Engineering anti-fragile tooth/restorative interfaces

摘要 尽管几乎所有当代牙科修复剂都表现出足够高的初始粘结强度 材料，随着时间的推移，这种结合的韧性可能会逐渐减弱。债券减持 强度是由于机械和/或化学伤害使基质组织退化，从而导致粘合 脆弱性，并最终导致修复失败。这种失效机制在V类中尤为普遍 修复体的缺陷几何形状需要持久的高粘结强度以确保寿命 并且由于接近牙床而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底层牙体之间设计抗脆性界面 牙齿衬底。本研究的临床意义和创新之处在于发展了一种 通过使用工程化的多肽实现自适应接口，从而使结合强度实际增加 对侮辱的回应。这项使能技术有望提高V类牙修复体的寿命 通过使修复逐渐与pH介导的脱矿后暴露的胶原蛋白结合。这个 修复材料还将通过第二组多肽与羟基磷灰石结合，从而将它们附着在两种材料上 牙本质的有机和无机相。无机的pH缓冲颗粒将被加入到复合材料中 它本身能够调节局部的PH值，延缓因脱矿造成的组织丢失。因此，我们提出了一个双重的 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 修复体的寿命。 我们将测试中心假设，即结合与胶原和/或 牙齿表面的磷灰石和复合树脂上的官能团将提高粘结强度 时间和酸性条件下。为了检验这一中心假设，我们的具体目标和次要假设是： 1.开发具有(I)动态共价官能团的低聚物，其在降低pH的条件下， 与胶原结合的赖氨酸残基或醛和酮的胺基团反应 由翻译后赖氨酸修饰产生的基团，和(Ii)可聚合的侧基 将牙科修复剂与基材组织共价结合。 2.在修复体/组织界面引入磷灰石结合寡肽，进一步改善 修复粘连。 3.合成基于pH缓冲无机纳米颗粒的自缓冲复合材料 它们能够起到局部pH缓冲剂的作用，减轻化学损害，并测试 AIMS 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，整体物理性能和 生物相容性，决定成功的主要结果是结合强度高于现有的 不含肽的复合材料，生物相容性与现有复合材料相当或更好。在……里面 除了拟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影响 潜在的影响。建议的技术可应用于任何粘合问题，包括材料- 材料、材料-生物和生物-生物粘合，因此适用于各种 组织工程，包括骨和牙本质组织工程，肌腱和韧带修复，以及 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.