Engineering anti-fragile tooth/restorative interfaces

摘要 尽管几乎所有当代牙科修复材料都表现出足够高的初始粘结强度， 材料，随着时间的推移，粘结的韧性会逐渐受损。债券减少额 强度是机械和/或化学损伤降解基质组织的结果，导致粘合 脆弱性和最终的修复失败。这种失效机制对于V类尤其普遍 缺陷几何形状需要持久的高粘合强度以确保寿命的情况下， 并且由于牙龈的接近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”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 自适应界面，通过使用工程肽，使键强度实际上增加， 对侮辱的回应这项使能技术有望提高V类牙科修复体的寿命 通过使修复体与在pH介导的脱矿作用下暴露的胶原蛋白逐渐结合。的 修复材料也将通过第二组肽与羟基磷灰石结合，因此它们被固定到两者上。 牙本质的有机相和无机相。无机的pH缓冲颗粒将被结合到复合材料中 它本身可以调节局部pH值，延迟由于脱矿作用引起的组织损失。因此，我们提出了一个双重 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，即掺入结合胶原蛋白和/或胶原蛋白的束缚低聚物。 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。为了检验这一中心假设，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，在降低的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， 将牙科清洁剂与基质组织共价结合。 2.在修复体/组织界面结合磷灰石结合寡肽，以进一步改善 修复体附着力 3.基于pH缓冲无机纳米粒子的自缓冲复合材料的合成 能够作为局部pH缓冲剂，减轻化学损伤，并测试 目标1-3中开发的材料系统。 我们将测量界面结合强度、边缘间隙的形成、本体物理性质和 生物相容性，定义成功的主要结果是粘合强度优于现有的粘合强度上级。 不含肽系链的复合材料，生物相容性等于或上级于现有复合材料。在 除了建议的工作对修复牙科的具体影响外，我们的方法还有更广泛的 潜在影响。所提出的技术可以应用于任何粘附问题，包括材料- 材料、材料-生物和生物-生物粘附，因此适用于各种 组织工程的努力，包括骨和牙本质组织工程，肌腱和韧带修复， 釉质形成

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.