Fibrin(ogen) mediates acute inflammatory responses to biomaterials.
Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils 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 accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation.
Tang
L
L
Division of Experimental Pathology, Albany Medical College, New York 12208.
Eaton
J W
JW
D000721:Ancrod / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism*; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000166:cytology*; D011093:Polyethylene Terephthalates / Q000378:metabolism*
D001672:Biocompatible Materials; D011093:Polyethylene Terephthalates; D005337:Fibrin; D005340:Fibrinogen; D000721:Ancrod