新型防龋智能材料调节口腔菌群作用的研究

Developing new generation of biomaterials that maintain ecological balance of oral microbiota has been the research hot spots in caries prevention and treatment fields. Smart materials are among the new frontiers in the anti-caries materials research. Traditional pH-sensitive materials have various problems including complex synthesis and design, short-term effect and that they are difficult to realize in situ drug loading in oral envirionment. To solve the current problems encountered by pH-sensitive materials, the tertiary amine materials were designed and synthesized by the principle of "protonation-deprotonation" and based on the quaternary ammonium materials widely studied in our previous studies. Based on that, this project aims to develop novel anti-caries smart materials, to realize intraoral in situ drug loading through the repeatability of non-release pattern and "protonation-deprotonation"; to comprehensively evaluate their anti-caries effect using in vitro models and animal models; to explore their intelligent pH-sensitive mechanisms in vitro by investigating their anti-biofilm effects under different pH conditions. Besides, combined with traditional biocompatibility tests and "oral-gut flora" stability investigations, the biological safety of novel anti-caries smart material will be comprehensively evaluated. Meanwhile, antibacterial mechanism, as well as induction mechanism and removal strategies of emerged drug resistant and persistent bacteria during the application of the smart materials will also be analyzed. Collectively, all the efforts will help lay a solid foundation for the sustainable development of novel smart pH-sensitive anti-caries materials.

维持口腔菌群平衡的新型生物材料是龋病防治研究的难点和热点。智能材料的开发是目前防龋材料突破的新方向。传统pH敏感材料存在着合成设计复杂，作用不持久，难以在口内环境实现原位载药等问题。本项目针对当前pH敏感材料遇到的问题，以前期研究的季铵盐材料为模板，利用“质子化-去质子化”原理，设计合成相应的叔胺材料。在此基础上，研究合成新型防龋智能材料，通过非释放型和“质子化-去质子化”的可重复性实现口内原位载药；利用体外模型和动物模型全面评价防治龋病作用；并通过在不同pH环境中对牙菌斑生物膜的作用，探究其体外智能pH敏感机制；结合传统生物安全性检测和“口腔-肠道菌群”稳定全面评估新型防龋智能材料的生物安全性；同时探索新型防龋智能材料的抗菌机制，以及耐药菌和持留菌产生机制和清除方法，为防龋智能材料的可持续发展奠定基础。

维持口腔菌群平衡的新型生物材料是龋病防治研究的难点和热点。智能材料的开发是目前防龋材料突破的新方向。传统pH敏感材料存在着合成设计复杂，作用不持久，难以在口内环境实现原位载药等问题。本项目针对当前pH敏感材料遇到的问题，以课题组前期合成的两种可聚合pH敏感型叔胺单体为核心，将其与复合树脂和粘接剂进行化学聚合反应，构建新型防龋智能材料。该新型防龋智能材料具有pH智能响应抗菌作用，通过非释放型和“质子化-去质子化”的可重复性实现口内原位载药；利用体外模型和动物模型全面评价材料生物安全性和防治龋病作用；并通过在不同pH环境中对牙菌斑生物膜的作用，探究其体外智能pH敏感机制；结合传统生物安全性检测和“口腔-肠道菌群”稳定全面评估新型防龋智能材料的生物安全性；进一步探索新型防龋智能材料的抗菌机制，筛选抗菌材料耐药菌和持留菌产生，为防龋智能材料的可持续发展奠定基础。

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