牙结石细菌启迪的牙体硬组织原位修复材料的设计与应用

Although existing biomimetic materials have been widely studied for dental remineralization to restore dental tissue, these materials commonly have weak bonding with dentine, poor biomimetic mineralization ability and/or high possibility to be eroded by secondary caries. Dental calculus, composed primarily of hydroxyapatite, has strong bonding with the tooth surface. Dental calculus is formed fast on the tooth surface. It shows good adhesion and long-term stability. The presence of bacteria, one of the main reasons causes dental calculus, especially the Streptococcus mitis (S. mitis) which has strong interaction with dental tissue. In this project, inspired by the functions of S. mitis, the applicator plans to design a series of dental restorative materials, ‘artificial bacteria’, which have similar structure as S. mitis. The ‘artificial bacteria’ has a hydrophilic outer layer, a hydrophobic middle layer and a soft core. The shell, consists of the outer and middle layer, formed by amphiphilic block poly(α-amino acid). The core formed by hyaluronic acid nanogel. Additionally, the ‘artificial bacteria’ will link different chemical groups via chemical reaction, such as galactose, or load antibacterial drugs, such as triclosan. The abilities of ‘artificial bacteria’ of adsorption/repair/anti-bacteria for dental tissue will be studied. The innovation points of this project include: 1) the design of biomimetic materials with the structure similar as S. mitis, 2) the synthesis of novel materials with adsorption/repair/anti-bacterial abilities for dental tissue. This project is promised to provide novel biomaterials and theories for dental restoratives.

仿生材料用于促牙体硬组织再矿化进而修复受损牙体已有很多研究，但此类材料与牙体硬组织间的界面结合力较弱、促再矿化效果不佳且/或易受口腔细菌的侵蚀，限制了材料的临床发展。然而，牙结石，主要成分是羟基磷灰石，却能在牙体表面快速形成、牢固粘附并稳定存在。受牙结石形成过程中细菌的功能启发，通过剖析与牙面具有强结合力的轻型链球菌，申请人拟设计仿该细菌结构的牙体硬组织修复材料——透明质酸纳米凝胶接枝两亲性两嵌段聚氨基酸形成的、具有核壳结构的“人工细菌”。进一步向“人工细菌”中引入半乳糖等轻型链球菌的特异性吸附基团，并装载抗菌药物。最后研究“人工细菌”对牙体硬组织的原位吸附/修复/抗菌能力。本项目的创新点在于：设计制备受轻型链球菌结构和功能启发的仿生牙体硬组织修复材料，实现对牙体硬组织的强吸附、高效修复和长效抗菌。本项目有望提供有临床应用前景的新型牙体硬组织修复材料，并为此类材料的设计提供新思路。

牙体硬组织损伤如龋病已经成为了威胁国民身心健康的主要疾病之一，对国家和社会带来了沉重的经济负担。在项目的支持下，为解决牙体硬组织修复材料常常受限于材料-硬组织界面作用力较弱、促再矿化效果不佳且易受细菌影响修复效果的影响，导致材料的原位修复能力较差的问题，本研究受牙结石细菌可以牢固粘附在硬组织表面并诱导原位矿化形成牙结石的特点所启发，刨析细菌结构-功能的相互关系，设计制备了一系列仿牙结石细菌结构的材料，并研究其对羟基磷灰石/牙体硬组织的吸附能力、抗菌能力和诱导原位再矿化的能力。研究结果明确了仿细菌菌毛结构的酸性长链接枝中性分子的PASP-PEG具有对牙体硬组织的强吸附能力、抗细菌粘附能力和诱导原位在再矿化能力，协同以上功能原位修复牙体硬组织；仿细菌整体结构的纳米内核接枝中性疏水短链/酸性亲水长链可以有效吸附多种界面，且对牙体硬组织的主要成分羟基磷灰石具有特异性的强吸附；仿牙本质衍生基质囊泡结构的血小板囊泡可以有效交联牙本质胶原纤维并促进牙本质表面和牙本质小管内的原位再矿化。该研究构建了高效牙体硬组织原位修复的仿生材料，实现材料的安全性和模块化应用，为临床提供了具有应用前景的新型牙体硬组织修复材料，并为此类材料的设计提供了理论依据。