Topographical control of human macrophages by a regularly microstructured polyvinylidene fluoride surface Nora E. Paul a, * , Claudia Skazik b , Marc Harwardt c , Matthias Bartneck a , Bernd Denecke a , Doris Klee c , Jochen Salber c , Gabriele Zwadlo-Klarwasser a a IZKF Biomat, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany b Department of Dermatology, RWTH Aachen University Hospital, 52074 Aachen, Germany c Institute of Technical and Macromolecular Chemistry of RWTH Aachen and DWI at RWTH Aachen, Pauwelsstrasse 8, 52074 Aachen, Germany article info Article history: Received 17 April 2008 Accepted 9 July 2008 Available online 29 July 2008 Keywords: Microstructure Nanotopography Macrophage Inflammation Cytokine Gene expression abstract In this study we investigated the influence of surface topography on the inflammatory response of human macrophages. We generated different polyvinylidene fluoride (PVDF) surfaces including (i) a smooth surface of PVDF spherulites as a control, (ii) a randomly nanotextured surface with alumina particles, and (iii) a microstructure using laser ablation. The identical chemistry of all PVDF surfaces was demonstrated by X-ray photoelectron spectroscopy. The topography was evaluated by white light interferometry and X-profile analysis. Macrophages were cultured on the different surfaces including lipopolysaccharide (LPS) treatment as an inflammatory activator. Our results demonstrate that the mi- crostructured surface but not the nanotexured significantly affects the activation of primary human macrophages by inducing a specific cytokine and gene expression pattern. This activation resulted in a subtype of macrophages with pro- but also anti-inflammatory properties. Interestingly, the response on the topography differed from that triggered by LPS, pointing to a different activation state of the cells. Our data clearly show that a particular topography induces an inflammatory response. This suggests that the modification of topography could influence the inflammatory potency of a biomaterial and hence could affect the biocompatibility of implants. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction It is well known and accepted that the surface topography of an implanted material exerts a significant influence on the function of cells – a term known as ’topographical control’ (reviewed in [1]). However, only 2% of all implants are made of specially optimized biomaterials and many polymers have a micrometre or sub- micrometre scaled topography by accident due to the production process that could trigger undesired cell responses after implan- tation. In particular, the interaction of inflammatory cells with biomaterial surfaces is believed to affect the biocompatibility of a given biomaterial. Among inflammatory cells macrophages play a key role in the host response to foreign bodies therefore being crucial for de- termining the biocompatibility of an implant [2,3]. Macrophages mediate inflammatory processes especially chronic inflammation, the most frequent adverse effect after implantation. Moreover, macrophages are crucially involved in guiding tissue repair and wound healing [4]. The multiple functions of macrophages mirror their heterogeneity. During inflammation macrophages exhibit two different phenotypes: M1 and M2 macrophages [5–7]. M1 macro- phages are classically activated proinflammatory subtypes induced by lipopolysaccharide (LPS). They secrete proinflammatory cyto- kines like interleukin (IL)-1 and IL-6 as well as chemokines and can be stained with the 27E10 antibody directed against a heterodimer formed of the two calcium-binding proteins S100A8 and S100A9 [8,9]. The term M2 macrophages refers to various subtypes of non- classically activated macrophages [6]. A common feature of M2 macrophages is the release of anti-inflammatory cytokines. The scavenger receptor CD163 is a specific surface marker expressed by M2 cells [10,11]. Because of their important role in the foreign body response macrophages are widely used to study the biocompatibility of implanted materials. Several studies point to the significance of the surface chemistry on the inflammatory response of macrophages in particular on cytokine release [12,13]. The influence of topography, however, is poorly investigated. Using murine macrophage cell lines it was reported that rough titanium surfaces induce the expression of proinflammatory cytokines and chemokines on mRNA as well as on protein level [14,15]. With respect to human * Corresponding author. Tel.: þ49 241 8088377; fax: þ49 241 802413. E-mail address: npaul@ukaachen.de (N.E. Paul). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2008.07.010 Biomaterials 29 (2008) 4056–4064