Protein-mediated macrophage adhesion and activation on biomaterials: a model for modulating cell behavior

The elucidation of proteins involved in biomaterial-modulated macrophage be havior is critical for the improvement of material performance and the init ial exploration of material design capable of manipulating macrophage funct ion for tissue engineering. In this paper, several in vitro and in vivo tec hniques are presented to demonstrate means of delineating a part of the com plex molecular mechanisms involved in the interaction between biomaterial a nd macrophage adhesion and phenotypic development. The following conclusion s were reached: (1) using radioimmunoassay, complement component C3 was fou nd to be critical in mediating human macrophage adhesion on polyurethanes. (2) The presence of a diphenolic antioxidant additive in polyurethanes incr eased the propensity for complement upregulation but did not affect adheren t macrophage density. (3) The subcutaneous cage-implant system was utilized to delineate interleukin-4 participation in the fusion of adherent macroph ages to form foreign body giant cells in vivo in mice. The injection of pur ified interleukin-4 neutralizing antibody into the implanted cages signific antly decreased the giant cell density; conversely, the giant cell density was significantly increased by the injection of recombinant interleukin-4 w hen compared with the controls. (4) The RGD and PHSRN amino acid sequences of the central cell binding domain and the PRRARV sequence of the C-termina l heparin binding domain of human plasma fibronectin were utilized to study the structure-functional relationship of protein in mediating macrophage b ehavior. Polyethyleneglycol-based networks grafted with the RGD-containing peptide supported higher adherent human macrophage density than surfaces gr afted with other peptides. The formation of foreign body giant cell was hig hly dependent on the relative orientation between PHSRN and RGD domains loc ated in a single peptide. (C) 1999 Kluwer Academic Publishers.