FIBRIN(OGEN) MEDIATES ACUTE INFLAMMATORY RESPONSES TO BIOMATERIALS

Although ''biocompatible'' polymeric elastomers are generally nontoxic , nonimmunogenic, and chemically inert, implants made of these materia ls may trigger acute and chronic inflammatory responses. Early interac tions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the imp ortance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were im planted intraperitoneally for short periods. Material preincubated wit h albumin is ''passivated,'' accumulating very few adherent neutrophil s or macrophages, whereas uncoated or plasma-coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumul ation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption o f fibrinogen appears to be critical: (a) PET coated with serum or hypo fibrinogenemic plasma attracts as few phagocytes as does albumin-coate d material; (b) in contrast, PET preincubated with serum or hypofibrin ogenemic plasma containing physiologic amounts of fibrinogen elicits ' 'normal'' phagocyte recruitment; (c) most importantly, hypofibrinogene mic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected wi th fibrinogen before implantation. Thus, spontaneous adsorption of fib rinogen appears to initiate the acute inflammatory response to an impl anted polymer, suggesting an interesting nexus between two major iatro genic effects of biomaterials: clotting and inflammation.