Dental Composite Materials Based on Photoinitiated Thiol-Vinyl Sulfone Reactions

描述（由申请人提供）：牙科修复是概念上最简单的生物材料之一-基本上需要以美学上可接受的方式恢复机械功能。然而，尽管概念简单，但一系列复杂且经常相互冲突的材料，生物，固化和反应特性需要一系列次优解决方案。每年进行数亿次牙齿矫正，这些牙齿矫正的过早失败导致需要进行更多数量的牙齿矫正，包括偶尔去除额外的健康牙齿结构。对简单的、生物相容的、易于操作的美学牙科清洁剂的需求已经将社区推向易于原位反应（通常通过光引发）的聚合物复合材料，以产生外观上类似牙齿的高模量、高强度复合结构。尽管这些材料很重要，但树脂（即，这些体系的可聚合组分）相自几十年前引入以来基本保持不变。通常使用基于二甲基丙烯酸酯的树脂用于牙科修复材料受到关键问题的困扰;它们不能实现甲基丙烯酸酯的完全转化，因此留下大量可以提取到口腔环境中的材料。此外，这些材料易于发生显著的收缩和收缩应力，所述收缩和收缩应力在用于固化材料的聚合/固化过程期间产生。因此，在这里，我们提出了一个革命性的新方法，牙科材料的基础上亲核催化硫醇-乙烯砜网络形成反应。所提出的硫醇-乙烯基砜牙科复合材料系统将显著改善传统的基于甲基丙烯酸酯的复合材料系统的生物、化学反应和机械性能。基于令人兴奋的初步结果，证明了通过这种高效，快速的反应实现完全官能团转化的能力;形成的聚合物的适当机械行为;低收缩和应力;以及从树脂中消除酶反应性官能团，我们假设通过这种硫醇-乙烯基砜反应形成的树脂代表了牙科修复材料的理想候选物。总体目标是开发和评估基于亲核试剂催化的硫醇-乙烯基砜迈克尔加成反应的牙科复合材料，包括开发适当的单体和官能化填料，开发这些树脂的高反应性光引发剂系统，以及证明可接受的疲劳、可浸提物、生物相容性、降解和其他基本的短期和长期复合材料行为。最终，总体目标是将这些硫醇-乙烯基砜基复合材料作为牙科复合材料领域的颠覆性变化。我们将在此授权期内证明，这些材料能够在长期环境挑战性测试条件下大幅减少可浸提物、溶胀、降解和磨损，从而将使用寿命延长两倍以上。

DESCRIPTION (provided by applicant): Dental restorations represent one of the conceptually simplest biomaterials - essentially requiring the restoration of mechanical function in an aesthetically acceptable manner. Yet, despite that conceptual simplicity, an array of complex and often conflicting material, biological, curing and reaction properties necessitate a series of suboptimal solutions. Hundreds of millions of restorations are performed each year and premature failure of these restorations results in the need for a far greater number of restorations, including the occasional removal of additional healthy tooth structure. The need for simple, biocompatible, easily manipulated aesthetic dental restoratives has pushed the community towards polymeric composites that are readily reacted in situ, generally by photoinitiation, to yield a high modulus, high strength composite structure that is tooth-like in appearance. Despite the importance of these materials, the resin (i.e., the polymerizable component) phase of these systems has remained largely unchanged since its introduction several decades ago. The common use of dimethacrylate-based resins for dental restorative materials is plagued by critical problems; they do not achieve complete conversion of the methacrylates and thus leave a great deal of material that can be extracted into the oral environment. Further, these materials are prone to significant shrinkage and shrinkage stress that arises during the polymerization/curing process that is used to set the material. Thus, here, we propose a revolutionary new approach to dental materials based on the nucleophile- catalyzed thiol-vinyl sulfone network forming reaction. The proposed thiol-vinyl sulfone dental composite system will significantly improve upon the biological, chemical reaction and mechanical behavior of traditional methcrylate based composite systems. Based on exciting preliminary results that demonstrate the ability to achieve complete functional group conversion via this highly efficient, rapid reaction; appropriate mechanical behavior from the polymers formed; low shrinkage and stress; and the elimination of enzymatically reactive functional groups from the resin, we hypothesize that resins formed by this thiol-vinyl sulfone reaction represent ideal candidates as dental restorative materials. The overall aim is to develop and evaluate dental composites based on the nucleophile catalyzed thiol-vinyl sulfone Michael addition reaction that will include the development of appropriate monomers and functionalized fillers, the development of highly reactive photoinitiator systems for these resins, and the demonstration of acceptable fatigue, extractables, biocompatibility, degradation and other essential short- and long-term composite behavior. Ultimately, the overall aim is to establish these thiol-vinyl sulfone-based composites as a disruptive change in the dental composite field. We will demonstrate over the course of this grant period that these materials are capable of achieving more than a two-fold increase in service lifetime based on dramatically reduced extractables, swelling, degradation and wear in longterm, environmentally challenging testing conditions.