Engineering anti-fragile tooth/restorative interfaces

工程防脆牙齿/修复界面

• 批准号: 9754109
• 负责人: DAVID H. KOHN
• 金额: $ 27.82万
• 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/9754109
• 关键词: Acids; Address; Adhesions; Aldehydes; Amalgam; Amines; Apatites; Area; Binding; Biocompatible Materials; Biocompatible Materials Testing; Biological; 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; Polymers; 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; mechanical properties; 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效率都表现出足够高的初始纽带强度 材料，随着时间的推移，债券的坚韧性可能会逐渐受到损害。减少键 强度是机械和/或化学侮辱降解底物组织的结果，导致键 脆弱性，最终是恢复失败。这种失败机制对于V类特别普遍 缺陷几何形状都需要持久的高粘结强度以确保寿命 由于牙龈的接近性，导致持续的化学侮辱。为了解决这个问题，我们 建议在复合牙科修复材料和基础之间设计“反碎片”接口 牙齿底物。这项研究的临床意义和创新方面在于发展 通过使用工程肽的自适应界面，使粘结强度实际上增加 对侮辱的反应。预计这种促成技术将改善V级牙科修复体的寿命 通过使恢复与pH介导的脱矿化后暴露的胶原蛋白逐渐结合。这 恢复材料还将通过第二组肽结合与羟基磷灰石，因此它们都粘在两者中 牙本质的有机和无机阶段。无机，pH缓冲颗粒将纳入复合材料 本身可以介导局部pH，从而延迟了由于脱矿化而延迟组织损失。因此，我们提出了双重 基于材料的方法来控制修复和牙齿之间的接口，最终增加 恢复的寿命。 我们将测试中心假设，即结合了与胶原蛋白和/或粘合的束缚低聚物 牙齿表面上的磷灰石和复合树脂上的官能团将提高键强度 时间和在酸性条件下。为了检验这一中心假设，我们的具体目的和亚类型是： 1。开发轴承（i）动态共价官能团，在降低的pH条件下， 与胶原结合赖氨酸残基的胺吊坠或醛和酮反应 翻译后赖氨酸修饰产生的组，以及（ii）可聚合的吊坠组 共价将牙齿恢复与底物组织整合。 2。在修复/组织界面上掺入磷灰石结合寡肽以进一步改进 恢复粘附。 3。基于pH缓冲无机纳米颗粒的融合而综合自我缓冲复合材料 能够充当局部pH缓冲液，减轻化学侮辱，并测试 AIMS 1-3中开发的材料系统。 我们将衡量界面键强度，边缘间隙的形成，体积的物理特性和 生物相容性，主要结果定义了成功的键强度优于现有 没有肽束缚的复合材料，生物相容性等于或优于现有复合材料。在 除了拟议的工作对修复牙科的特定影响外，我们的方法更广泛 潜在影响。提出的技术可以应用于任何粘附问题，包括材料 - 材料，材料生物学和生物生物学粘附，因此适用于多种 组织工程努力，包括骨骼和牙本质组织工程，肌腱和韧带修复，以及 搪瓷形成。