仿生肽引导纳米无定形磷酸钙定向有序再矿化牙体硬组织

The remineralization of the dental hard tissues is of great clinical value to the prevention and treatment of enamel/dentine caries，root caries and dentine hypersensitivity. With traditional methods using fluoride, the remineralization of teeth is carried out by formation of fluorapatite and through the epitaxial growth of the residual crystals. Due to the lack of ability of guiding the formation mineral crystals, the conventional methods cannot result in oriented and ordered remineralization of dental hard tissues, which are different from the natural ones. Although nano-amorphous calcium phosphate (nano-ACP), as precursor of hydroxyapatite (HAP), is the ideal choice for biomimetic remineralization, it is difficult for nano-ACP to accomplish self-assembly and bind to dental hard tissues. According to the biomimetic mineralization strategy from the non classical crystallization theory, we try to link a C-terminal peptide from amelogenin and the peptides that can specially bind to HAP or collagen with a proper linker, to obtain a biomimetic chimeric peptide including both guiding motif and binding motif to dental hard tissues, which can guide nano-ACP to remineralize enamel and dentine orderly. In this study, the biomimetic peptides would be optimized continuously through the in vivo and in vitro mineralization studies to obtain the shortest but the most functional chimeric peptide to induce ordered and oriented remineralization. This novel method would make the remineralized dental hard tissues approach natural healthy ones with respect to mechanical and structural properties. Additionally, the rationales of the design and mineralization of the biomimetic peptides would be clarified.

牙体硬组织再矿化对预防和治疗牙釉/本质龋、牙根面龋和牙本质过敏有重要临床价值。传统的氟化物再矿化方法只能凭借残余晶体的取向外延生长和形成氟磷灰石再矿化牙体硬组织，缺乏引导定向有序矿化的能力，形成矿物晶体的结构和排列与自然牙体硬组织不同。作为生物矿化过程中羟基磷灰石的前体: 纳米无定形磷酸钙是理想的再矿化材料，但缺乏定向有序排列自组装和与牙体硬组织特异性结合的能力。本研究利用基于非经典结晶理论的仿生矿化策略，将来源于釉原蛋白的C端多肽和能与羟基磷灰石或胶原特异性结合的多肽连接，得到具有引导功能端和牙体组织结合端的双功能仿生融合肽，用于引导纳米无定形磷酸钙定向有序再矿化脱矿牙釉/本质。本课题将通过体外和体内的矿化研究，不断优化仿生肽的设计，最终获得长度较小且能发挥定向有序矿化能力的仿生肽；使再矿化的牙体硬组织在机械力学性能和矿化结构上都达到或接近自然健康组织，并阐明仿生肽的设计和矿化作用规律。