Controlled Macrophage Adhesion on Micropatterned Hydrogel Surfaces
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Controlled Macrophage Adhesion on Micropatterned Hydrogel Surfaces P. Krsko1, K. Vartanian2, H. Geller2, M. Libera1 Stevens Institute of Technology, Hoboken, NJ 2 NIH NHLBI, Bethesda, MD 1
ABSTRACT We studied the protein adsorption and subsequent macrophage adhesion on poly(ethylene glycol) [PEG] hydrogels crosslinked using a focused electron beam. Thin-film gels were patterned on silicon substrates and could be formed with swell ratios (hydrated height/ dry height) anywhere between fifteen and unity. We have shown that laminin does not adsorb onto highly swelling gels but that it does adsorb on heavily-crosslinked low-swelling gels. As part of ongoing research on patterning surfaces to control neurite growth in the context of the inflammatory environment of a spinal cord injury, we are interested in how these gel surfaces interact with macrophages. We show that the high-swelling PEG gels resist macrophage adhesion, but the macrophages adhere to low-swelling gels pre-exposed to laminin. By spatially patterning combinations of low and high swelling gels, we show that macrophage adhesion can be confined to specific locations on a surface. INTRODUCTION Macrophages play a key role in wound healing and the inflammatory response. Their ability to debride injured tissue by phagocytosis and enzymatic digestion is well known [1,2]. In addition, macrophages secrete a number of growth factors and cytokines that promote fibrosis, neovascularization, and tissue regeneration. Which of these functions prevails is dependent upon specific context of the injury response. Our goal is to use synthetic biomaterials to promote wound healing and axonal regeneration in response to spinal cord injury, a situation in which macrophage actions are often considered impediments to regeneration. In this context, we are trying to manipulate the local properties of PEG gels to control macrophage behavior. Different strategies have been developed to control macrophage adhesion on surfaces [3-5], and bulk hydrogels that are normally repulsive to macrophages have been used as a platform to append signaling oligopeptides to selectively control macrophage adhesion and influence their subsequent expression [6-8]. It has also been shown that macrophages plated on nanopatterned surface responded with increased spreading and adhesion, as well as an increased number of protrusions of the cell membrane and amount of F-actin. Macrophages adhered on nanopatterned surface also showed increased phagocytotic activity [10]. We have previously shown that thin films of dry PEG homopolymer can be converted to a gel by exposure to 10 keV electrons in a field-emission-gun scanning electron microscope (FEGSEM), and the swelling properties can be controlled by the radiative dose [9]. In contrast to methods such as soft lithography and photolithography, which have been used to pattern cellsurface interactions, e-beam patterning enables us to work with both thin-film and bulk hydrogels, and it avoids the possibility of including unreacted monomer or crosslinking a
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