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Thermo-Sensitive Hydrogel Encapsulating N-Phenacylthiazolium Bromide for Facilitating the Recovery of Experimental Periodontitis: An Assessment from the Micro-Computed Tomography

N-苯甲酰噻唑溴化物體溫感應凝膠修復實驗型牙周炎破壞之微電腦斷層影像評估

摘要


研究顯示使用N-苯甲酰噻唑溴化物(N-phenacylthiazolium bromide, PTB)截斷最終糖化蛋白(advanced glycation end-products),可有效控制牙周發炎。本研究旨在製備體溫感應凝膠攜帶PTB以修復牙周炎組織。凝膠以Carboxymethyl-hexanoyl chitosan為基底、加入β-甘油磷酸鈉、甘油、及PTB製成,並於體外環境下進行成膠測試。動物實驗則在大鼠口內分側製造實驗型牙周炎,並於復原期分為4組:沒有牙周炎的控制組、牙周炎但無投予凝膠、牙周炎並投予未含藥物的凝膠、及牙周炎並投予含有PTB 的凝膠。動物於治療後第14天犧牲,並於不同階段照射微電腦斷層,觀察腭側及牙齒鄰接面牙周附連齒槽骨復原。實驗結果發現凝膠在37°C迅速膠化,並藉由附連齒槽骨顯著的喪失(p < 0.001),證實實驗型牙周炎已成功誘發。PTB治療在復原期第4天及14天,相對於投予未含PTB凝膠組別有顯著較少附連齒槽骨喪失 (p < 0.05),鄰接面處附連齒槽骨喪失之改善亦較腭側為之顯著。基於上述結果可知,此體溫感應凝膠攜帶PTB 可加速實驗型牙周炎齒槽骨修復,具發展為輔助牙周治療試劑之潛力。

並列摘要


Background: 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 thermo-sensitive hydrogel encapsulating N-phenacylthiazolium bromide (PTB), an AGE breaker, in order to effectively facilitate the recovery of periodontitis in vivo. Materials and Methods: A hydrogel composed of carboxymethyl-hexanoyl chitosan polymer, β-glycerol phosphate, glycerol, and PTB was fabricated, and the gelation time under 4 and 37°C was evaluated in vitro. Experimental periodontitis was induced by submerging 4-0 silk suture in the gingival sulcus on the Sprague-Dawley rats. After silk suture removal, and the sites were divided into 4 groups with a split-mouth design, including (1) control group without periodontitis induction (Group C), (2) experimental periodontitis (Group W), (3) experimental periodontitis plus hydrogel (Group H), (4) experimental periodontitis plus hydrogel with PTB (Group P) (n = 6 per group/per time). Periodontal bone loss (PBL) was evaluated by micro-computed tomography on the baseline and 0, 4 and 14 days after silk suture removal (p > 0.05). Results: The hydrogel was fluidic at 4°C but was gelled immediately at 37°C. PBL was significantly increased after 7-days ligature placement (p < 0.001), indicating that experimental periodontitis was successfully induced. PBL was significantly reduced in Group P relative to that in Group H at days 4 and 14 (p < 0.05 & p < 0.05), and the reduction was apparently greater in the interproximal area relative to that in the radicular area. Conclusions: A thermo-sensitive hydrogel encapsulating PTB was successfully fabricated and was favorable in facilitating the recovery of experimental periodontitis.

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