A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue-encapsulation of an implant is an example, as is inflammation around a splinter. Foreign body granuloma formation consists of protein adsorption, macrophages, multinucleated foreign body giant cells (macrophage fusion), fibroblasts, and angiogenesis. It has also been proposed that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response.
In the long term, the foreign body reaction results in encapsulation of the foreign body within a calcified shell. For example, a lithopedion is a rare phenomenon which occurs most commonly when a fetus dies during an abdominal pregnancy, is too large to be reabsorbed by the body, and calcifies.
Foreign body reaction to biomaterial implantation
Following biomaterial implantation, blood and body fluids contact the implant surface. Host blood proteins adsorb onto the implant surface and a fibrin matrix forms. Acute and chronic inflammation follow the initial blood protein deposition and matrix formation. Macrophages at the implant site fuse to form foreign body giant cells. Following the inflammatory response, granulation tissue form. The end stage of the foreign body reaction is the fibrous capsule formation around the implanted biomaterial. The biocompatibility of the device affects the severity of the foreign body reaction. The foreign body reaction can lead to device failure.
Protein adsorption
During blood-biomaterial interaction, blood proteins spontaneously adsorb to the biomaterial surface. The biomaterial surface properties affect the types, concentrations, and conformation of proteins that adsorb to the surface. The Vroman effect can describe the time-dependent behavior of this protein adsorption. Surface-adsorbed proteins regulate inflammatory cell interaction and adhesion. The deposited proteins allow inflammatory cells to attach via integrins. The biomaterial surface can also recruit and activate complement proteins.
Immune recruitment
The composition and conformation of adsorbed proteins on the implant surface is critical to the foreign body reaction. For the first two days, neutrophils are the primary cell type that deposit on the implant surface. Neutrophils release degradative enzymes and reactive oxygen intermediates that damages the implant. Platelets from the blood-biomaterial interaction release inflammatory cytokines that cause monocytes and macrophages to extravasate and migrate to the implant site. The degranulation and release of histamine from mast cells further recruits macrophages to the biomaterial. Macrophages adhere to the biomaterial surface based on the surface protein deposits and produce cytokines that further recruit macrophages. Foreign body granuloma forms as immune cells accumulate on the biomaterial surface in an attempt to eliminate the biomaterial.
Macrophage fusion
Adherent macrophages at the implant site can fuse into a multinucleated cell called foreign body giant cell. Foreign body giant cell formation depends on the biomaterial surface properties and on the presence of interleukin-4 and interleukin-13. Foreign body giant cells release reactive oxygen intermediates, degradative enzymes, and acid onto the biomaterial surface. Foreign body giant cells also attempt to engulf the biomaterial for degradation. Adherent macrophages and foreign body giant cells degrade biomaterials and can lead to device failure. Foreign body giant cells remain on the surface of the implanted device throughout the device's lifetime.
Fibrous capsule formation
The end-stage healing response is the fibrous encapsulation of the biomaterial. Macrophages and foreign body giant cells release cytokines that attract fibroblasts. Fibroblasts create a collagenous fibrous capsule to separate the biomaterial from the surrounding tissue. The fibrous capsule may hinder the device's function, such as drug diffusion for drug delivery systems or normal tissue regeneration for tissue engineering implants.