【作者】 徐晓薇； 顾中一； 林崇韬； 孙宏晨；

【Author】 Xiaowei Xu;Zhongyi Gu;Chongtao Lin;Hongchen Sun;Department of Periodontology,School and Hospital of Stomatology,Jilin University;State Key Laboratory of Supramolecular Structure and Materials,College of Chemistry,Jilin University;Department of Oral Pathology,School and Hospital of Stomatology,Jilin University;

【机构】 吉林大学口腔医学院牙周病科； 吉林大学超分子结构与材料国家重点实验室； 吉林大学口腔医学院病理科；

【摘要】 目的:制备阿司匹林碳量子点和可注射温敏型水凝胶,考察牙周炎模型下,载Aspirin和EPO的可注射温敏型水凝胶促牙周组织再生作用。方法:以阿司匹林为原料合成碳点;制备载Aspirin和EPO的温敏型水凝胶。通过透射电镜、紫外和XPS等表征材料的理化性质。体内、外通过HE染色、Elisa、Real-time PCR、激光共聚焦显微镜等检测Aspirin碳点抗炎及成像作用。同时,体内建立大鼠牙周炎模型,Micro-CT结合HE染色检测缺损处牙周组织再生情况。结果:透射电镜下观察所合成的阿司匹林碳点尺寸为3-5nm;体外Real-time PCR结果显示,在LPS刺激RAW264.7细胞诱导炎症环境下,阿司匹林药物与阿司匹林碳点均可抑制炎症因子的产生,其中阿司匹林碳点对IL-1β、TNF-α和MMPs的抑制作用要优于单纯阿司匹林药物(P<0.05)。体内HE染色结果显示:与空白对照组相比,Aspirin组和Aspirin碳点组炎症反应不明显,仅有少量散在分布的中性粒细胞浸润。Micro-CT结果显示,与空白对照组相比,牙周炎组第一、二磨牙间牙槽骨高度、BMD、BV/TV等指标明显降低,载Aspirin和EPO水凝胶组牙槽骨高度、BMD、BV/TV等指标降低小于载Aspirin组、载EPO组和单纯水凝胶组。HE染色结果显示,与空白对照组相比,牙周炎组釉质牙骨质界到牙槽嵴顶间距离明显增大,载Aspirin和EPO水凝胶组增大距离小于载Aspirin组、载EPO组和单纯水凝胶组。此外,牙周炎组淋巴细胞、浆细胞浸润明显多于其它组。结论:基于阿司匹林的碳量子点具有较好的生物相容性,既保留了抗炎作用,又可用于生物成像。载Aspirin和EPO的可注射温敏型水凝胶能够控制牙周炎症,促进牙周组织再生。更多还原

【Abstract】 Objectives:Regeneration of periodontium is still challenging for the clinician,since there is little achievement on the regulation of periodontitis niche.In this study,the periodontium regeneration ability of an injectable and thermosensitive hydrogel with controlled-release of aspirin-based carbon dots and EPO is studied in vivo to reveal their potential in periodontium regeneration.Methods:The carbon dots(CDs) were prepared by pyrolysis of aspirin.In vitro anti-inflammatory effect of aspirin and CDs was compared by quantitative real-time polymerase chain reaction using RAW264.7 cell line.The periodontium regeneration ability of an injectable and thermosensitive hydrogel with controlled-release of aspirin-based carbon dots and EPO was evaluated by Micro-CT and HE staining using an established periodontitis model.Results:The size of CDs observed by transmission electron microscopy were 3～5 nm.Anti-inflammatory effect of CDs was more obvious than that of aspirin by measuring pro-inflammatory cytokines(IL-1β,TNF-α and MMP-9) under stimulation of LPS.Furthermore,MicroCT results showed that injectable and thermosensitive hydrogel with controlled-release of aspirin-based carbon dots and EPO could inhibit alveolar bone loss with a higher BMD and BV/TV level.HE staining results indicated that injectable and thermosensitive hydrogel with controlled-release of aspirin-based carbon dots and EPO group showed smaller distance between the cemento-enamel junction(CEJ) and the apex of alveolar bone,and less lymphocytes and plasmocytes were detected.Conclusions:Our results demonstrate that aspirin-based carbon dots have dual functions of cellular imaging and anti-inflammation,injectable and thermosensitive hydrogel with controlled-release of aspirin-based carbon dots and EPO could inhibit periodontitis and promote periodontium regeneration.更多还原