Review
Foreign body reaction to biomaterials

https://doi.org/10.1016/j.smim.2007.11.004Get rights and content

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.

Section snippets

Introduction: inflammatory response following material implantation

The perspective of this review originates from our long-standing clinical implant retrieval and evaluation program in the Department of Pathology at the University Hospitals of Cleveland. Simply put, our perspective is derived from surgical pathology and the identification of inflammatory and wound healing responses as opposed to an immunology perspective, which focuses on innate and adaptive immunity. The consistent diagnosis of the foreign body reaction with macrophages and foreign body giant

Adsorption of plasma proteins

Biomaterials and medical devices immediately and spontaneously acquire a layer of host proteins prior to interacting with host cells. Thus, it is highly probable that the types, levels, and surface conformations of the adsorbed proteins are critical determinants of the tissue reaction to such implants [10]. Conversely, the types, concentrations, and conformations of these surface-adsorbed proteins are dependent on biomaterial surface properties that dictate the adhesion and survival of cells,

Macrophage activation and cytokine secretion

Macrophages secrete an array of inflammatory mediators following activation. A resting macrophage becomes activated in response to microbial products, immune complexes, chemical mediators, certain extracellular matrix proteins, and T lymphocyte-derived cytokines. Activated macrophages are capable of secreting a wide range of cytokines such as IL-1, IL-6, IL-10, IL-12, IL-18, TNF-α, TGF-β, IL-8, MCP-1, and MIP-1α/β [101]. Adherent macrophages on biomaterials become activated in an attempt to

Conclusions

The development of novel biomaterials, biomedical devices, or tissue-engineered constructs necessitates a thorough understanding of the biological responses to implanted materials. Once a biomaterial is introduced into the body, a sequence of events occurs in the surrounding tissue and ultimately ends in the formation of foreign body giant cells at the tissue/material interface. The consequences of the reaction to the material surface can be devastating. Our laboratory has focused on gaining a

Acknowledgements

We acknowledge the support from the National Institute of Health and the National Institute of Biomedical Imaging and Bioengineering (EB-000275, EB-000282, and T32 GM07250).

References (157)

  • M.G. Coppolino et al.

    Bi-directional signal transduction by integrin receptors

    Int J Biochem Cell Biol

    (2000)
  • M.H. Lee et al.

    Effect of biomaterial surface properties on fibronectin-alpha5beta1 integrin interaction and cellular attachment

    Biomaterials

    (2006)
  • M.A. Lan et al.

    Myoblast proliferation and differentiation on fibronectin-coated self-assembled monolayers presenting different surface chemistries

    Biomaterials

    (2005)
  • L.T. Allen et al.

    Surface-induced changes in protein adsorption and implications for cellular phenotypic responses to surface interaction

    Biomaterials

    (2006)
  • A.J. Garcia et al.

    Integrin-fibronectin interactions at the cell-material interface: initial integrin binding and signaling

    Biomaterials

    (1999)
  • B.G. Keselowsky et al.

    Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding

    Biomaterials

    (2004)
  • C.H. Damsky et al.

    Integrin signaling: it's where the action is

    Curr Opin Cell Biol

    (2002)
  • S.M. Frisch et al.

    Anoikis mechanisms

    Curr Opin Cell Biol

    (2001)
  • E.H. Chen et al.

    Cell–cell fusion

    FEBS Lett

    (2007)
  • A.K. McNally et al.

    Multinucleated giant cell formation exhibits features of phagocytosis with participation of the endoplasmic reticulum

    Exp Mol Pathol

    (2005)
  • S.M. Jay et al.

    Foreign body giant cell formation is preceded by lamellipodia formation and can be attenuated by inhibition of Rac1 activation

    Am J Pathol

    (2007)
  • A.K. McNally et al.

    Foreign body-type multinucleated giant cell formation is potently induced by alpha-tocopherol and prevented by the diacylglycerol kinase inhibitor R59022

    Am J Pathol

    (2003)
  • W. Cui et al.

    The intracellular domain of CD44 promotes the fusion of macrophages

    Blood

    (2006)
  • X. Han et al.

    CD47, a ligand for the macrophage fusion receptor, participates in macrophage multinucleation

    J Biol Chem

    (2000)
  • A.T. Tsai et al.

    The role of osteopontin in foreign body giant cell formation

    Biomaterials

    (2005)
  • B.G. Keselowsky et al.

    Role of plasma fibronectin in the foreign body response to biomaterials

    Biomaterials

    (2007)
  • Y. Kadoya et al.

    The expression of osteoclast markers on foreign body giant cells

    Bone Miner

    (1994)
  • R.S. Labow et al.

    Hydrolytic degradation of poly(carbonate)-urethanes by monocyte-derived macrophages

    Biomaterials

    (2001)
  • R.S. Labow et al.

    Human macrophage-mediated biodegradation of polyurethanes: assessment of candidate enzyme activities

    Biomaterials

    (2002)
  • R.S. Labow et al.

    The human macrophage response during differentiation and biodegradation on polycarbonate-based polyurethanes: dependence on hard segment chemistry

    Biomaterials

    (2005)
  • J.P. Santerre et al.

    Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials

    Biomaterials

    (2005)
  • J.M. Anderson

    Biological responses to materials

    Annu Rev Mater Res

    (2001)
  • J.M. Anderson

    Multinucleated giant cells

    Curr Opin Hematol

    (2000)
  • C. Gretzer et al.

    The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials

    J Biomater Sci Polym Ed

    (2006)
  • D.T. Luttikhuizen et al.

    Cellular and molecular dynamics in the foreign body reaction

    Tissue Eng

    (2006)
  • T. Horbett

    The role of adsorbed proteins in tissue response to biomaterials

  • J. Zdolsek et al.

    Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    J Transl Med

    (2007)
  • L. Tang et al.

    Mast cells mediate acute inflammatory responses to implanted biomaterials

    Proc Natl Acad Sci U S A

    (1998)
  • A.D. Keegan

    IL-4

  • A.N.J. McKenzie et al.

    IL-13

  • C.J. Wilson et al.

    Mediation of biomaterial-cell interactions by adsorbed proteins: a review

    Tissue Eng

    (2005)
  • C.R. Jenney et al.

    Adsorbed serum proteins responsible for surface dependent human macrophage behavior

    J Biomed Mater Res

    (2000)
  • W.G. Brodbeck et al.

    Effects of adsorbed heat labile serum proteins and fibrinogen on adhesion and apoptosis of monocytes/macrophages on biomaterials

    J Mater Sci Mater Med

    (2003)
  • C.R. Jenney et al.

    Adsorbed IgG: a potent adhesive substrate for human macrophages

    J Biomed Mater Res

    (2000)
  • D.J. Campbell et al.

    Chemokines in the systemic organization of immunity

    Immunol Rev

    (2003)
  • C. Gerard et al.

    Chemokines and disease

    Nat Immunol

    (2001)
  • G. Broughton et al.

    The basic science of wound healing

    Plast Reconstr Surg

    (2006)
  • N.P. Rhodes et al.

    Macrophage subpopulation differentiation by stimulation with biomaterials

    J Biomed Mater Res

    (1997)
  • I.F. Charo et al.

    The many roles of chemokines and chemokine receptors in inflammation

    N Engl J Med

    (2006)
  • J.A. Jones et al.

    Proteomic analysis and quantification of cytokines and chemokines from biomaterial surface-adherent macrophages and foreign body giant cells

    J Biomed Mater Res A

    (2007)
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    All authors contributed equally to the preparation of this review.

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