MECHANISM OF ACUTE INFLAMMATORY RESPONSE TO BIOMATERIALS

Despite the non-toxic and unreactive nature of polymeric compounds employed in biomaterials, implants made of these materials often trigger inflammatory reactions, likely initiated by the spontaneous adsorption of a layer of host protein to the material surface. Material coated with albumin may be ''passivated'' and unlikely to trigger either thrombogenic or inflammatory responses whereas implants preincubated with plasma may attract large number of phagocytes. In an effort to understand the basis of inflammatory responses to biomaterials, we have employed implants made of polyester terephthalate. This review briefly summarizes our recent progress in determining the importance of adsorbed proteins in the attraction of phagocytic cells to device surfaces. Our initial hypothesis was that spontaneous adsorption of immunoglobulin G (IgG) was critical in later inflammatory reactions. Although samples of Mylar film, preincubated with purified IgG and implanted in mice did, as expected, prompt the accumulation of large numbers of phagocytes shortly after implantation, so also did uncoated material implanted in severely hypogammaglobulinemic mice (with severe combined immune-deficiency), implying that surface adsorption of IgG was not a necessary precedent to phagocyte responses. However, we subsequently observed that material preincubated with plasma promoted phagocyte recruitment whereas implants pre-coated with serum did not. The critical plasma component is evidently fibrinogen; not only does fibrinogen coated material attract phagocytes but uncoated material implanted in hypofibrinogen-emic mice fails to elicit an inflammatory response (unless pre-coated with fibrinogen). This pro-inflammatory effect of adsorbed fibrinogen suggests an interesting connection between two of the major iatrogenic effects of implanted and blood contact biomaterials: thrombosis and inflammation.