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.

项目概要/摘要 我们寻求开发一种生物矿化方法来生长仿生牙釉质层，该层将具有 与天然牙釉质和牙本质的无缝化学附着将防止这种结构化生物材料的发生。 蛀牙的进展，将被用作增强牙齿修复材料，用于治疗非 我们报道了我们正在申请专利的水凝胶由壳聚糖和 釉原蛋白 (CS-AMEL) 可以促进牙釉质层的再生，并使牙本质再矿化。 利用基于牙釉蛋白的肽仿生策略使用肽的优势。 翻译/临床目的在于短肽更易于使用且更经济 对于临床应用来说，监管批准的途径也可能更容易。 我们合理设计的肽壳聚糖水凝胶 (Amel-P-CS) 将刺激生长 牙本质/牙釉质界面处的牙釉质样矿化层，将促进牙本质的引导再矿化 牙本质胶原蛋白隔室，增强与牙本质有机成分的结合。 提出了目标： 目标 I) 研究釉原蛋白的组装和磷灰石矿物形成潜力 衍生肽 P26 和 P32 在应用于壳聚糖水凝胶之前我们将使用 CD、Cryo-TEM、 显微拉曼光谱和原位原子力显微镜研究肽的二级和三级结构 在体外存在和不存在胶原蛋白的情况下它们对磷灰石矿化的影响目标 II) 开发。 优化含P26和P32肽壳聚糖水凝胶（Amel-P-CS）的配方并检验 Amel-P-CS 水凝胶重建具有增强机械性能的牙釉质层的潜力 与蚀刻牙釉质表面牢固附着，具有脱矿牙釉质表面。 目标 III) 检查 Amel-P-CS 水凝胶重建牙釉质层的潜力。 我们将进一步增强机械性能和与脱矿牙本质表面的牢固附着。 检查水凝胶在牙本质胶原蛋白内成核和生长磷灰石晶体的潜力 隔室，从而增强与牙本质中有机物的结合。 将使用脱矿质牙本质表面。目标 IV) 检查 Amel-P-CS 水凝胶在治疗中的功效。 在牙釉质和牙本质暴露的离体模型中修复人工宫颈病变，我们将使用整个。 拔除的牙齿接受 pH 循环方案 总之：如果实现了所提出的目标， 我们将提供一种技术（在牙托上提供水凝胶）：a）将提供增强的仿生性 牙釉质涂层材料，b) 有效重建因 NCCL 病变而丢失的牙齿结构，c) 将 预防牙本质过敏和蛀牙的进展。