PHAGOCYTE-SURFACE INTERACTIONS

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DESCRIPTION: These investigations are aimed at determining the mechanisms responsible for the inflammatory and fibrotic changes often triggered by implanted biomaterials. Although implanted medical devices represent an increasingly important therapeutic modality, little is known of the determinants of biocompatibility. The acute and chronic inflammatory responses to implants involving the early phagocyte recruitment to the implant surface often followed by fibrosis are puzzling in view of the generally inert and non-toxic nature of most implantable materials. The Applicants have recently found that the surface adsorption of fibrin(ogen) is a necessary precedent to the attraction of both macrophages and neutrophils to the surfaces of polymeric implants and, probably to later fibrotic changes. Although the requirement for surface fibrinogen adsorption is now established, the secondary events (e.g., possible modifications of bound fibrin(ogen), possible binding of ancillary proteins which may amplify fibrinogen- dependent inflammatory responses, mechanisms of phagocyte recruitment, binding and activation, and processes responsible for the ultimate occurrence of fibrotic changes remain unclear. Therefore, the first aim of the proposed work is that of identifying novel epitopes of fibrin(ogen) which may appear following the surface adsorption and probably conformational change of this complex protein. They shall then attempt to determine the mechanisms involved in phagocyte adhesion to protein-coated implant surfaces, as well as the effects of such cell: protein:surface interactions on the metabolic and pro-inflammatory activities of adherent phagocytes. Finally, preliminary studies will be carried out on the importance of the primary protein adsorption and early wave of phagocyte accumulation on subsequent implant associated fibrotic changes. It is hoped that a better knowledge of these complex host: implant interactions may improve our present understanding of what constitutes biocompatibility and lead to improvements in the design of biomaterial surfaces.