季铵盐磁性纳米载药复合体防治牙髓根尖周感染的研究

The removal of biofilm and infection control are the difficulties and hotspots in the prevention and treatment of dental pulp and periodontal disease. Developing new complex functional materials has been the new frontier in the related research. However, magnetic nanoparticle applications for the treatment of dental pulp and periapical disease have rarely been reported. Based on our previous studies, the complex of quaternary ammonium salts functionalized magnetic nanoparticles with metformin loaded was developed, with the combined properties of magnetic targeting, long-lasting antibacterial ability and anti-inflammatory effects. By using in vitro biofilm model, root canal infection model and animal model, the project aims to investigate the anti-biofilm effect of the complex on pulp and periapical related microbial infection, to explore the relationship between physical and chemical properties of materials and antimicrobial mechanisms, as well as the induction mechanism and removal strategies of potential drug resistant and persistent bacteria, to analyse the anti-inflammatory effect and mechanism of metformin in promoting the healing of periapical tissues. Collectively, all the efforts are expected to help comprehensively evaluate the application potentials of the complex in the prevention and treatment of dental pulp and periapical infection, and to provide a theoretical and experimental basis for the development of new complex functional materials.

控制感染和促进病变组织愈合是牙髓根尖周病防治的难点和热点。新型复合功能材料的研发是目前感染防治研究突破的新方向。磁性纳米颗粒具有磁靶向性，可作为载药系统，但在牙髓根尖周病防治领域的研究较少。本项目在课题组前期研究基础上，对磁性纳米颗粒进行季铵盐功能化修饰，负载抗炎药物二甲双胍，合成季铵盐磁性纳米载药复合体，利用体外生物膜模型、根管感染模型、动物模型，从磁性纳米颗粒磁靶向作用、季铵盐持久抗菌效果及载药分子二甲双胍的抗炎效能等角度，探讨磁性纳米颗粒与季铵盐功能化之间的相互作用，评价复合体材料对根管感染生物膜的抑制作用，探索材料的理化性能与抗菌机制之间的关系，以及耐药菌/持留菌产生机制和清除方法，探究二甲双胍在根尖周组织愈合过程中的抗炎作用及机制，全面评价该新型复合体材料在牙髓根尖周感染防治领域的应用潜能，为新型复合功能材料的研发提供一定的理论基础和实验依据。

控制感染和促进病变组织愈合是牙髓根尖周病防治的难点和热点。新型复合功能材料的研发是目前感染防治研究突破的新方向。课题组前期一直从事季铵盐抗菌材料相关的研究工作，本项目进一步证实牙本质粉末、牙本质基质和灭活菌存在时，对季铵盐抗菌单体有抑制作用。季铵盐DMADDM和DMAHDM对牙本质表面及小管内细菌有明显的抗菌作用。经30天饥饿处理后，戈登链球菌和粪肠球菌能对抗菌化合物产生耐药性，且对药效较强的药物能够更快建立耐药性。亚抑菌浓度DMADDM与DMAHDM能够抑制多菌种生物膜的生长，提高代谢水平、增强产酸能力。亚抑菌浓度条件下形成的生物膜对DMADDM和DMAHDM产生了耐药和交叉耐药。本项目还将2.5%DMADDM和1%磁性纳米粒子(MNP)对根管封闭剂EndoREZ进行抗菌改性，并未改变原有材料的细胞毒性、溶解性、根尖封闭性，并且能够在磁场作用下增加封闭剂的渗透率，体外对于粪肠球菌及多菌种生物膜均具有显著的抑制作用，通过构建动物根尖周感染模型，进一步证实改性材料可以有效促进根尖周组织愈合。另外，DMADDM和1%MNP改性修饰的根充糊剂EndoREZ，其孔隙率和孔隙量与iRoot SP差异不显著，但低于EndoREZ。在单尖充填技术中，改良根管封闭剂的穿透性、体内外长期抗菌性能和治疗效果均优于其他组。本项目已经发表相关论文7篇，5篇发表在SCI收录期刊，2篇为中文综述，另外尚有2篇在投稿当中。本项目的成果为新型复合功能材料的研发提供一定的理论基础和实验依据。