The elucidation of proteins involved in biomaterial-modulated macrophage behavior is crit. for the improvement of material performance and the initial exploration of material design capable of manipulating macrophage function for tissue engineering. Several in vitro and in vivo techniques are presented to demonstrate means of delineating a part of the complex mol. mechanisms involved in the interaction between biomaterial and macrophage adhesion and phenotypic development. RIA showed that complement component C3 was crit. in mediating human macrophage adhesion on polyurethanes. The presence of a diphenolic antioxidant additive in polyurethanes increased the propensity for complement upregulation but did not affect adherent macrophage d. The s.c. cage-implant system was utilized to delineate interleukin-4 participation in the fusion of adherent macrophages to form foreign body giant cells in vivo in mice. Injection of purified interleukin-4-neutralizing antibody into the implanted cages decreased the giant cell d.; conversely, the giant cell d. was increased by injection of recombinant interleukin-4. The RGD and PHSRN amino acid sequences of the central cell-binding domain and the PRRARV sequence of the C-terminal heparin-binding domain of human plasma fibronectin were utilized to study the structure-function relations of proteins in mediating macrophage behavior. PEG-based networks grafted with the RGD-contg. peptide supported higher adherent human macrophage d. than surfaces grafted with other peptides. Formation of foreign body giant cells was highly dependent on the relative orientation between PHSRN and RGD domains located in a single peptide. [on SciFinder (R)]