交联剂对脱矿牙本质稳定及再矿化作用的机制研究

Dentin bonding degradation is still inevitable. How to prevent in advance (early remineralization of demineralized dentin) and to improve the treatment (enhance the durability of dentin resin bonding) are big challenges in clinical practice. Cross-linking agent application has been proposed an effective method to improve dentin bonding stability. However, much attention has been only paid to the enzymes and collagen cross-linking effect of the cross-linker itself in present studies. Whereas, the possible follow-up effect of the cross-linking agent has been ignored. Although natural crosslinking agent proanthocyanidin can improve dentin bonding durability, it has very weak ability to promote remineralization of the superficial layer in decalcified dentin. Based on our previous studies, we have found cross-linkers can not only inhibit the endogenous protease activity of dentin but also strengthen collagen anti-enzymatic properties. In this study, a single-layer recombinant type I collagen mineralization model is established to explore the nordihydroguaiaretic acid(NDGA)/carbodiimide(EDC) potential, as a proanthocyanidin biomimetic alternative for type I collagen whole assembly/mineralization process, demonstrate the safety applicable conditions for oral bio-environment and illustrate the synergistic mechanism of NDGA/EDC role in the demineralized dentin remineralization. This study will provide possible comprehensive solution for dentin bonding aging.

牙本质树脂粘接老化仍然不可避免。如何“早（Advance）”防（Prevention）——脱矿牙本质早期再矿化与“优（Improve）”治(Treatment)——改善牙本质粘接的耐久性，临床中亟待解决。交联剂对酶与胶原的交联作用可改善牙本质粘接老化，但研究中忽略了交联剂应用可能的后续效应。原花青素PA交联剂虽提高老化粘接强度，但PA仅有极弱的促脱矿牙本质再矿化能力，且局限于表浅层。项目组前期发现应用交联剂可以抑制内源性蛋白酶活性并增强胶原的抗酶解性能，提高粘接的稳定性，在此基础之上，我们拟构建单层重组I型胶原矿化模型、脱矿牙本质再矿化模型，探究去甲二氢愈创木酸NDGA、碳二亚胺EDC作为PA仿生替代物的可能性，建立具口腔生态环境安全性的适用条件，寻找NDGA/EDC促矿化的最直接证据，并阐明其对I型胶原、脱矿牙本质再矿化的促进或协同机制，为牙本质粘接老化早防与优治的综合解决方案提供思路。

交联剂对酶与胶原的交联作用可改善牙本质粘接老化，但研究中忽略了交联剂应用可能的后续效应。我们前期发现应用交联剂可以抑制内源性蛋白酶活性并增强胶原的抗酶解性能，提高粘接的稳定性，在此基础之上，我们拟探究了不同交联剂对于脱矿牙本质表面性能、降解特性、机械性征的影响，并联合使用仿生矿化液，探究交联剂对于脱矿牙本质再矿化的协同/促进作用。为牙本质粘接老化早防与优治的综合解决方案提供了思路。为探进一步究机制，进而构建单层重组I型胶原模型，并进一步扩大交联剂对于I型胶原基为主的细胞外基质（脱细胞小肠黏膜下层来源）的改性初步探索，为交联剂的后续生物应用提供了可能。