Foreign body reaction to biomaterials

Abstract

The foreign body reaction composed of macrophages and foreign body giant cells is the end-stage response of the inflammatory and wound healing responses following implantation of a medical device, prosthesis, or biomaterial. A brief, focused overview of events leading to the foreign body reaction is presented. The major focus of this review is on factors that modulate the interaction of macrophages and foreign body giant cells on synthetic surfaces where the chemical, physical, and morphological characteristics of the synthetic surface are considered to play a role in modulating cellular events. These events in the foreign body reaction include protein adsorption, monocyte/macrophage adhesion, macrophage fusion to form foreign body giant cells, consequences of the foreign body response on biomaterials, and cross-talk between macrophages/foreign body giant cells and inflammatory/wound healing cells. Biomaterial surface properties play an important role in modulating the foreign body reaction in the first two to four weeks following implantation of a medical device, even though the foreign body reaction at the tissue/material interface is present for the in vivo lifetime of the medical device. An understanding of the foreign body reaction is important as the foreign body reaction may impact the biocompatibility (safety) of the medical device, prosthesis, or implanted biomaterial and may significantly impact short- and long-term tissue responses with tissue-engineered constructs containing proteins, cells, and other biological components for use in tissue engineering and regenerative medicine. Our perspective has been on the inflammatory and wound healing response to implanted materials, devices, and tissue-engineered constructs. The incorporation of biological components of allogeneic or xenogeneic origin as well as stem cells into tissue-engineered or regenerative approaches opens up a myriad of other challenges. An in depth understanding of how the immune system interacts with these cells and how biomaterials or tissue-engineered constructs influence these interactions may prove pivotal to the safety, biocompatibility, and function of the device or system under consideration.

Figures

Figure 1

Sequence of events involved in inflammatory and wound healing responses leading to foreign body giant cell formation. This shows the potential importance of mast cells in the acute inflammatory phase and Th2 lymphocytes in the transient chronic inflammatory phase with the production of IL-4 and IL-13, which can induce monocyte/macrophage fusion to form foreign body giant cells.

Figure 2

In vivo transition from blood-borne monocyte to biomaterial adherent monocyte/macrophage to foreign body giant cell at the tissue/biomaterial interface. There is ongoing research to elucidate the biological mechanisms that are considered to play important roles in the transition to foreign body giant cell development.

Figure 3

Scanning electron microscopy images of an Elasthane 80A Polyurethane surface from an in vivo cage study showing the morphological progression of the foreign body reaction. The sequence of events at the Polyurethane surface includes (A) monocyte adhesion (0 days), (B) monocyte-to-macrophage development (3 days), (C) ongoing macrophage-macrophage fusion (7 days), and (D) foreign body giant cells (14 days).