Polymer-Antibiotic Conjugates as Antibacterial Additives for Dental Resins

项目摘要 由于细菌感染不仅是龋病的主要原因，也是导致牙科失败的主要原因， 因此，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， 每一种战略都有其内在的局限性。突释通常发生在当游离抗菌剂 结合到树脂中;通过固定化季铵盐（QAS）表面抑制细菌生长 可能会受到生物分子表面吸附的影响;当无机 使用抗菌填料。令人惊讶的是，将抗生素缀合到聚合物基树脂基质中以用于制备抗生素。 抗菌牙科生物材料的开发还没有被探索。这项提议的核心假设是 基于聚合物-抗生素缀合物（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相容性。因此本 本课题旨在系统地制备PAC及含PAC的树脂，并对其结构与性能进行研究 在牙科修复应用的背景下，有两个特定的目标。具体目标1：发展 PAC和含PAC的牙科树脂。首先制备单体-抗生素缀合物（MAC）。然后 PAC将通过MAC与通常用于牙科粘合剂的单体聚合来合成 应用.由此产生的PAC将用作牙科粘合剂中的抗菌添加剂，以制备库 含PAC的牙科树脂。将系统地表征MAC、PAC和含PAC的树脂， 验证合成的成功性并揭示其结构特征。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。的释放曲线 将研究在生物相关条件下结合抗生素的活性。它们的抑菌作用将 通过使用不同的口腔细菌物种进行系统研究。它们诱导抗生素耐药性的风险将 被评价。将评估其与牙龈成纤维细胞的生物相容性。的相关性 结构，抗菌性能和生物相容性将被解释。多重协同效应 将研究抗生素和抗生素与固定化QAS的组合。机械性能，水 将研究含PAC树脂的吸附、接触角和颜色稳定性。总体看 提出的研究不仅有望建立PAC和基于PAC的抗菌剂的合成方法， 树脂，而且还提供了关键的见解，他们的结构-性能关系。这些研究将奠定坚实的 为进一步开发用于各种体内临床的含抗生素的牙科制剂奠定了基础 应用.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。 研究小组和显着的初步结果，这不仅证明了合成的可行性 环丙沙星基PAC和PAC基树脂的优点，以及它们显著的抗菌功效。

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.