负载仿生矿化前驱体的大孔介孔硅PA-ACP@AF-eMSN预处理剂在牙本质仿生矿化中的应用研究

Amorphous calcium phosphate (ACP) as precursors of biomineralization of bone and teeth has been confirmed. ACP infiltrate into the collagen through the gap zone to mineralize the collagen. Biomimetic remineralizaiton of the collagen is the ultimate solution for increasing the bonding strength and enhance the bonding durability of resin-dentin bonds. It is hard for the polymer induced liquid precursor biomineralizaition system to have practicle application. So, a pathway to push the polymer induced liquid precursor biomineralizaition system transform from concept into application is urgent..In our previous study, expanded-pore mesoporous silica nano particles (AF-eMSN) has been proved to be an excellent choice for loading polymer-stabilized ACP (PA-ACP). The solution based biomineralization concept could be translated via the use of eMSN into a carrier-based delivery system to store and release polymerstabilized ACP precursors for biomineralization of collagen fibrils. Hence, in this study, we try to use the delivery system PA-ACP@AF-eMSN as a dentin pre-conditioner, to investigate the remineralization of type I collagen sponge, to explore the remineralization ability of the pretreatment agent while applied on the hypomineralized dentin surface directly, to test the influence on the mechanical property and durability of the resin-dentin bonds and confirm the biocompatibility of this material. Finally, the conclusion that whether PA-ACP@AF-eMSN could be used as a pretreatment agent with good biomineralization ability and the best pretreatment agent concentration were concluded..This research is the first application of translation of solution-based biomineralization, which will help us further explore dental and medical material with bioactivity.

无定型磷酸钙仿生矿化前驱体在骨和牙齿矿化中,能渗透入I型胶原纤维内部进行胶原再矿化。这种仿生再矿化在树脂-牙本质粘接体系中是增加粘接强度和粘接耐久性的终极措施。但目前液体介导的仿生矿化系统难以应用于实际，因此，我们急需寻找一个途径将液体介导的仿生矿化理论向应用转化。此前，我们已经合成能负载仿生矿化前驱体（PA-ACP）的大孔介孔硅（AF-eMSN），通过此纳米颗粒传输系统，储存、释放PA-ACP并成功矿化胶原纤维。 在本研究中，我们试图使用PA-ACP@AF-eMSN作为牙本质粘接中的预处理剂，检测其再矿化3D胶原海绵的能力，探索其应用于脱矿牙本质后再矿化牙本质胶原纤维的能力，明确其对树脂-牙本质粘接性能的影响，检验其生物相容性。最终综合各种因素，确定PA-ACP@AF-eMSN是否能作为牙本质仿生矿化的有效预处理剂及确定其适宜浓度。这是液体仿生矿化理念向实践应用转化的首次探索。

龋病不仅发病率高、治疗费用高，并且龋病充填治疗后易发生继发龋、边缘微渗漏等粘接失败的问题。因此，提高树脂-牙本质粘接的耐久性是一个亟待解决的问题。在脱矿的骨和牙齿矿化中，无定形磷酸钙仿生矿化前驱体能渗透入I型胶原纤维内部进行胶原纤维再矿化。这种仿生再矿化在树脂-牙本质粘接体系中是增加粘接强度和粘接耐久性的终极措施。但是目前液体介导的仿生矿化体系难以应用于实际，因此，选用有效的转运载体，将仿生矿化前驱体（PA-ACP）转运至需要仿生矿化的区域成为理论向应用转化的难点。.本课题通过完成四方面的内容：.一. 研究PA-ACP@AF-eMSN 颗粒溶液对人工脱矿牙本质模型的仿生再矿化。.二. 研究PA-ACP@AF-eMSN 作为预处理剂时对牙本质仿生再矿化的影响。.三. 研究PA-ACP@AF-eMSN 预处理剂对全酸蚀粘接系统树脂-牙本质粘接性能的影响。.四. 检测不同浓度 PA-ACP@AF-eMSN 预处理剂对人牙髓干细胞增殖的影响，以评价其生物相容性。.证实：一. PA-ACP@AF-eMSN颗粒溶液具有仿生再矿化能力，仿生再矿化能从2D胶原纤维再矿化模型向3D人工脱矿牙本质再矿化模型外延。.二. PA-ACP@AF-eMSN颗粒作为预处理剂，能在不额外添加外界钙磷来源时获得对脱矿牙本质的有效仿生再矿化。.三. PA-ACP@AF-eMSN颗粒作为预处理剂的最适浓度为5mg/ml，在此浓度上能取得兼顾仿生再矿化、粘接效能的最优结果。这一适宜浓度的PA-ACP@AF-eMSN 预处理剂能增加牙本质-树脂粘接界面粘接强度，增加粘接耐久性。.四. PA-ACP@AF-eMSN对人牙髓干细胞具有较好的生物相容性。. 综上，仿生矿化前驱体PA-ACP能稳定地储存于AF-eMSN，形成PA-ACP@AF-eMSN转运系统，其直接应用于牙本质脱矿区域，能获得脱矿胶原纤维的有效原位仿生再矿化。PA-ACP@AF-eMSN能作为牙本质全酸蚀粘接系统中兼具仿生再矿化混合层胶原纤维、增强粘接性能双重功能的预处理剂。这是将由液体介导的仿生再矿化理念应用到以纳米颗粒为载体介导的首创，这种从理论到临床实践的转化，开拓了仿生再矿化的新途径，大大增加了仿生再矿化在医学领域应用的可行性。