APPLICATION OF CLICK CHEMISTRY IN THE DEVELOPMENT OF NOVEL DENTAL ADHESIVES

描述（由申请人提供）：本提案的科学目标是开发合理设计的新型单体，当其配制成牙科粘合剂时，将大大改善粘合剂/牙本质的结合，从而显着延长树脂基牙齿修复体的寿命。点击化学在目标新单体的设计和合成中起着至关重要的作用，因为模块化合成方法的核心是点击化学在温和条件下选择性和高效地将有机组分连接在一起，而不影响每个有机组分携带的敏感官能团。提出的研究源于牙科修复长期面临的关键挑战：基于复合树脂的牙科修复体失败率高得令人望而却步。过早失效的一个主要原因是复合树脂与牙本质之间缺乏紧密和持久的密封。目前最先进的牙科粘合剂无法形成紧密的粘合剂/牙本质（a/d）密封是由于三个主要因素。首先，树脂与牙本质胶原蛋白之间的结合很差，这种结合依赖于树脂聚合物与暴露的胶原原纤维的浸润和随后的缠结。微机械联锁机制本身就存在问题，因为渗透不足、聚合不完全和溶剂膨胀都阻碍了紧密a/d键的形成。其次，暴露/未保护的牙本质胶原蛋白的稳定性和机械强度往往较低。当复合树脂附着的基础本身就摇摇欲坠时，实现持久修复不仅具有挑战性，而且是不可能的。第三，渗透树脂聚合物的强度通常较差，主要是由于当前单体在水环境下不完全聚合。在这个提议中，新的单体设计同时解决这三个关键问题，将使用“点击化学”合成。这些单体具有以下独特的特点：1)它们具有许多水解稳定的可聚合甲基丙烯酰胺基团，确保了高单体/聚合物转化率；2)含有保护醛基团，可水解去保护，交联暴露的胶原，显著提高胶原的生物稳定性和机械强度；3)醛类水解脱保护产生亲水性树脂枝，有利于树脂渗透到水合胶原蛋白中，不产生脱落的小分子；4)交联胶原蛋白与树脂共价结合，形成紧密稳定的a/d键。创新的技术，包括FTIR和微拉曼化学成像，拉伸强度测试等，将被用来彻底表征新设计的单体基粘合剂如何聚合和与牙本质相互作用。目标不仅是确认设计原则和合成单体的工作，而且要深入了解它们是如何以及为什么这样做的。

DESCRIPTION (provided by applicant): The scientific objective of this proposal is to develop judiciously designed novel monomers which when formulated into a dental adhesive will drastically improve the adhesive/dentin bonding, thus significantly extending the longevity of resin-based tooth restorations. Click chemistry plays an essential role in the design and synthesis of the targeted novel monomers as the modular synthetic approach centers on the ability of click chemistry to link organic components together selectively and efficiently under mild conditions without affecting sensitive functional groups carried by each organic component. The proposed research stems from the critical challenge long facing restorative dentistry: dental restorations based on composite resins have a prohibitively high failure rate. One primary reason for the premature failure is the lack of a tight and long-lasting seal between the composite resin and the underline dentin. The inability of the current state-of-the-art dental adhesives to form a tight adhesive/dentin (a/d) seal is due to three major factors. First, the bonding between resin and dentin collagen, which relies on the infiltration and subsequent entanglement of resin polymers with exposed collagen fibrils, is poor. The micromechanical interlocking mechanism is intrinsically problematic as insufficient penetration, incomplete polymerization and solvent swelling all prohibit the formation of a tight a/d bonding. Second, the stability and mechanical strength of the exposed/unprotected dentin collagen is often low. When the foundation to which composite resins adhere is itself shaky, achieving long-lasting restoration is not just challenging, but impossible. Third, the strength of infiltrated resin polymers is usually poor due chiefly to the incomplete polymerization of current monomers under aqueous environment. In this proposal, novel monomers designed to address all three critical issues simultaneously will be synthesized using "click chemistry". Such monomers have the following unique features: 1) They have a number of hydrolytically stable polymerizable methacrylamide groups, ensuring high monomer/polymer conversion; 2) They include protected aldehyde groups which can be hydrolytically deprotected and subsequently crosslink exposed collagen, thus significantly enhancing the collage biostability and mechanical strength; 3) Hydrolytic deprotection of aldehydes yields hydrophilic resin branches, which facilitate resin permeation to hydrated collagen and produces no breakaway small molecules; and 4) Crosslinked collagen is covalently bonded to resin, creating a tight and stable a/d bond. Innovative techniques, including FTIR and micro-Raman chemical imaging, tensile strength testing, etc will be utilized to thoroughly characterize how the newly designed monomer-based adhesives polymerize and interact with dentin. The goal is not only to confirm that the design principles and the synthesized monomers work, but also to gain deep understanding into how and why they do. PUBLIC HEALTH RELEVANCE: The proposed research, if successfully carried out, will significantly increase the lifetime of resin based tooth restorations, thus positively impact the public health. It will also benefit the environment as the resin based restoration will gain additional advantage over amalgam.