Directed Assembly of PEGylated-Peptide Coatings for Infection-Resistant Titanium Metal

被引:101
作者
Khoo, Xiaojuan [1 ,2 ]
Hamilton, Paul [3 ]
O'Toole, George A. [4 ]
Snyder, Brian D. [5 ]
Kenan, Daniel J. [6 ]
Grinstaff, Mark W. [1 ,2 ]
机构
[1] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
[2] Boston Univ, Dept Chem, Boston, MA 02215 USA
[3] Affinergy Inc, Durham, NC 27713 USA
[4] Dartmouth Med Sch, Dept Microbiol & Immunol, Hanover, NH 03755 USA
[5] Harvard Univ, Sch Med, Dept Orthoped Surg, Childrens Hosp, Boston, MA 02215 USA
[6] Duke Univ, Med Ctr, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
QUARTZ-CRYSTAL MICROBALANCE; IN-SITU ELLIPSOMETRY; PROTEIN ADSORPTION; POLY(ETHYLENE GLYCOL); SURFACES; BACTERIAL; ADHESION; PHAGE; PEG; FIBRINOGEN;
D O I
10.1021/ja9020827
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 similar to 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.
引用
收藏
页码:10992 / 10997
页数:6
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