Polymer-Antibiotic Conjugates as Antibacterial Additives for Dental Resins

项目摘要 因为细菌感染不仅是龋齿的罪魁祸首，也是导致牙齿失败的主要原因。 修复体，开发具有长期抗菌效果的牙科生物材料是一个重要目标。 尽管已经提出了各种策略来将抗菌特性结合到牙科树脂中， 每种策略都有内在的局限性。爆发释放通常发生在游离抗菌剂 加入树脂中；固定化季铵盐(QAS)对细菌生长的表面抑制 会被生物分子的表面吸附所折衷；颜色稳定性是一个问题，当无机 使用了抗菌填充剂。令人惊讶的是，将抗生素结合到基于聚合物的树脂基质中 抗菌牙科生物材料的开发还没有被探索过。这项提议的核心假设是 是基于聚合物-抗生素结合物(PAC)的牙科修复生物材料可以提供最佳的 抗菌性能，同时保持其良好的物理和生物兼容性。因此，这 该方案旨在系统地制备PAC和含PAC的树脂，并研究其结构和性能 在牙科修复体应用方面的关系，有两个具体目标。具体目标1是开发 PAC和含PAC的牙科树脂。首先将制备单体-抗生素结合物(MACs)。然后 PAC将通过MAC与通常用于牙科胶粘剂的单体聚合来合成 申请。得到的PAC将用作牙科粘合剂中的抗菌添加剂，以准备一个图书馆 含PAC的牙科树脂。将对MAC、PAC和含PAC树脂进行系统表征，以 验证合成是否成功，并揭示其结构特征。具体目标2是了解 PAC和PAC基牙科树脂的抗菌、物理和生物相容性。版本配置文件 将对生物相关条件下的结合抗生素进行研究。它们对细菌的抑制作用将 利用不同的口腔细菌菌种进行系统研究。他们引发抗生素耐药性的风险将会 被评估。将评估它们与牙龈成纤维细胞的生物相容性。他们之间的关系 将对其结构、抗菌性能和生物相容性进行解释。多个因素的协同效应 抗生素和抗生素(S)与固定化QAS的组合将进行研究。机械性能，水 对含PAC树脂的吸附、接触角和颜色稳定性进行了研究。总体而言， 拟议的研究不仅承诺建立PAC和PAC基抗菌药物的合成方法学 树脂，但也提供了对其结构-性能关系的关键见解。这些研究将奠定坚实的基础 为进一步开发用于多种体内临床的含抗生素牙科制剂奠定基础 申请。拟议的研究活动得到了我们的跨学科专业知识的大力支持 课题组和有意义的初步结果，这不仅证明了合成的可行性 环丙沙星为基础的PAC和PAC为基础的树脂，但其显著的抗菌效益。

Project Abstract Because bacterial infection is not only responsible for dental caries but also the main cause of failure of dental restorations, development of dental biomaterials with long-term antibacterial efficacy is an important goal. Although a variety of strategies have been proposed to incorporate antibacterial properties within dental resins, each strategy has intrinsic limitations. Burst release generally occurs when free antibacterial agents are incorporated into resins; surface inhibition of bacterial growth by immobilized quaternary ammonium salt (QAS) can be compromised by surface adsorption of biomolecules; color stability is an issue when inorganic antibacterial fillers are used. Surprisingly, conjugation of antibiotics into the polymer-based resin matrices for the development of antibacterial dental biomaterials has not been explored. The central hypothesis of this proposal is that dental restorative biomaterials based on polymer-antibiotic conjugates (PACs) can offer optimal antibacterial properties, while maintaining their favorable physical and biocompatibility properties. Therefore, this proposal aims to systematically prepare PACs and PAC-containing resins, and study their structure-property relationship in the context of dental restorative applications, with two specific aims. Specific Aim 1 is to develop PACs and PAC-containing dental resins. Monomer-antibiotic conjugates (MACs) will first be prepared. Then PACs will be synthesized by polymerization of MACs with a monomer typically used in dental adhesive applications. The resulting PACs will be used as antibacterial additives in dental adhesives to prepare a library PAC-containing dental resins. MACs, PACs and PAC-containing resins will be systematically characterized to verify the success of the synthesis and to reveal their structural features. Specific Aim 2 is to understand the antibacterial, physical and biocompatibility properties of PACs and PAC-based dental resins. The release profiles of conjugated antibiotics under bio-relevant conditions will be investigated. Their bacterial inhibition effects will be studied systematically by using different oral bacterial species. Their risk of inducing antibiotic resistance will be evaluated. Their biocompatibility with gingival fibroblasts will be assessed. The relationship between their structures, antibacterial properties and biocompatibility will be interpreted. Synergistic effects of multiple antibiotics and combinations of antibiotic(s) with immobilized QAS will be studied. Mechanical properties, water adsorption, contact angle and color stability of the PAC-containing resins will be investigated. Overall, the proposed studies promise to not only establish the synthetic methodology for PACs and PAC-based antibacterial resins, but also provide key insights into their structure-property relationship. These studies will lay a solid foundation for the further development of antibiotic-containing dental formulations for a variety of in vivo clinical applications. The proposed research activities are strongly supported by the interdisciplinary expertise of our research team and the significant preliminary results, which demonstrate not only the feasibility of the synthesis of ciprofloxacin-based PACs and PAC-based resins, but also their remarkable antibacterial benefits.