Monocyte, macrophage and foreign body giant cell interactions with molecularly engineered surfaces

To elucidate the mechanisms involved in monocyte/macrophage adhesion and fu sion to form foreign body giant cells on molecularly engineered surfaces, w e have utilized our in vitro culture system to examine surface chemistry ef fects, cytoskeletal reorganization and adhesive structure development, and cell receptor-ligand interactions in in vitro foreign body giant cell forma tion. Utilizing silane-modified surfaces, monocyte/macrophage adhesion was essentially unaffected by surface chemistry, however the density of foreign body giant cells (FBGCs) was correlated with surface carbon content. An ex ception to the surface-independent macrophage adhesion were the alkyl-silan e modified surfaces which exhibited reduced adhesion and FBGC formation. Ut ilizing confocal immunofluorescent techniques, cytoskeletal reorganization and adhesive structure development in in vitro FBGC formation was studied. Podosomes were identified as the adhesive structures in macrophages and FBG Cs based on the presence of characteristic cytoplasmic proteins and F-actin at the ventral cell surface. Focal adhesion kinase (FAK) and focal adhesio ns were not identified as the adhesive structures in macrophages and FBGCs. In studying the effect of preadsorbed proteins on FBGC formation, fibronec tin or vitronectin do not play major roles in initial monocyte/macrophage a dhesion, whereas polystyrene surfaces modified with RGD exhibited significa nt FBGC formation. These studies identify the potential importance of surfa ce chemistry-dependent conformational alterations which may occur in protei ns adsorbed to surfaces and their potential involvement in receptor-ligand interactions. Significantly, preadsorption of alpha(2)-macroglobulin facili tated macrophage fusion and FBGC formation readily on the RGD surface in th e absence of any additional serum proteins. As alpha(2)-macroglobulin recep tors are not found on blood monocytes but are expressed only with macrophag e development, these results point to a potential interaction between adsor bed alpha(2)-macroglobulin and its receptors on macrophages during macropha ge development and fusion. These studies identify important surface independent and dependent effects in foreign body reaction development that may be important in the identific ation of biological design criteria for molecularly engineered surfaces and tissue engineered devices. (C) 1999 Kluwer Academic Publishers.