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. Engineering biomaterial to resist the foreign body reaction The foreign body giant cell formation and the fibrous encapsulation of the implanted device can affect the function of the implanted device and lead to its failure. Reducing the foreign body reaction can promote better device performance and durability. Even though many types of implants cannot completely escape the foreign body reaction, there are many ways to engineer biomaterials to reduce the foreign body reaction. Reducing nonspecific protein adsorption is one important method to prevent fibrous encapsulation of the implant. Modification of physical properties The physical properties of the implant's surface, such as size, shape, topology, and strength, influence protein adsorption and immune cell interactions with the implant. Generally, surface roughness induces greater protein adsorption and triggers greater immune response. Thicker cylindrical implants on the millimeter scale were shown to produce greater fibrous encapsulation. However, there may not be an absolute relationship between the modification of the biomaterial and the associated foreign body response, because some biomaterials intrinsically induce a stronger foreign body response than other biomaterials would. Delivery of anti-inflammatory drugs Implanted biomaterial can be loaded with different drugs to perform anti-inflammatory functions or promote angiogenesis to further integrate the implant with the host. The sustained release of certain anti-inflammatory drugs from the