Polymer-Antibiotic Conjugates as Antibacterial Additives for Dental Resins

聚合物-抗生素复合物作为牙科树脂的抗菌添加剂

• 批准号: 9975136
• 负责人: Chong Cheng
• 金额: $ 19.7万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-09 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975136
• 关键词: Adhesives; Adsorption; Advanced Development; Adverse effects; Affect; Aging; Ammonium; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Infections; Behavior; Biocompatible Materials; Bromides; Carbohydrates; Chemicals; Chlorhexidine; Chronic; Ciprofloxacin; Color; Combined Antibiotics; Composite Dental Resin; Dental; Dental Restoration Failure; Dental caries; Dental crowns; Dentistry; Dentures; Development; Effectiveness; Esterification; Fibroblasts; Filler; Formulation; Foundations; Gingiva; Goals; Growth; Healthcare; Immobilization; In Vitro; Incidence; Industry; Libraries; Link; Methacrylates; Methodology; Microbial Biofilms; Minerals; Molecular Weight; Odontogenesis; Oral; Orthodontic Appliances; Patients; Plant Resins; Polymers; Property; Pulp Canals; Recurrence; Reporting; Research; Research Activity; Research Personnel; Risk; Salts; Sodium Chloride; Solid; Streptococcus mutans; Structure; Surface; Tensile Strength; Testing; Therapeutic; Time; Tooth Loss; Varnish; Water; antimicrobial drug; base; biomaterial compatibility; cariogenic bacteria; chemical property; clinical application; controlled release; cost; cytotoxicity; dental adhesive; dental resin; dosage; in vivo; insight; interfacial; mechanical properties; microbial disease; monomer; nanomaterials; novel; organic acid; polymerization; prevent; restoration; restorative dentistry; seal; success

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.

项目摘要 因为细菌感染不仅是造成龋齿的原因，也是导致牙科失败的主要原因。 修复体中，开发具有长期抗菌功效的牙科生物材料是一个重要目标。 尽管已经提出了多种策略来将抗菌特性融入牙科树脂中， 每种策略都有其内在的局限性。当游离抗菌剂被释放时，通常会发生突释。 掺入树脂中；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；当无机物时，颜色稳定性是一个问题 使用抗菌填料。令人惊讶的是，将抗生素缀合到基于聚合物的树脂基质中 抗菌牙科生物材料的开发尚未被探索。本提案的中心假设 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 抗菌特性，同时保持其良好的物理和生物相容性。因此，这 该提案旨在系统地制备 PAC 和含 PAC 的树脂，并研究其结构性能 牙科修复应用背景下的关系，有两个具体目标。具体目标 1 是发展 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 与牙科粘合剂中常用的单体聚合来合成 应用程序。所得 PAC 将用作牙科粘合剂中的抗菌添加剂，以制备库 含有 PAC 的牙科树脂。 MAC、PAC 和含 PAC 的树脂将被系统地表征 验证合成成功并揭示其结构特征。具体目标 2 是了解 PAC 和基于 PAC 的牙科树脂的抗菌、物理和生物相容性特性。发布简介 将研究生物相关条件下缀合抗生素的作用。它们的细菌抑制作用将 通过使用不同的口腔细菌物种进行系统研究。它们诱发抗生素耐药性的风险将 进行评估。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 将解释结构、抗菌特性和生物相容性。多种协同效应 将研究抗生素以及抗生素与固定化 QAS 的组合。机械性能，水 将研究含 PAC 的树脂的吸附、接触角和颜色稳定性。总体而言， 拟议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，还提供了对其结构与性能关系的重要见解。这些研究将为 为进一步开发用于各种体内临床的含抗生素牙科制剂奠定了基础 应用程序。拟议的研究活动得到了我们跨学科专业知识的大力支持 研究团队和重要的初步结果，不仅证明了合成的可行性 环丙沙星 PAC 和 PAC 树脂的优点，而且还具有显着的抗菌功效。

项目成果

Synthesis and antibacterial activity of polymer-antibiotic conjugates incorporated into a resin-based dental adhesive.

树脂基牙科粘合剂中聚合物-抗生素缀合物的合成和抗菌活性。

• 发表时间: 2021-03-21
• 影响因子: 6.6
• 作者: Zhang, Ziwen;Jones, Megan M;Sabatini, Camila;Vanyo, Stephen T;Yang, Ming;Kumar, Abhishek;Jiang, Yancheng;Swihart, Mark T;Visser, Michelle B;Cheng, Chong
• 通讯作者: Cheng, Chong

Mechanical characterization and adhesive properties of a dental adhesive modified with a polymer antibiotic conjugate.

用聚合物抗生素缀合物改性的牙科粘合剂的机械特性和粘合性能。

• 发表时间: 2022-05
• 作者: Sabatini, Camila;Aguilar, Russell J.;Zhang, Ziwen;Makowka, Steven;Kumar, Abhishek;Jones, Megan M.;Visser, Michelle B.;Swihart, Mark;Cheng, Chong
• 通讯作者: Cheng, Chong