Biomimetic Growth of Enamel-like Hierarchical Structures

牙釉质层次结构的仿生生长

• 批准号: 8891403
• 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 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8891403
• 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; Health; 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 regeneration; 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; 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.

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.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和强大的初步数据提供了独特的见解，这些数据支持搪瓷再生的拟议仿生方法的可行性。尽管在促进口腔卫生和氟化方面做出了巨大努力，但仍需要进一步的研究来实现易于兴奋的，快速生长的搪瓷样生物陶瓷以进行仿生的修复。因此，迫切需要开发有效的方法来再生牙齿结构。中心假设是，可以通过调节矿物离子可用性，晶体生长动力学和晶体方向来恢复正确的牙釉质结构和功能。长期，更好地理解搪瓷矿物形成的机制将有助于开发新型的仿生和生物相容性的恢复材料，以用于牙釉质再生，例如，早期的龋齿治疗。氨基蛋白酶样材料，尤其是保留在商业合成的富含亮氨酸的氨基蛋白肽（LRAP）中的蛋白质蛋白的关键功能序列（LRAP）可能用于牙齿搪瓷结构和特性的再生。该提案的目标将通过完成以下两个具体目的来实现：目的1。确定LRAP和非磷酸化的全长氨基蛋白的机制和有效性，以指导使用焦磷酸盐（PPI）固化的超级磷酸盐磷酸盐磷酸盐溶液的体外结构的再生。酸蚀刻的人牙釉质的矿化动力学和外延生长将由PPI矿化抑制剂的水解调节1）搪瓷表面本身和2）碱性磷酸酶（AP）。目的2。确定高度过饱和磷酸钙溶液的机制和有效性，这些磷酸钙溶液通过使用AP稳定在磷酸化的天然和合成蛋白蛋白的稳定性上，以触发体外牙釉质结构的再生。全长天然（磷酸化的）猪amelogen蛋白和LRAP（+P）（磷酸钙溶液的有效稳定剂）将被研究为PPI的替代品，并还研究了其额外的潜力，以指导酸蚀刻的烯烃矿物质结构在添加的酸性矿物质结构上的再生。将使用SEM，EDX，FT-IR和放牧X射线衍射评估形成的矿物的程度，性质和方向。将评估基础线搪瓷特性的恢复和/或改善，以机械性能，物理化学特性和矿物质的强度进行评估。