MECHANISMS OF FIBRINOGEN DOMAINS - BIOMATERIAL INTERACTIONS

Spontaneous adsorption of fibrinogen is critical to the pathogenesis o f biomaterial-mediated inflammatory responses. However, the mechanism by which adsorbed fibrinogen affects phagocyte responses is still not clear. To investigate the molecular interaction between fibrinogen and biomaterials, fibrinogen fragments (D100 and E50) were generated and used in the present study. The results indicate that biomaterial:D100 interaction is essential to fibrinogen-mediated inflammatory responses , because biomaterials precoated with D100, but not E50, prompt strong inflammatory responses. Furthermore, the results from in vitro studie s show that whole molecule fibrinogen and D100 exhibit very similar pr otein:surface interactions. Specifically: (1) both D100 and fibrinogen have high affinity for biomaterial surfaces; and (2) the retention ra tes of adsorbed D100 in both in vivo and in vitro environments are as high as that for adsorbed fibrinogen. On the other hand, E50 does bind to biomaterials but with low affinity because, once bound, it is not tightly adherent to the biomaterial surfaces. Taken together, the resu lts suggest that the mechanism of fibrinogen mediated inflammatory res ponses may involve the following three consecutive events: (1) after c ontact with blood or tissue fluid, the D domain tends to interact with biomaterial surfaces and is important in the tight binding of fibrino gen to implant surfaces; (2) the biomaterial surface then promotes con formational changes within the D domain, exposing P1 epitope (gamma 19 0-202, which interacts with phaocyte Mac-1 integrin); and (3) the enga gement of Mac-1 integrin with P1 epitope then triggers subsequent phag ocyte adherence and reactions.