Engineering anti-fragile tooth/restorative interfaces

工程防脆牙齿/修复界面

• 批准号: 9152370
• 负责人: DAVID H. KOHN
• 金额: $ 26.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9152370
• 关键词: Acids; Address; Adhesions; Aldehydes; Amalgam; Amines; Apatites; Area; Binding; Biological Testing; Buffers; Charge; Chemicals; Collagen; Composite Resins; Defect; Dental; Dentin; Development; Enamel Formation; Engineering; Ensure; Esthetics; Exhibits; Failure; Filler; Geometry; Gingiva; Glass; Glass Ionomer Cements; Hybrids; Hydroxyapatites; Ketones; Ligaments; Longevity; Lysine; Measures; Mechanics; Mediating; Mercury; Modification; Oligopeptides; Particulate; Peptides; Phase; Powder dose form; Property; Research; Stimulus; Stress; Surface; System; Technology; Tendon structure; Testing; Time; Tissue Engineering; Tissues; Tooth Demineralization; Tooth structure; Toxic effect; Work; aqueous; base; biomaterial compatibility; bone; chemical bond; clinically significant; covalent bond; crosslink; demineralization; design; functional group; improved; innovation; interfacial; nanoparticle; particle; physical property; polymerization; primary outcome; repaired; response; restoration; restorative dentistry; restorative material; success; tooth surface

ABSTRACT Despite sufficiently high initial bond strengths exhibited by just about any contemporary dental restorative material, the tenacity of the bond can become progressively compromised over time. Reductions in bond strength are a result of mechanical and/or chemical insult degrading the substrate tissue, leading to bond fragility and, ultimately, restoration failure. This failure mechanism is particularly prevalent for class V restorations where the defect geometry both necessitates an enduring high bond strength to ensure longevity and results in persistent chemical insult owing to the proximity of the gingiva. To address this problem, we propose to engineer `anti-fragile' interfaces between composite dental restorative materials and the underlying tooth substrate. The clinical significance and innovative aspect of this research lies in the development of an adaptive interface through the use of engineered peptides that enable bond strengths to actually increase in response to insult. This enabling technology is expected to improve the longevity of class V dental restorations by having the restoration progressively bind with collagen exposed upon pH-mediated demineralization. The restorative materials will also bind to hydroxyapatite via a second set of peptides, thus they are affixed to both organic and inorganic phases of dentin. Inorganic, pH-buffering particles will be incorporated in the composite itself to mediate the local pH, delaying tissue loss owing to demineralization. Thus, we propose a dual materials-based approach to control the interface between a restoration and the tooth, ultimately increasing the longevity of the restoration. We will test the central hypothesis that incorporating tethering oligomers that bond to collagen and/or apatite on the tooth surface and functional groups on the composite resin will increase the bond strength over time and under acidic conditions. To test this central hypothesis, our specific aims and sub-hypotheses are to: 1. Develop oligomers bearing (i) dynamic covalent functional groups that, under reduced pH conditions, react with either the amine pendant groups of collagen-bound lysine residues or aldehyde and ketone groups resulting from post-translational lysine modification, and (ii) polymerizable pendant groups to covalently integrate dental restoratives with the substrate tissue. 2. Incorporate apatite-binding oligopeptides at the restoration/tissue interface to further improve restoration adhesion. 3. Synthesize self-buffering composites based on the incorporation of pH buffering inorganic nanoparticles that are able to act as localized pH buffers, mitigating chemical insult, and to test the biocompatibility of the materials systems developed in Aims 1-3. We will measure the interfacial bond strength, formation of marginal gaps, bulk physical properties and biocompatibility, with the primary outcome defining success being a bond strength superior to existing composites without peptide tethering, and biocompatibility equal to or superior to existing composites. In addition to the specific impact of the proposed work on restorative dentistry, our approach has much broader potential impact. The technologies proposed can be applied to any adhesion problem, including material- material, material-biologic, and biologic-biologic adhesion, and are therefore applicable to a wide variety of tissue engineering endeavors, including bone and dentin tissue engineering, tendon and ligament repair, and enamel formation.

抽象的 尽管几乎所有当代牙科修复体都表现出足够高的初始粘合强度 随着时间的推移，粘合的韧性会逐渐受到损害。债券减少 强度是机械和/或化学损伤降解基质组织的结果，导致粘合 脆弱性，最终导致修复失败。这种故障机制对于 V 类尤为普遍 缺陷几何形状都需要持久的高粘合强度以确保使用寿命的修复体 并由于靠近牙龈而导致持续的化学损伤。为了解决这个问题，我们 建议在复合牙科修复材料和底层之间设计“抗脆弱”界面 牙齿基质。本研究的临床意义和创新之处在于开发了一种 通过使用工程肽实现自适应界面，使键强度实际上增加 对侮辱的反应。这项技术有望提高 V 类牙齿修复体的使用寿命 通过使修复体逐渐与在 pH 介导的脱矿质作用下暴露的胶原蛋白结合。这 修复材料还将通过第二组肽与羟基磷灰石结合，因此它们固定在两者上 牙本质的有机相和无机相。无机 pH 缓冲颗粒将被纳入复合材料中 本身调节局部 pH 值，延缓因脱矿质导致的组织损失。因此，我们提出了双 基于材料的方法来控制修复体和牙齿之间的界面，最终增加 修复的寿命。 我们将测试中心假设，即结合与胶原蛋白和/或结合的束缚低聚物 牙齿表面的磷灰石和复合树脂上的官能团将增加粘结强度 时间和酸性条件下。为了检验这个中心假设，我们的具体目标和子假设是： 1. 开发带有 (i) 动态共价官能团的低聚物，在降低 pH 条件下， 与胶原蛋白结合的赖氨酸残基的胺侧基或醛和酮反应 由翻译后赖氨酸修饰产生的基团，和(ii)可聚合的侧基 将牙科修复材料与基底组织共价结合。 2. 在修复体/组织界面掺入磷灰石结合寡肽，进一步改善 修复粘连。 3. 基于pH缓冲无机纳米粒子合成自缓冲复合材料 能够充当局部 pH 缓冲剂，减轻化学损伤，并测试生物相容性 目标 1-3 中开发的材料系统。 我们将测量界面粘合强度、边缘间隙的形成、整体物理性能和 生物相容性，定义成功的主要结果是优于现有的粘合强度 复合材料没有肽束缚，生物相容性等于或优于现有复合材料。在 除了拟议工作对修复性牙科的具体影响外，我们的方法还具有更广泛的影响 潜在的影响。所提出的技术可以应用于任何粘合问题，包括材料- 材料、材料-生物和生物-生物粘附，因此适用于各种 组织工程工作，包括骨和牙本质组织工程、肌腱和韧带修复，以及 牙釉质的形成。