Biomaterials 25 (2004) 4135–4148 Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(l-lysine)-grafted-poly(ethylene glycol) copolymers L.G. Harris a, *, S. Tosatti b , M. Wieland c , M. Textor b , R.G. Richards a a AO Research Institute, Interface Biology, Clavadelerstrasse, CH7270 Davos Platz, Switzerland b BioInterface Group, Laboratory for Surface Science and Technology, Department of Materials, Swiss Federal Institute of Technology (ETH) Z . urich, CH8952 Schlieren, Switzerland c Institut Straumann AG, CH4437 Waldenburg, Switzerland Received 29 September 2003; accepted 24 November 2003 Abstract Implanted biomaterials are coated immediately with host plasma constituents, including extracellular matrix (ECM); this reaction may be undesirable in some cases. Poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) has been shown to spontaneously adsorb from aqueous solution onto metal oxide surfaces, effectively reducing the degree of non-specific adsorption of blood and ECM proteins, and decreasing the adhesion of fibroblastic and osteoblastic cells to the coated surfaces. Cell adhesion through specific peptide-integrin receptors could be restored on surfaces coated with PLL-g-PEG functionalized with peptides of the RGD (Arg–Asp–Gly) type. To date, no study has examined the effect of surface modifications by PLL-g-PEG-based polymers on bacterial adhesion. The ability of Staphylococcus aureus to adhere to the ECM and plasma proteins deposited on biomaterials is a significant factor in the pathogenesis of medical-device-related infections. This study describes methods for visualizing and quantifying the adhesion of S. aureus to smooth and rough (chemically etched) titanium surfaces without and with monomolecular coatings of PLL-g-PEG, PLL-g-PEG/PEG-RGD and PLL-g-PEG/PEG-R DG: The different surfaces were exposed to S. aureus cultures for 1–24 h and bacteria surface density was evaluated using scanning electron microscopy and fluorescence microscopy. Coating titanium surfaces with any of the three types of copolymers significantly decreased the adhesion of S. aureus to the surfaces by 89–93% for PLL-g-PEG, and 69% for PLL-g-PEG/PEG-RGD. Therefore, surfaces coated with PLL-g-PEG/PEG-RGD have the ability to attach cells such as fibroblasts and osteoblasts while showing reduced S. aureus adhesion, resulting in a selective biointeraction pattern that may be useful for applications in the area of osteosynthesis, orthopaedic and dental implantology. r 2003 Elsevier Ltd. All rights reserved. Keywords: S. aureus; Surfaces; Poly(ethylene glycol); Titanium; Adhesion; RGD 1. Introduction The implantation of a biomaterial into the human body, and the subsequent damage caused to the tissues is known to increase susceptibility to infection [1], and to activate host defences, stimulating the release of inflammatory mediators, including oxygen radicals and lysosomal enzymes [2–4]. Microbial adhesion to surfaces and the formation of a complex biofilm at the interface between a biomaterial and the biological environment are frequent reasons for sustained inflammatory pro- cesses and ultimate failure of biomedical devices such as vascular and urinary catheters, vascular implants, heart valves and prostheses [5]. Initial adhesion of bacteria to biomaterial surfaces is believed to be the critical event in the pathogenesis of foreign body infections [6,7]. Interactions between biomaterial surfaces and bacteria are thought to be based on a variety of forces including electrostatic, Lifshitz–Van der Waals and hydrophobic forces, as well as various specific receptor–ligand interactions [7–9]. In the case of bacteria, the negative charge of most metal biomaterial surfaces at physiological pH is believed to initially repel negatively charged bacteria [10]. This effect is, however limited in time since it is known that surfaces of biomaterial implants become rapidly coated with host plasma constituents, including ARTICLE IN PRESS *Corresponding author. Fax: +41-81-414-22-88. E-mail address: llinos.harris@aofoundation.org (L.G. Harris). 0142-9612/$-see front matter r 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2003.11.033