Localized Immunosuppressive Environment in the Foreign Body Response to Implanted Biomaterials

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2009 Jun 17

PMID 19528351

Citations 54

Authors

David M Higgins

Randall J Basaraba

April C Hohnbaum

Eric J Lee

David W Grainger

Mercedes Gonzalez-Juarrero

Affiliations

Soon will be listed here.

Abstract

The implantation of synthetic biomaterials initiates the foreign body response (FBR), which is characterized by macrophage infiltration, foreign body giant cell formation, and fibrotic encapsulation of the implant. The FBR is orchestrated by a complex network of immune modulators, including diverse cell types, soluble mediators, and unique cell surface interactions. The specific tissue locations, expression patterns, and spatial distribution of these immune modulators around the site of implantation are not clear. This study describes a model for studying the FBR in vivo and specifically evaluates the spatial relationship of immune modulators. We modified a biomaterials implantation in vivo model that allowed for cross-sectional in situ analysis of the FBR. Immunohistochemical techniques were used to determine the localization of soluble mediators, ie, interleukin (IL)-4, IL-13, IL-10, IL-6, transforming growth factor-beta, tumor necrosis factor-alpha, interferon-gamma, and MCP-1; specific cell types, ie, macrophages, neutrophils, fibroblasts, and lymphocytes; and cell surface markers, ie, F4/80, CD11b, CD11c, and Ly-6C, at early, middle, and late stages of the FBR in subcutaneous implant sites. The cytokines IL-4, IL-13, IL-10, and transforming growth factor-beta were localized to implant-adherent cells that included macrophages and foreign body giant cells. A better understanding of the FBR in vivo will allow the development of novel strategies to enhance biomaterial implant design to achieve better performance and safety of biomedical devices at the site of implant.

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References

Klonoff D . Continuous glucose monitoring: roadmap for 21st century diabetes therapy. Diabetes Care. 2005; 28(5):1231-9. DOI: 10.2337/diacare.28.5.1231. View

Gretzer C, Emanuelsson L, Liljensten E, Thomsen P . The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials. J Biomater Sci Polym Ed. 2006; 17(6):669-87. DOI: 10.1163/156856206777346340. View

Athanasou N, Quinn J . Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistological distinction and implications for osteoclast ontogeny and function. J Clin Pathol. 1990; 43(12):997-1003. PMC: 502972. DOI: 10.1136/jcp.43.12.997. View

Gordon S, Todd J, COHN Z . In vitro synthesis and secretion of lysozyme by mononuclear phagocytes. J Exp Med. 1974; 139(5):1228-48. PMC: 2139654. DOI: 10.1084/jem.139.5.1228. View

Abbondanzo S, Young V, Wei M, Miller F . Silicone gel-filled breast and testicular implant capsules: a histologic and immunophenotypic study. Mod Pathol. 1999; 12(7):706-13. View

Luttikhuizen D, Harmsen M, van Luyn M . Cytokine and chemokine dynamics differ between rats and mice after collagen implantation. J Tissue Eng Regen Med. 2007; 1(5):398-405. DOI: 10.1002/term.50. View

Moore K, de Waal Malefyt R, Coffman R, OGarra A . Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19:683-765. DOI: 10.1146/annurev.immunol.19.1.683. View

Jones J, Chang D, Meyerson H, Colton E, Kwon I, Matsuda T . Proteomic analysis and quantification of cytokines and chemokines from biomaterial surface-adherent macrophages and foreign body giant cells. J Biomed Mater Res A. 2007; 83(3):585-96. DOI: 10.1002/jbm.a.31221. View

Doussis I, Puddle B, Athanasou N . Immunophenotype of multinucleated and mononuclear cells in giant cell lesions of bone and soft tissue. J Clin Pathol. 1992; 45(5):398-404. PMC: 495300. DOI: 10.1136/jcp.45.5.398. View

10.

Brodbeck W, Shive M, Colton E, Ziats N, Anderson J . Interleukin-4 inhibits tumor necrosis factor-alpha-induced and spontaneous apoptosis of biomaterial-adherent macrophages. J Lab Clin Med. 2002; 139(2):90-100. DOI: 10.1067/mlc.2002.121260. View

11.

Darouiche R . Device-associated infections: a macroproblem that starts with microadherence. Clin Infect Dis. 2001; 33(9):1567-72. DOI: 10.1086/323130. View

12.

Gorbet M, Sefton M . Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials. 2004; 25(26):5681-703. DOI: 10.1016/j.biomaterials.2004.01.023. View

13.

Kyriakides T, Foster M, Keeney G, Tsai A, Giachelli C, Clark-Lewis I . The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation. Am J Pathol. 2004; 165(6):2157-66. PMC: 1618731. DOI: 10.1016/S0002-9440(10)63265-8. View

14.

Woerly G, Lacy P, Younes A, Roger N, Loiseau S, Moqbel R . Human eosinophils express and release IL-13 following CD28-dependent activation. J Leukoc Biol. 2002; 72(4):769-79. View

15.

al-Saffar N, Revell P, Kobayashi A . Modulation of the phenotypic and functional properties of phagocytic macrophages by wear particles from orthopaedic implants. J Mater Sci Mater Med. 2004; 8(11):641-8. DOI: 10.1023/a:1018575504518. View

16.

Li A, Quinn M, Siddiqui Y, Wood M, Federiuk I, Duman H . Elevation of transforming growth factor beta (TGFbeta) and its downstream mediators in subcutaneous foreign body capsule tissue. J Biomed Mater Res A. 2007; 82(2):498-508. DOI: 10.1002/jbm.a.31168. View

17.

Higgins D, Sanchez-Campillo J, Rosas-Taraco A, Higgins J, Lee E, Orme I . Relative levels of M-CSF and GM-CSF influence the specific generation of macrophage populations during infection with Mycobacterium tuberculosis. J Immunol. 2008; 180(7):4892-900. DOI: 10.4049/jimmunol.180.7.4892. View

18.

Lim S, Song D, Oh S, Lee-Yoon D, Bae E, Lee J . In vitro and in vivo degradation behavior of acetylated chitosan porous beads. J Biomater Sci Polym Ed. 2008; 19(4):453-66. DOI: 10.1163/156856208783719482. View

19.

Rodriguez A, MacEwan S, Meyerson H, Kirk J, Anderson J . The foreign body reaction in T-cell-deficient mice. J Biomed Mater Res A. 2008; 90(1):106-13. PMC: 3864678. DOI: 10.1002/jbm.a.32050. View

20.

Chang D, Colton E, Anderson J . Paracrine and juxtacrine lymphocyte enhancement of adherent macrophage and foreign body giant cell activation. J Biomed Mater Res A. 2008; 89(2):490-8. PMC: 3864690. DOI: 10.1002/jbm.a.31981. View