0.001). The extent of inflammatory cells infiltration was significantly reduced in the PTB group relative to the experimental periodontitis and hydrogel-treated alone groups at both day 4 (p< 0.01 & p< 0.001) and 14 (p< 0.01 & p< 0.05). Conclusions:An inflammation-responsive and thermo-sensitive hydrogel encapsulating PTB was successfully fabricated and was favorable in facilitating the recovery of periodontal destruction. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53653 |
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顯示於系所單位: | 臨床牙醫學研究所 |
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