Molecular basis of biomaterial-mediated foreign body reactions

• Published in: Blood Vol. 98; no. 4; pp. 1231 - 1238
• Main Authors: Hu, Wen-Jing, Eaton, John W., Ugarova, Tatiana P., Tang, Liping
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-08-2001; The Americain Society of Hematology
• Subjects: Adsorption; Animals; Binding Sites; Biocompatible Materials - adverse effects; Biocompatible Materials - metabolism; Biological and medical sciences; Cell Adhesion; Epitopes; Fibrin - metabolism; Fibrinogen - metabolism; Foreign-Body Reaction - etiology; Fundamental and applied biological sciences. Psychology; Humans; Inflammation; Inflammation - etiology; Macrophage-1 Antigen - metabolism; Male; Medical sciences; Mice; Models, Animal; Molecular and cellular biology; Phagocytes - chemistry; Phagocytes - physiology; Polyethylene Terephthalates - adverse effects; Polyethylene Terephthalates - metabolism; Protein Binding; Protein Structure, Tertiary; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Thrombin - pharmacology; Human; Blood coagulation; Antigenic determinant; Implant; Pathogenesis; Cell adhesion molecule; Inflammation; Integrin; Fibrinogen; Fibrosis; Complication; Biomaterial; Foreign body; Phagocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.4.1231

Despite being inert and nontoxic, implanted biomaterials often trigger adverse foreign body reactions such as inflammation, fibrosis, infection, and thrombosis. With regard to the inflammatory responses to biomaterial implants, it was previously found that a crucial precedent event was the spontaneous adsorption and denaturation of fibrinogen on implant surfaces. It was further found that interactions between the phagocyte integrin Mac-1 (CD11b/CD18) and one short sequence within the fibrinogen D domain (γ190-202; P1) at least partially explained phagocyte accumulation on implant surfaces. However, the reason that adsorbed fibrinogen is proinflammatory—while soluble fibrinogen clearly is not—remained obscure. In this study, therefore, the question of how fibrinogen is converted to a proinflammatory state when adsorbed to biomaterial surfaces is investigated. In soluble fibrinogen, the 13 amino acid P1 sequence was found to be hidden. However, the adsorption and denaturation of fibrinogen on the surfaces of commonly used biomaterials lead to the exposure of P1 and a second neo-epitope, γ377-395 (P2), which also interacts with Mac-1 and is similarly occult in the soluble protein. The extent of biomaterial-mediated P1 and P2 exposure appears directly related to the severity of inflammatory responses to a test panel of biomaterials. Finally, thrombin-mediated conversion of fibrinogen to fibrin also exposes both P1 and P2 epitopes. These observations may help explain both the inflammation caused by many types of implanted biomaterials and that which occurs naturally following thrombotic events.