MATRIX BASED MINERAL ENAMEL-BIOMIMETICS

基于基质的矿物釉质仿生学

• 批准号: 8597305
• 负责人: Janet M. Oldak
• 金额: $ 40.11万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8597305
• 关键词: Adhesions; Affect; Ameloblasts; Animal Model; Animals; Apatites; Architecture; Biocompatible Materials; Biological; Biomimetics; C-terminal; Carbonates; Cell Culture Techniques; Cell-Free System; Cells; Chemical Models; Chemicals; Chitosan; Clinical; Communities; Complex; Crystallization; Dental; Dental Enamel; Dental Materials; Dental caries; Dentistry; Development; Disease; Educational process of instructing; Enamel Formation; Engineering; Environmental Risk Factor; Esthetics; Event; Extracellular Matrix; Fracture; Future; Future Generations; Genes; Genetic; Goals; Growth; Hydrogels; Hydroxyapatites; In Situ; In Vitro; Knock-out; Learning; Lesion; Location; Mechanics; Mediating; Minerals; Molecular; Morphology; Natural regeneration; Oral; Oral cavity; Other Genetics; Outcome; Pattern; Peptide Hydrolases; Phase; Process; Property; Proteins; Proteolysis; Resistance; Resolution; Science; Scientist; Solid; Staging; Structure; Surface; Tissues; Transmission Electron Microscopy; amelogenin; base; biomineralization; bone; calcium phosphate; craniofacial; design; enamelin; improved; in vivo; interest; mineralization; nanorod; nanoscale; novel; particle; protein complex; protein structure; public health relevance; repaired; restoration; restorative material; self assembly; structural biology

DESCRIPTION (provided by applicant): This competing renewal continues to be based on the need for design and development of new biomaterials that will be utilized in repair of defective tooth enamel affected by genetic or environmental factors. We will focus on the study of fundamental chemical and biological principles of organic matrix assembly, disassembly, degradation, and control of mineral nucleation and growth in enamel biomineralization. We will continue developing biomimetic strategies for the synthesis of enamel-like material. We hypothesize that the highly organized carbonated hydroxyapatite crystals in enamel continuously grow by means of complex protein- protein, protein-proteinase, and protein-mineral interactions that are primarily controlled by the formation of a broad range of quaternary structures of amelogenin undergoing proteolytic possessing and interacting with non-amelogenins. We further hypothesize that functional enamel-like material can be prepared in a cell-free system by using a chitosan-amelogenin as the basic structural framework and incorporating principles that we have learned and are continuing to learn from our in vitro and in vivo studies. We propose: Aim I. To investigate amelogenin-enamelin interactions at a nanoscale level in vitro and in vivo. To study the dynamics of calcium phosphate mineralization events at a nanoscale level when enamelin is combined with amelogenin, using high resolution in situ atomic force (AFM) and in situ transmission electron microscopy (TEM). Aim II. To determine the amount of protein occluded inside synthetic crystals before and after C-terminal cleavage of amelogenin as well as in enamel crystals isolated from Mmp-20 knock-out animals. To investigate the dynamics of postnucleation mineralization events at a nanoscale level during Mmp-20 proteolysis of amelogenin, using high resolution in situ AFM and TEM. Aim III. To apply chitosan-based hydrogels as mineralization matrices in the development of biomimetic strategies for re-growth of a functional enamel-like material that could be used in the clinical setting to halt incipient carious lesions. Elucidating the dynamic interactions of enamelin and Mmp-20 with amelogenin proposed in aims I- II will contribute to our understanding of the structural biology and function of the enamel extracellular matrix in vivo, and will provide a soli ground for the design and development of improved dental materials (aim III). Moreover, this study will have a significant impact on the field of biomineralization, macromolecular self-assembly, protein structure, and the understanding of pathological enamel formation.

描述（由申请人提供）：这种竞争的更新继续基于设计和开发新生物材料的需求，这些新生物材料将用于修复受遗传或环境因素影响的有缺陷牙釉质。我们将重点研究有机基质组件的基本化学和生物学原理，拆卸，降解和控制矿物质生物矿化的矿物质成核和生长。我们将继续制定仿生策略来合成搪瓷样材料。我们假设，牙釉质中高度有组织的碳酸羟基磷灰石晶体通过复杂的蛋白质蛋白质，蛋白质 - 蛋白质酶和蛋白质矿物质相互作用不断生长，这些蛋白质蛋白质蛋白质酶和蛋白质 - 矿物质相互作用主要由蛋白质蛋白质蛋白质蛋白质的广泛蛋白质结构形成，这些蛋白质结构与蛋白质蛋白质相互作用众多蛋白质蛋白质相互作用，这些蛋白质结构多种多样，蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质的广泛和蛋白质相互作用。我们进一步假设，可以通过使用壳聚糖 - 淀粉蛋白酶作为基本结构框架来制备功能性牙釉质样材料，并纳入我们学到的原理，并继续从我们的体外和体内研究中学习。我们提出：目标I.在体外和体内研究纳米级水平上的氨基蛋白蛋白 - 云母相互作用。当使用高分辨率原位原子力（AFM）和原位透射电子显微镜（TEM）将搪瓷蛋白与氨基蛋白结合时，研究纳米级钙矿化事件的动力学。目标II。为了确定蛋白质内和之后的蛋白质的含量，在C末端裂解之前和之后，氨基蛋白酶以及从MMP-20敲除动物中分离出的搪瓷晶体中的蛋白质。使用高分辨率的原位AFM和TEM研究，在MMP-20蛋白水解过程中，在MMP-20蛋白水解期间，纳米级矿化事件的动力学在纳米级水平上的动力学。目标三。将基于壳聚糖的水凝胶应用于矿化矩阵，以开发仿生策略，以重新生长类似牙釉质样材料，可用于临床环境中，以阻止初期症状的病变。阐明搪瓷蛋白和MMP-20与目标I-II中提出的Amelogenin的动态相互作用将有助于我们对体内搪瓷细胞外基质的结构生物学和功能的理解，并将为改善牙科材料的设计和开发提供一个独源地（AIM III）。此外，这项研究将对生物矿化，大分子自组装，蛋白质结构以及对病理搪瓷形成的理解产生重大影响。