Oxarane-Acrylate System to Double the Clinical Service Life of Restorative Resins

描述（由申请人提供）：为了开发具有至少两倍于基于Bis-GMA/TEGDMA的复合材料的寿命的新型修复系统，必须克服它们的不完全固化和对水解和酯酶降解的敏感性。为了解决这些问题，我们将开发一种基于环氧乙烷/丙烯酸酯互穿网络系统（OASys，发音为Oasis）的新型超疏水、抗降解牙科修复材料。这些基于具有二环氧乙烷或二丙烯酸酯官能度的氟化双烯丙基醚的新型单体可以高度转化以形成疏水的、抗降解的、坚韧的和弹性的互穿聚合物网络（IPN），该互穿聚合物网络本身是高度交联的。就其性质而言，这些特性赋予低残余应力、高抗水解和酶降解性以及生物相容性。我们还将开发一种新的一步（无底漆），“智能”，抗菌粘合树脂与原位生成的，无色和颜色稳定，银纳米粒子（AgNPs）。粘合树脂将含有磷酸酯基团加上环氧乙烷和丙烯酸酯官能团。环氧乙烷和丙烯酸酯官能团键合到IPN树脂基质中的相应官能团上，可能比常规甲基丙烯酸酯体系键合更强。磷酸盐基团将允许粘合树脂润湿蚀刻的矿物表面以及直接粘合到钙磷酸盐矿物结构中的钙。在边缘间隙形成的情况下，“智能”原位生成的AgNP将释放Ag+离子并创造抗菌环境，从而进一步降低复发性龋齿的发生率。提出了五个具体目标：1。确定使用环氧乙烷、增加疏水性和IPN对树脂机械性能、物理性能和体外生物相容性的影响。更有前途的组合物将与增强填料组合并用于目标2。2.研究4-磷酸-NPG-GA环氧乙烷（4POA）基粘接体系和原位生成的银纳米粒子（AgNP）对环氧乙烷/丙烯酸酯互穿网络复合材料粘接树脂力学性能、物理性能、体外生物相容性和抗菌活性以及粘接强度的影响。两种性能最好的复合材料将被选择用于后续目标。3.确定使用环氧乙烷、增加的疏水性和IPN对树脂对口腔生化环境的耐受性的影响。在目标2中选择的两个表现最好的组将在暴露于酸性、碱性和含酯酶的环境90天后进行疲劳和磨损测试。4.确定使用环氧乙烷、增加疏水性和IPN对树脂耐细菌降解性的影响。Aim 2中表现最好的两组将在一个人工环境中进行测试。 口腔细菌生物膜模型。5.确定OASys的体内生物相容性。将在三种体内生物相容性模型中测试表现最好的OASys：迟发型超敏反应、口腔粘膜刺激以及牙髓和牙本质反应测试。

DESCRIPTION (provided by applicant): In order to develop a novel restorative system with at least twice the lifetime of Bis-GMA/TEGDMA- based composites, their incomplete cure and susceptibility to hydrolysis and esterase degradation must be overcome. To address these problems, we will develop a novel superhydrophobic, degradation-resistant, dental restorative based on an Oxirane/Acrylate interpenetrating network System (OASys, pronounced Oasis). These novel monomers based on fluoridated urethanes with either dioxirane or diacrylate functionality can be highly converted to form a hydrophobic, degradation-resistant, tough and resilient interpenetrating polymer network (IPN) that is inherently highly crosslinked. By their nature, these characteristics impart low residual stresses, high resistance to hydrolytic and enzymatic degradation, and biocompatibility. We will also develop a novel one-step (primer-less), "smart," antimicrobial bonding resin with in situ-generated, colorless and color stable, silver nanoparticles (AgNPs). The bonding resin will contain a phosphate group plus both oxirane and acrylate functionalities. The oxirane and acrylate functionalities bond to the corresponding functionalities in the IPN resin matrix for potentially a much stronger bond than the conventional methacrylate system. The phosphate group will allow the bonding resin to wet etched mineral surfaces as well as bond directly to calcium in Ca-phosphate mineral structures. In the event of marginal gap formation, the "smart" in situ-generated AgNPs will release Ag+ ions and create an antibacterial environment, thereby further reducing the incidence of recurrent caries. Five specific aims are proposed: 1. To determine the effect of using oxiranes, increased hydrophobicity, and IPNs on resin mechanical properties, physical properties and in vitro biocompatibility. The more promising compositions will be combined with reinforcing filler and used for Aim 2. 2. To determine the effect of using a 4- Phospho-NPG GA oxirane (4POA)-based bonding system and in situ-generated silver nanoparticles (AgNP) on bonding resin mechanical properties, physical properties, and in vitro biocompatibility and antibacterial activit, as well as on bond strength to oxirane/acrylate interpenetrating network composites. The two best- performing composites will be chosen for subsequent aims. 3. To determine the effect of using oxiranes, increased hydrophobicity, and IPNs on resin resistance to the oral biochemical environment. The two best- performing groups chosen in Aim 2 will be fatigue- and wear-tested after exposure to acidic, basic and esterase-containing environments for 90 days. 4. To determine the effect of using oxiranes, increased hydrophobicity, and IPNs on resin resistance to bacterial degradation. The two best-performing groups from Aim 2 will be tested in an artificial mouth bacterial biofilm model. 5. To determine the in vivo biocompatibility of the OASys. The best performing OASys will be tested in three in vivo biocompatibility models: delayed-type hypersensitivity, oral mucosa irritation, and pulp and dentin response tests.