title: Implant failure and the immuno-incompetent fibro-inflammatory zone.
abstract: Biomaterial implants are surrounded by an immuno-incompetent, fibro-inflammatory, integration-deficient zone within which stimulation of cellular immune responses results in superoxide radical and cytokine-mediated tissue damage with increased susceptibility to infection or aseptic loosening. Three important questions that pertain to surgical implants are (1) What are the mechanisms that cause abnormal inflammatory responses in the absence of infection and result in interface cellular disorganization and device failure? (2) What causes host defenses to be compromised to the extent that normal flora organisms like Staphylococcus epidermidis, with little or no virulence potential, can cause life-threatening infections at the implant-host interface? (3) What is the nature of surface regions of biomaterials that facilitate bacterial adherence? Pathogenic strains of S. epidermidis and Staphylococcus aureus have an affinity for biomaterial surfaces and are capable of initiating infection. Binding may be nonspecific and glue-like rather than a receptor-ligand event as for S. aureus and matrix proteins. This study indicates bacterial binding to sites of higher vanadium concentration at grain boundaries and mixed phases in titanium alloys. Repeated macrophage priming by biomaterial particulates results in the production of reactive oxygen intermediates, macrophage exhaustion, and adjacent tissue damage. A cytokine cascade is also initiated. A self-perpetuating enlarging immuno-incompetent fibro-inflammatory zone develops about implants, which features tissue cell damage, increased susceptibility to infection, and results in septic or aseptic failure of the implant. These effects are clearly exemplified by fibrosis about breast implants and osteolysis at the interface of total joint replacements.
authors.affiliation: Medical Sciences Research Institute, Herndon, VA 22071.
authors.forename: A G
authors.initials: AG
authors.lastname: Gristina
mesh_terms: D001422:Bacterial Adhesion; D001672:Biocompatible Materials; D006801:Humans; D007121:Immunocompetence; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D010014:Osteolysis / Q000378:metabolism; D019736:Prostheses and Implants; D011475:Prosthesis Failure; D016459:Prosthesis-Related Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000472:pathogenicity; D013212:Staphylococcus epidermidis / Q000472:pathogenicity; D013481:Superoxides / Q000378:metabolism; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D013481:Superoxides