Biomimetic Growth of Enamel-like Hierarchical Structures

牙釉质层次结构的仿生生长

• 批准号: 8702502
• 负责人: Seo-Young Kwak
• 金额: $ 14.78万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702502
• 关键词: Acids; Address; Adhesives; Alkaline Phosphatase; Amelogenesis Imperfecta; Area; Biocompatible; Biomimetic Materials; Biomimetics; Child; Data; Dental Enamel; Dental Hygiene; Dental Research; Dental caries; Dentin; Development; Diphosphates; Drug Formulations; Early treatment; Effectiveness; Enamel Formation; Excision; Exhibits; Extracellular Matrix Proteins; Family suidae; Future; Goals; Growth; Hardness; Human; Hydrolysis; Hydroxyapatites; In Situ; In Vitro; Incidence; Investigation; Ions; Kinetics; Laboratories; Length; Lesion; Mechanics; Methods; Minerals; Nanostructures; Natural regeneration; Nature; Needles; Outcome; Property; Protein Dephosphorylation; Recombinants; Regulation; Research; Research Design; Resistance; Solutions; Structure; Surface; Testing; Tissues; Tooth structure; Water fluoridation; Work; X ray diffraction analysis; X-Ray Diffraction; amelogenin; base; calcium phosphate; chemical property; demineralization; design; enamel matrix proteins; fluorosis; improved; in vivo; inhibitor/antagonist; inorganic phosphate; insight; leucine-rich amelogenin peptide; mineralization; nano; nanoparticle; nanostructured; novel; peptide P; prevent; public health relevance; repaired; research study; restoration; restorative material; tissue regeneration

DESCRIPTION (provided by applicant): The proposed study is designed to prove that highly oriented enamel-like nano- and micro-structures of acid-etched human enamel can be generated using pyrophosphate (PPi)-stabilized highly supersaturated solutions in the presence of specific molecules that exhibit the capacity to guide the epitaxial growth of mature enamel crystals. This study is guided by recent advances in the PI's laboratory that have provided unique insight into the mechanism by which enamel matrix proteins regulate enamel formation and strong preliminary data that support the feasibility of proposed biomimetic approaches for enamel regeneration. Despite tremendous efforts in promoting oral hygiene and fluoridation, further research is needed to achieve an easy-to-apply, fast growing enamel-like bioceramic for biomimetic repair. Thus, there is a great need to develop effective means to regenerate tooth structures. The central hypothesis is that the restoration of proper enamel structure and function can be achieved through the regulation of mineral ion availability, crystal growth kinetics, and crystal orientation. Long-term, a better understanding of the mechanism of enamel mineral formation will aid in the development of novel biomimetic and biocompatible restorative materials for enamel regeneration and, for example, the treatment of early dental caries. Amelogenin-like materials, especially key functional sequences of amelogenin retained within commercially synthesized leucine-rich amelogenin peptide (LRAP) can potentially be used in the regeneration of tooth enamel structure and properties. The goals of this proposal will be achieved through the completion of the following two Specific Aims: Aim 1. To determine the mechanism and effectiveness of LRAP and non-phosphorylated full-length amelogenin to guide the regeneration of enamel structure in vitro using pyrophosphate (PPi)-stabilized supersaturated calcium phosphate solutions. Mineralization kinetics and epitaxial growth of acid-etched human enamel will be regulated by the hydrolysis of the PPi mineralization inhibitor by 1) the enamel surface itself and 2) alkaline phosphatase (AP). Aim 2. To determine the mechanism and effectiveness of highly supersaturated calcium phosphate solutions that are stabilized by phosphorylated native and synthetic amelogenins using AP to trigger the regeneration of the enamel structure in vitro. Full-length native (phosphorylated) porcine amelogenin and LRAP(+P), potent stabilizers of supersaturated calcium phosphate solutions, will be studied as substitutes for PPi and examined also for their additional potential to guide th regeneration of the acid-etched enamel mineral structure upon dephosphorylation by added AP. The extent, nature, and orientation of formed mineral will be assessed using SEM, EDX, FT-IR and grazing incidence X-ray diffraction. The restoration and/or improvement of base-line enamel properties will be assessed with respect to mechanical properties, physico- chemical properties, and strength of mineral attachment.

描述（由申请人提供）：拟议的研究旨在证明，在特定的存在下，使用焦磷酸盐（PPi）稳定的高度过饱和溶液可以生成酸蚀人类牙釉质的高度定向的牙釉质纳米和微米结构。具有引导成熟牙釉质晶体外延生长能力的分子。这项研究以 PI 实验室的最新进展为指导，这些进展为牙釉质基质蛋白调节牙釉质形成的机制提供了独特的见解，并提供了强有力的初步数据，支持所提出的牙釉质再生仿生方法的可行性。尽管在促进口腔卫生和氟化方面付出了巨大努力，但仍需要进一步研究来实现一种易于使用、快速生长的牙釉质样生物陶瓷，用于仿生修复。因此，非常需要开发有效的方法来再生牙齿结构。中心假设是，可以通过调节矿物质离子的可用性、晶体生长动力学和晶体取向来恢复适当的牙釉质结构和功能。从长远来看，更好地了解牙釉质矿物质形成机制将有助于开发用于牙釉质再生的新型仿生和生物相容性修复材料，例如治疗早期龋齿。牙釉蛋白样材料，尤其是商业合成的富含亮氨酸的牙釉蛋白肽（LRAP）中保留的牙釉蛋白关键功能序列，可潜在用于牙釉质结构和特性的再生。本提案的目标将通过完成以下两个具体目标来实现： 目标 1. 确定 LRAP 和非磷酸化全长牙釉蛋白在体外使用焦磷酸盐（PPi）指导牙釉质结构再生的机制和有效性)-稳定的过饱和磷酸钙溶液。酸蚀人类牙釉质的矿化动力学和外延生长将受到 PPi 矿化抑制剂水解的调节，水解作用是 1) 牙釉质表面本身和 2) 碱性磷酸酶 (AP)。目标 2. 确定高度过饱和磷酸钙溶液的机制和有效性，该溶液由磷酸化的天然和合成牙釉蛋白稳定，使用 AP 触发牙釉质结构体外再生。全长天然（磷酸化）猪牙釉蛋白和 LRAP(+P) 是过饱和磷酸钙溶液的有效稳定剂，将作为 PPi 的替代品进行研究，并检查它们指导酸蚀牙釉质矿物结构再生的额外潜力添加AP后去磷酸化。形成矿物的范围、性质和方向将使用 SEM、EDX、FT-IR 和掠入射 X 射线衍射进行评估。将根据机械性能、物理化学性能和矿物质附着强度来评估基线牙釉质性能的恢复和/或改善。