Biomaterials and Granulomas

Abstract

The rapidly expanding use of implants for reconstruction and repair of diseased or traumatized tissues and organs has fueled the search for biomaterials that are stable, nontoxic, and biologically inert. Unfortunately, implants frequently cause acute or chronic inflammation resulting in tissue damage and rejection. Inflammation usually occurs at the biomaterial–tissue interface and reflects surface adsorption of plasma proteins, complement activation, neutrophil and macrophage infiltration, hyperplasia, and release of inflammatory mediators and proteolytic enzymes. If the biomaterial degrades, either spontaneously or due to biologic activity, components can leach into surrounding tissues and may enter the circulation, causing toxic effects systemically and in distant sites. Inflammation of connective tissues in genetically susceptible individuals can potentially activate the immune system and break tolerance to tissue-specific antigens. Experimentally induced animal models of arthritis chronicle the evolution of a chronic, destructive inflammation localized to peripheral joints. Models of autoimmune arthritis involve hyperimmunization with heterologous cartilage components, such as type II collagen or proteoglycan, leading to cross-reactivity with self-cartilage. Other apparently nonimmune models, oil-induced arthritis and pristane arthritis, may reflect granuloma formation and uncontrolled cytokine production. The antigen-induced arthritis model, developed by hyperimmunization with a foreign antigen that is subsequently injected into the joint cavity, is ideal for biocompatibility testing of cationic substances that may be immunogenic. This variety of models offers the means to understand adverse implant–tissue interactions and granuloma formation such that safer biomaterials can be developed in the future.