聚合物稳定和诱导固态前驱相的仿生矿化机理研究

The bio-mineralization of the tooth hard tissues can stop the initial caries progress and promote the self-repairing of the dental lesions. The bio-mineralization is based on the polymer-induced liquid-precursor (PILP) process. However, the anticaries effect based on the PILP process is plausible in clinic due to the short-term interaction of biomineral materials by means of the mouthrinse or paste. Our preliminary research revealed the biomimetic mineralization of reconstituted type I collagen fibrils and the demineralized dentin using the polymer-induced solid precursor (PISP) process. The solid-precursor is amorphous calcium phosphate (solid ACP) stabilized by polymers such as non-collagen protein analogues. The self-etch adhesives or the film-forming materials hydroxypropylmethylcellulose (HPMC) loaded with solid ACP particles caused the remineralization of the inter- and intra-fibrils and the demineralized dentin in our pre-experimental study by means of the adhesion of the adhesives and the sol-gel property of HPMC. However, it is not clear how the polymer-stablized and -induced solid-precursors (solid ACP particles) in the self-etch adhesives and HPMC film migrated into the collagen fibrils in the wet condition and how solid-liquid-solid transformations occurred during the remineraliztion process. This study will investigate the biomimetic mineralization inspired by the polymer-stablized and -induced solid-precursor (solid ACP particles) process by using TEM, SEM, SAED and Micro-CT and explore the migration of Ca and P ions, and explore dissolution-reprecitation process and solid-liquid-solid phase transformation of the solid ACP particles in the wet condition by cryo-TEM, polarized light, FTIR, AFM, XRD and Raman spectrum. The bio-mineralization of the tooth hard tissues can stop the initial caries progress and promote the self-repairing of the dental lesions. The bio-mineralization is based on the polymer-induced liquid-precursor (PILP) process. However, the anticaries effect based on the PILP process is plausible in clinic due to the short-term interaction of biomineral materials by means of the mouthrinse or paste. Our preliminary research revealed the biomimetic mineralization of reconstituted type I collagen fibrils and the demineralized dentin using the polymer-induced solid precursor (PISP) process. The solid-precursor is amorphous calcium phosphate (solid ACP) stabilized by polymers such as non-collagen protein analogues. The self-etch adhesives or the film-forming materials hydroxypropylmethylcellulose (HPMC) loaded with solid ACP particles caused the remineralization of the inter- and intra-fibrils and the demineralized dentin in our pre-experimental study by means of the adhesion of the adhesives and the sol-gel property of HPMC. However, it is not clear how the polymer-stablized and -induced solid-precursors (solid ACP particles) in the self-etch adhesives and HPMC film migrated into the collagen fibrils in the wet condition and how solid-liquid-solid transformations occurred during the remineraliztion process. This study will investigate the biomimetic mineralization inspired by the polymer-stablized and -induced solid-precursor (solid ACP particles) process by using TEM, SEM, SAED and Micro-CT and explore the migration of Ca and P ions, and explore dissolution-reprecitation process and solid-liquid-solid phase transformation of the solid ACP particles in the wet condition by cryo-TEM, polarized light, FTIR, AFM, XRD and Raman spectrum.

聚合物诱导液态前驱相（PILP）的仿生矿化是矿化防龋的理论依据。矿化借助溶液或糊剂载体，在临床应用中无法发挥长期持久作用，导致矿化效果不确定。我们初步研究发现聚合物稳定和诱导固态前驱相（PISP）的仿生矿化，即聚合物稳定的固态无定形磷酸钙（ACP）添加到牙齿粘接剂或高分子成膜材料羟丙基甲基纤维素（HPMC）中，借助粘接剂或HPMC凝胶的粘性可较长时间粘附于牙面上，使重组I型胶原和脱矿牙本质矿化。在固化的牙齿粘接剂中或HPMC膜中的聚合物稳定的固态前驱相（ACP），如何在湿润条件进入胶原纤维内并实现钙磷迁徙和相转变均不清楚？拟用TEM//MicroCT等方法研究在牙齿粘接剂和HPMC 中的聚合物稳定和诱导固态ACP的仿生矿化效果，用cryo-TEM和偏正光镜等追踪牙齿粘接剂和HPMC膜中固态ACP在湿润环境下迁徙、溶解-再沉积和相变过程，为探索聚合物稳定和诱导固态前驱相的仿生矿化提供理论依据

基于聚合物诱导液态前驱相（PILP）的仿生矿化是矿化防龋的目前主要理论依据，为了解决借助溶液体系矿化牙齿在临床上应用有限的局限，我们通过聚合物稳定和诱导固态前驱相（PISP）的仿生矿化模式，将聚合物稳定的固态无定形磷酸钙（ACP）添加到牙齿粘接剂或高分子成膜材料羟丙基甲基纤维素（HPMC）中，借助粘接剂或HPMC凝胶的形式较长时间作用于牙面上，成功实现了对重组I型胶原、脱矿牙本质和牙釉质的矿化修复，并且在体内实验中得以验证其有效性。通过TEM/SEM验证负载了聚合物稳定和诱导固态ACP的矿化粘接剂和矿化贴膜的仿生矿化效果，通过MicroCT和纳米压痕表明了PISP矿化修复的牙齿的组织结构和机械性能得以恢复，用cryo-TEM观察矿化粘接剂和矿化贴膜中的固态ACP在唾液环境中溶解-再沉积和相变结晶为羟基磷灰石的过程，为探索聚合物稳定和诱导固态前驱相的仿生矿化和龋齿的再矿化修复提供全新策略和理论依据。我们还发现矿化粘接剂在矿化脱矿牙本质的同时，也可以对牙本质小管进行严密封闭和矿化，这也为牙本质敏感的临床治疗提供了新思路。通过在矿化粘接剂中添加荧光素，可以在临床上指示矿化粘接剂的矿化效果提供全新的策略。另外，通过对矿化贴膜的进一步优化改良，将掺氟ACP加入到矿化贴膜中，可以有效的预防釉质白斑，增强牙齿的抗酸防龋能力。矿化粘接剂和矿化贴膜也均表现出良好的生物相容性。综上所述，矿化粘接剂、矿化贴膜以及多种改良的形式，可以充分发挥龋病防治、白斑防治、牙齿脱敏等多重功效，为我们提供了全新的牙齿修复策略和思路，也为聚电解质稳定的固态前驱相在龋病防治中的应用和机制提供了理论基础。