Directed assembly of PEGylated-peptide coatings for infection-resistant titanium metal.

Directed assembly of PEGylated-peptide coatings for infection-resistant titanium metal.
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DOI:
10.1021/ja9020827
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发表时间:
2009-08-12
影响因子:
15
通讯作者:
Grinstaff MW
Grinstaff MW
中科院分区:
化学1区
文献类型:
--
作者:
Khoo X;Hamilton P;O'Toole GA;Snyder BD;Kenan DJ;Grinstaff MW

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材料及其周围生物环境之间的适当表面化学对于任何植入物(无论是金属、塑料还是陶瓷)的最终整合和性能至关重要。描述了一种能够通过非共价结合容易地修饰钛(Ti)金属表面的稳健的基于肽的涂层技术。使用噬菌体展示筛选过程鉴定具有对Ti的亲和力的短肽,并使用固相化学合成进行氨基酸置换。通过这些研究,HKH三肽基序被阐明为Ti结合肽内Ti结合的重要贡献者。该肽自发地和选择性地吸附到Ti表面上,从稀水溶液中,通过ELISA和石英晶体微天平与耗散监测(QCM-D)确定的亚微摩尔结合亲和力,通过一个主要由静电相互作用主导的过程。原子力显微镜(AFM)显示了一个密集的肽吸附层,平均高度约为0.5 nm。随后,肽的PEG化类似物显示出快速涂覆Ti以提供无污染表面,其有效地阻断纤连蛋白的吸附并显著降低金黄色葡萄球菌附着和体外生物膜形成的程度。这些聚乙二醇化肽涂层有望解决植入金属常见的两个主要障碍:(i)非特异性蛋白质吸附和(ii)细菌定植。同时,简单的一步改性过程将促进这些涂层在手术室中的即时应用。
Appropriate surface chemistry between a material and its surrounding biological environment is crucial to the eventual integration and performance of any implant, whether metal, plastic, or ceramic. A robust peptide-based coating technology capable of easily modifying the surface of titanium (Ti) metal through noncovalent binding is described. A short peptide possessing affinity for Ti was identified using a phage display screening process and subjected to an amino acid substitution exercise using solid-phase chemical synthesis. Through these studies, the HKH tripeptide motif was elucidated as an important contributor to Ti binding within the Ti-binding peptide. This peptide spontaneously and selectively adsorbs onto a Ti surface from dilute aqueous solution with submicromolar binding affinities as determined by ELISA and quartz crystal microbalance with dissipation monitoring (QCM-D), through a process largely dominated by electrostatic interactions. Atomic force microscopy (AFM) reveals a densely packed peptide adlayer with an average height of ~0.5 nm. Subsequently, a PEGylated analogue of the peptide was shown to rapidly coat Ti to afford a nonfouling surface that efficiently blocked the adsorption of fibronectin and significantly reduced the extent of Staphylococcus aureus attachment and biofilm formation in vitro. These PEGylated-peptide coatings show promise in terms of resolving two major hurdles common to implanted metals: (i) nonspecific protein adsorption and (ii) bacterial colonization. At the same time, the facile one-step modification process will facilitate the point-of-care application of these coatings in the surgical suite.
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