Modification of Titanium Substrates with Chimeric Peptides Comprising Antimicrobial and Titanium-Binding Motifs Connected by Linkers To Inhibit Biofilm Formation
Modification of Titanium Substrates with Chimeric Peptides Comprising Antimicrobial and Titanium-Binding Motifs Connected by Linkers To Inhibit Biofilm Formation
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用包含通过接头连接的抗菌剂和钛结合基序的嵌合肽修饰钛基底以抑制生物膜形成
DOI：
10.1021/acsami.5b11949
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发表时间：
2016-03-02
影响因子：
9.5
通讯作者：
Gao, Ping
中科院分区：
文献类型：
--
作者：
Liu, Zihao;Ma, Shiqing;Gao, Ping
细菌粘附和生物膜形成是种植体相关感染的主要原因，这种感染很难消除，并可能导致牙种植体失败。具有结合和抗菌基序的嵌合肽可能提供一种有前景的替代方案来抑制钛表面生物膜的形成。在本研究中，通过直接连接抗菌基序（JH8194：KRLFRRWQWRMKKY）与结合基序（minTBP-1：RKLPDA）或通过柔性/刚性接头来修饰钛表面来设计嵌合肽。我们使用石英晶体微天平（QCM）和原子力显微镜（AFM）技术评估了肽的结合行为，并研究了用这些肽修饰钛表面对戈登链球菌（S. gordonii）和血链球菌（S. sanguis）生物活性的影响。与柔性接头（GGGGS）相比，刚性接头（PAPAP）显着增加了嵌合肽在钛表面的吸附（p < 0.05）。浓度依赖性吸附符合单域 Langmuir 模型，而时间依赖性吸附符合两域 Langmuir 模型。此外，具有刚性接头的嵌合肽比具有柔性接头的肽表现出更有效的抗菌能力。这一发现归因于刚性接头能够分离功能域并最大程度地减少它们的干扰。因此，具有特定钛结合基序和抗细菌基序的嵌合肽的性能可以通过正确选择接头来优化。这种嵌合肽的合理设计为抑制钛表面生物膜的形成提供了一种有前途的替代方案，并有可能预防种植体周围炎和种植体周围粘膜炎。
Bacterial adhesion and biofilm formation are the primary causes of implant-associated infection, which is difficult to eliminate and may induce failure in dental implants. Chimeric peptides with both binding and antimicrobial motifs may provide a promising alternative to inhibit biofilm formation on titanium surfaces. In this study, chimeric peptides were designed by connecting an antimicrobial motif (JH8194: KRLFRRWQWRMKKY) with a binding motif (minTBP-1: RKLPDA) directly or via flexible/rigid linkers to modify Ti surfaces. We evaluated the binding behavior of peptides using quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques and investigated the effect of the modification of titanium surfaces with these peptides on the bioactivity of Streptococcus gordonii (S. gordonii) and Streptococcus sanguis (S. sanguis). Compared with the flexible linker (GGGGS), the rigid linker (PAPAP) significantly increased the adsorption of the chimeric peptide on titanium surfaces (p < 0.05). Concentration-dependent adsorption is consistent with a single Langmuir model, whereas time-dependent adsorption is in line with a two-domain Langmuir model. Additionally, the chimeric peptide with the rigid linker exhibited more effective antimicrobial ability than the peptide with the flexible linker. This finding was ascribed to the ability of the rigid linker to separate functional domains and reduce their interference to the maximum extent. Consequently, the performance of chimeric peptides with specific titanium-binding motifs and antimicrobial motifs against bacteria can be optimized by the proper selection of linkers. This rational design of chimeric peptides provides a promising alternative to inhibit the formation of biofilms on titanium surfaces with the potential to prevent peri-implantitis and peri-implant mucositis.