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 因为细菌感染不仅负责龋齿，而且是牙齿失败的主要原因 恢复，具有长期抗菌功效的牙齿生物材料的发展是一个重要目标。 尽管已经提出了各种策略将抗菌特性纳入牙科树脂，但 每个策略都有内在的局限性。当游离抗菌剂为时，通常会发生爆发 掺入树脂中；通过固定的第四纪铵盐（QAS）对细菌生长的表面抑制 可以通过生物分子的表面吸附来损害；颜色稳定性是无机的问题 使用抗菌填充剂。令人惊讶的是，将抗生素结合到基于聚合物的树脂矩阵中 尚未探索抗菌牙齿生物材料的发展。该提议的中心假设 是基于聚合物 - 抗生素结合物（PAC）的牙齿恢复性生物材料可以提供最佳 抗菌特性，同时保持其良好的物理和生物相容性特性。因此，这个 提案旨在系统地准备PAC和PAC的树脂，并研究其结构范围 在牙科修复应用的背景下，有两个具体目标。特定目的1是发展 PACS和含PAC的牙科树脂。首先要准备单体抗生素结合物（MAC）。然后 PACS将通过通常用于牙科粘合剂中的单体聚合Mac的聚合来合成 申请。由此产生的PAC将用作牙科粘合剂中的抗菌添加剂，以准备库 含PAC的牙科树脂。 Mac，PAC和含PAC的树脂将被系统地表征为 验证合成的成功并揭示其结构特征。具体目标2是了解 PACS和基于PAC的牙科树脂的抗菌，物理和生物相容性特性。发行轮廓 将研究在生物相关条件下的共轭抗生素。它们的细菌抑制作用将 通过使用不同的口服细菌物种系统地研究。他们诱导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 结构，抗菌特性和生物相容性将被解释。多重的协同作用 将研究抗生素和抗生素与固定QA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， 拟议的研究有望不仅建立基于PAC和PAC抗菌的合成方法 树脂，但也提供了有关其结构 - 陶艺关系的关键见解。这些研究将扎实 为各种体内临床的进一步开发含抗生素的牙齿制剂的基础 申请。拟议的研究活动得到了我们的跨学科专业知识的强烈支持 研究团队和重要的初步结果，不仅证明了综合的可行性 基于环丙沙星的PAC和基于PAC的树脂的含量，但它们的显着抗菌益处。

项目成果

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

• DOI: 10.1016/j.jmbbm.2022.105153
• 发表时间: 2022-05
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 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

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

• DOI: 10.1039/d0bm01910k
• 发表时间: 2021-03-21
• 期刊: Biomaterials science
• 影响因子: 6.6
• 作者: Zhang Z ;Jones MM ;Sabatini C ;Vanyo ST ;Yang M ;Kumar A ;Jiang Y ;Swihart MT ;Visser MB ;Cheng C
• 通讯作者: Cheng C