基于矿化前驱体-甲基化EGCG的牙本质多功能生物屏障的构建及其应用研究

Enamel is a natural barrier to protect the internal tooth tissue such as dentin. Owing to the presence of dentinal tubules and lower mineralization degree than enamel, the exposure of dentin after the loss of enamel often leads to the occurrence of dentin hypersensitivity and caries. Therefore, it is of great significance to realize effective protection after dentin exposure to fight with dentin hypersensitivity and caries. Our project intends to fabricate pore-expanded mesoporous silica nanoparticles (peMSN) as nano-carrier, and utilize poly (allylamine) hydrochloride stabilized amorphous calcium phosphate (PAH-ACP) and epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) as mineralizing precursors and antibacterial agent, respectively, to synthesize a sort of PAH-ACP and EGCG3''Me-based delivery system (EGCG3''Me@PAH-ACP@peMSN). After the application of this system on exposed dentin, it can sustainably occlude the dentinal tubules and tightly integrate with dentinal matrix, to establish a kind of versatile bio-barrier to isolate external stimulus and invasion towards dentin. The bio-barrier holds the ability not only to release PAH-ACP to promote collagen remineralization but also to release EGCG3''Me to inhibit Streptococcus mutans biofilm formation, thus realizing effective protection for exposed dentin, and developing theoretical basis and new strategy for comprehensive settlement for dentin hypersensitivity and caries.

牙釉质是保护牙本质等内层组织的天然屏障。当牙釉质丧失后，由于牙本质小管的存在及矿化程度较牙釉质低等特点，易导致牙本质敏感和龋的发生。如何有效保护暴露的牙本质从而抵御敏感和龋的侵害具有重要临床意义。本课题拟制备扩孔介孔硅(peMSN)作为纳米载体，利用聚烯丙胺稳定的无定形磷酸钙(PAH-ACP)和甲基化EGCG(EGCG3''Me)分别作为矿化前驱体和抗菌药物，合成一种基于PAH-ACP和EGCG3''Me的转运体系(EGCG3''Me@PAH-ACP@peMSN)。该体系应用于暴露的牙本质后，可持久稳定地封闭牙本质小管并与牙本质基质紧密结合，进而构建一种多功能生物屏障以隔绝外界对牙本质的刺激与侵袭：一方面缓释PAH-ACP促进牙本质胶原再矿化，另一方面缓释EGCG3''Me抑制变形链球菌生物膜形成，最终实现对暴露牙本质的有效保护，有望为牙本质敏感和龋病问题的综合解决提供理论基础和新的策略。

牙釉质是保护牙本质等内层组织的天然屏障。当牙釉质丧失后，由于牙本质小管的存在及矿化程度较牙釉质低等特点，易导致牙本质敏感和龋的发生。如何有效保护暴露的牙本质从而抵御敏感和龋的侵害具有重要临床意义。为综合解决这一问题，本课题创新性地提出了一种牙本质多功能生物屏障的理念，通过将目前牙科领域的研究前沿包括纳米载体、仿生矿化和天然抗菌的巧妙整合来实现。主要实施策略是利用理化性质稳定的中空介孔硅(HMS)作为纳米载体，利用聚烯丙胺稳定的无定形磷酸钙(PAH-ACP)和表没食子儿茶素没食子酸酯(EGCG)分别作为矿化前驱体和天然茶多酚抗菌药物，设计合成了一种基于PAH-ACP和EGCG的新型转运体系EGCG/PAH-ACP@HMS(E/PA@HMS)。该体系能够持久稳定地封闭牙本质小管、实现牙本质胶原纤维内矿化和脱矿牙本质再矿化、抑制牙本质表面致龋细菌生物膜形成，从而构建一种多功能生物屏障隔绝外界刺激实现对暴露牙本质的有效保护。这种新策略同时完成了小管封闭、胶原矿化、抑制生物膜三重任务，有望为牙本质敏感和龋病两方面问题解决开辟新的方向、具有较大的临床推广和转化价值。此外，本课题还研究了应用基于介孔硅的不同纳米转运体系(EGCG@nHAp@MSN)对提高牙本质粘接性能和预防牙本质敏感及继发龋的影响，从不同层面探讨了对牙本质进行功能化改性的新路径，为牙本质粘接长期持久性不足问题的解决提供理论依据。