Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials

Abstract

All biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs) are the dominant early responders to biomaterial implantation and remain at biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical and morphological characteristics of biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between biomaterial properties and those that result from interactions with the local environment. By having a better understanding of the role of macrophages in the tissue healing processes, especially in events that follow biomaterial implantation, we can design novel biomaterials-based tissue-engineered constructs that elicit a favorable immune response upon implantation and perform for their intended applications.

Keywords: biomaterials; cell-material interaction; cellular and tissue response; foreign body reaction; implantable materials; macrophages.

Figure 1

The sequence of host reactions upon implantation of biomaterial device in vivo. (a) Surgical incision and implant being placed causing injury; (b) blood-biomaterial interaction upon implantation; (c) inflamed soft tissue; (d) implant enclosed by fibrous capsule.

Figure 2

A schematic depiction of the transition of a blood-circulating monocyte to biomaterial/tissue interface-adherent monocyte/macrophage to foreign body giant cell.

Figure 3

Immediately after implantation in vivo, a layer of proteins from the microenvironment adsorb and coat the surface of the biomaterial device. This protein adsorption results in attraction, infiltration, and attachment of various cell types such as monocytes, macrophages, and platelets. These cell types release chemokines and cytokines that recruit tissue repair cells to the site of inflammation. These cells produce collagen and result in the fibrous encapsulation of the implanted material.

Figure 4

(a) Mixed acute and chronic inflammatory infiltrate; (b,c) FBGCs surrounding a foreign body; (d) Fibrous tissue and FBGC.

Figure 5

A schematic depiction of macrophage response to biomaterials depending on the size of the implanted materials. Macrophages respond to small fragments and particles (<10 μm in diameter) by internalization via phagocytosis and intracellular digestion. If the particle size is larger than 10 μm and smaller than 100 μm, the macrophages fuse together, forming giant cells which in turn engulf the particles and digest them. If the particles are larger, the bulk digestion is carried out via extracellular degradation by macrophages and macrophage-fused giant cells through the release of enzymes and/or pH lowering mechanisms.