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Antimicrobial Peptide–Polymer Conjugates for Dentistry
ACS Applied Polymer Materials ( IF 5 ) Pub Date : 2020-01-14 , DOI: 10.1021/acsapm.9b00921
Sheng-Xue Xie 1 , Linyong Song 1 , Esra Yuca 2 , Kyle Boone 1 , Rizacan Sarikaya 1 , Sarah Kay VanOosten 1 , Anil Misra 1 , Qiang Ye 1 , Paulette Spencer 1 , Candan Tamerler 1
Affiliation  

Bacterial adhesion and growth at the composite/adhesive/tooth interface remain the primary cause of dental composite restoration failure. Early colonizers, including Streptococcus mutans, play a critical role in the formation of dental caries by creating an environment that reduces the adhesive’s integrity. Subsequently, other bacterial species, biofilm formation, and lactic acid from S. mutans demineralize the adjoining tooth. Because of their broad spectrum of antibacterial activity and low risk for antibiotic resistance, antimicrobial peptides (AMPs) have received significant attention to prevent bacterial biofilms. Harnessing the potential of AMPs is still very limited in dentistry—a few studies have explored peptide-enabled antimicrobial adhesive copolymer systems using mainly nonspecific adsorption. In the current investigation, to avoid limitations from nonspecific adsorption and to prevent potential peptide leakage out of the resin, we conjugated an AMP with a commonly used monomer for dental adhesive formulation. To tailor the flexibility between the peptide and the resin material, we designed two different spacer domains. The spacer-integrated antimicrobial peptides were conjugated to methacrylate (MA), and the resulting MA–AMP monomers were next copolymerized into dental adhesives as AMP–polymer conjugates. The resulting bioactivity of the polymethacrylate-based AMP conjugated matrix activity was investigated. The antimicrobial peptide conjugated to the resin matrix demonstrated significant antimicrobial activity against S. mutans. Secondary structure analyses of conjugated peptides were applied to understand the activity differential. When mechanical properties of the adhesive system were investigated with respect to AMP and cross-linking concentration, resulting AMP–polymer conjugates maintained higher compressive moduli compared to hydrogel analogues including polyHEMA. Overall, our result provides a robust approach to develop a fine-tuned bioenabled peptide adhesive system with improved mechanical properties and antimicrobial activity. The results of this study represent a critical step toward the development of peptide-conjugated dentin adhesives for treatment of secondary caries and the enhanced durability of dental composite restorations.

中文翻译:

用于牙科的抗菌肽-聚合物缀合物

复合材料/粘合剂/牙齿界面处的细菌粘附和生长仍然是牙科复合材料修复失败的主要原因。包括变形链球菌在内的早期定殖者通过创造降低粘合剂完整性的环境,在龋齿的形成中发挥着关键作用。随后,其他细菌种类、生物膜形成和来自变形链球菌的乳酸使相邻牙齿脱矿质。由于抗菌肽(AMP)具有广谱抗菌活性和低抗生素耐药性风险,其在预防细菌生物膜方面受到了广泛关注。在牙科领域利用 AMP 的潜力仍然非常有限——一些研究主要利用非特异性吸附来探索肽类抗菌粘合剂共聚物系统。在当前的研究中,为了避免非特异性吸附的限制并防止潜在的肽从树脂中泄漏,我们将 AMP 与牙科粘合剂配方中常用的单体缀合。为了调整肽和树脂材料之间的灵活性,我们设计了两种不同的间隔域。将间隔基整合的抗菌肽与甲基丙烯酸酯 (MA) 缀合,然后将所得的 MA-AMP 单体作为 AMP-聚合物缀合物共聚到牙科粘合剂中。研究了基于聚甲基丙烯酸酯的 AMP 共轭基质活性的生物活性。与树脂基质缀合的抗菌肽对变形链球菌表现出显着的抗菌活性。应用缀合肽的二级结构分析来了解活性差异。当根据 AMP 和交联浓度研究粘合剂系统的机械性能时,所得 AMP-聚合物缀合物与包括聚 HEMA 在内的水凝胶类似物相比保持了更高的压缩模量。总体而言,我们的结果提供了一种稳健的方法来开发具有改进的机械性能和抗菌活性的微调生物肽粘合剂系统。这项研究的结果代表了开发用于治疗继发性龋齿和增强牙科复合修复体耐久性的肽缀合牙本质粘合剂的关键一步。
更新日期:2020-01-15
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