A Peptide-Based Biomineralization Strategy for Tooth Repair

基于肽的牙齿修复生物矿化策略

• 批准号: 10328496
• 负责人: Janet M. Oldak
• 金额: $ 38.8万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10328496
• 关键词: Adhesions; Apatites; Biocompatible Materials; Biomimetic Materials; Biomimetics; Cervical; Chemicals; Chitosan; Clinical; Collagen; Crystallization; Custom; Dental; Dental Enamel; Dental caries; Dental crowns; Dentin; Dentin Sensitivity; Development; Enamel Formation; Ensure; Experimental Models; Formulation; Goals; Growth; Human; Hydrogels; Hypersensitivity; In Situ; In Vitro; Lead; Legal patent; Lesion; Longevity; Minerals; Modeling; Oral cavity; Outcome; Pathway interactions; Peptides; Phosphorus 32; Plant Roots; Prevalence; Prevention; Raman Spectrum Analysis; Regimen; Reporting; Root Caries; Slice; Structure; Surface; Technology; Temperature; Thick; Tooth structure; aging population; amelogenin; base; biomineralization; calcium phosphate; chemical binding; clinical application; crystallinity; demineralization; dental structure; efficacy evaluation; healing; improved; mechanical properties; mineralization; novel; prevent; rational design; remineralization; repaired; restoration; restorative material; tissue reconstruction; treatment strategy

PROJECT SUMMARY / ABSTRACT We seek to develop a biomineralization approach to grow a biomimetic enamel-like layer that will have a seamless chemical attachment to natural enamel and dentin. Such a structured biomaterial will prevent progression of tooth decay and will be utilized as an enhanced dental restorative material for treating non- carious cervical lesions (NCCL). We reported that our patent-pending hydrogels composed of chitosan and amelogenin (CS-AMEL) can promote regrowth of an enamel-like layer and remineralize dentin. Here, we will utilize an amelogenin-inspired peptide-based biomimetic strategy. The advantage of using peptides for translational/clinical purposes lies in the fact that short peptides are easier to use as well as more economical and practical for clinical application. The pathway to regulatory approval may also be easier for peptides. We hypothesize that our rationally designed peptide chitosan hydrogel (Amel-P-CS) will stimulate growth of an enamel-like mineralized layer at the dentin/enamel interface and will promote guided remineralization of the dentin collagen compartments, thereby enhancing bonding to the organic content in dentin. Following specific aims are proposed: Aim I) To investigate the assembly and apatite mineral-forming potential of amelogenin- derived peptides P26 and P32 prior to their application in the chitosan hydrogel. We will use CD, Cryo-TEM, micro Raman spectroscopy and in situ AFM to investigate the peptides’ secondary and tertiary structures and their influence on apatite mineralization in the presence and absence of collagen in vitro. Aim II) To develop and optimize the formulation of P26 and P32 peptide-containing chitosan hydrogels (Amel-P-CS) and examine the potential of Amel-P-CS hydrogels to rebuild an enamel-like layer with enhanced mechanical properties and robust attachment to etched enamel surface. Human molar crown slices with demineralized enamel surfaces will be used. Aim III) To examine the potential of Amel-P-CS hydrogels to rebuild an enamel-like layer with enhanced mechanical properties and robust attachment to a demineralized dentin surface. We will further examine the potential of the hydrogels to nucleate and grow apatitic crystals within the dentin collagen compartments, thereby enhancing bonding to the organic content in dentin. Human molar crown slices with demineralized dentin surfaces will be used. Aim IV) To examine the efficacy of Amel-P-CS hydrogels in repairing artificial cervical lesions in ex vivo models where enamel and dentin are exposed. We will use whole extracted teeth subjected to a pH-cycling regimen. In summary: If the goals of proposed aims are achieved, we will deliver a technology (hydrogel delivered on dental trays) that: a) will provide enhanced biomimetic enamel-like coating material, b) effectively rebuild dental structures lost due to NCCL lesions, and c) will prevent dentinal hypersensitivity and progression of tooth decay.

项目摘要 /摘要 我们试图开发一种生物矿化方法来生长仿生搪瓷样层，该层将具有 无缝的化学物质附着于天然搪瓷和牙本质。这样的结构化生物材料将阻止 蛀牙的进展，将被用作增强的牙科修复材料，用于治疗非 - 龋齿宫颈病变（NCCL）。我们报告说，我们的未申请专利水凝胶由壳聚糖和 氨基蛋白蛋白（CS-Amel）可以促进类似搪瓷层的遗憾，并提醒牙本质。在这里，我们会的 利用基于氨基蛋白蛋白启发的肽基于肽的仿生策略。使用Petides进行的优势 翻译/临床目的在于一个事实，即短肽更易于使用，并且更经济 并且可用于临床应用。对于Petides来说，进行监管批准的途径也可能更容易。我们 假设我们理性设计的肽壳聚糖水凝胶（Amel-P-CS）将刺激生长 牙本质/搪瓷界面处的搪瓷样矿物质层，将促进指导的提醒 牙本质胶原蛋白室，从而增强了与牙本质有机含量的键合。以下特定 提出了目的：目标i）研究氨基蛋白素的组装和磷灰石矿物质形成潜力 在壳聚糖水凝胶中施用之前，衍生的肽P26和P32。我们将使用CD，Cryo-Tem， 微拉曼光谱和原位AFM，以研究娇小的次级和第三纪结构以及 在体外胶原蛋白的存在和不存在的情况下，它们对磷灰石矿化的影响。目标ii）发展 并优化P26和P32含胡椒的壳聚糖水凝胶（AMEL-P-CS）的配方 Amel-P-CS水凝胶具有增强的机械性能和 与蚀刻的搪瓷表面的牢固附着。人类摩尔冠状切片，具有解矿化的搪瓷表面 将使用。目标iii）检查Amel-P-CS水凝胶的潜力，以重建与牙釉质样层 增强的机械性能和对债务牙本质表面的稳健附件。我们将进一步 检查水凝胶对核并在牙本质胶原蛋白内生长凋亡晶体的潜力 隔室，从而增强与牙本质有机含量的键合。人类摩尔冠切片 将使用去矿化的牙本质表面。 AIM IV）检查AMEL-P-CS水凝胶的效率 在暴露于搪瓷和牙本质的离体模型中修复人工宫颈病变。我们将全部使用 提取牙齿受到pH循环方案。总而言之：如果实现了拟议的目标的目标， 我们将提供一项技术（在牙科托盘上交付的水凝胶）：a）将提供增强的仿生剂 类似搪瓷的涂层材料，b）有效地重建由于NCCL病变而失去的牙齿结构，c）将 防止牙齿衰减的牙齿过敏和进展。