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The role of Toll-like receptor signaling in the macrophage response to implanted materials

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Abstract

Inflammation is facilitated largely by macrophages and other white blood cells, which recognize and respond to evolutionarily conserved damage-associated molecular patterns that are released upon tissue injury and cell stress. Damage-associated molecular patterns are known to bind Toll-like receptors (TLRs) and initiate inflammatory responses through MyD88-dependent NF-KB signaling. Biomaterial implantation activates the innate immune system, resulting in a chronic inflammatory response known as a foreign body reaction (FBR). In this review, the authors discuss the current understanding of damage-initiated TLR signaling in the FBR and the significance of this response in the success of implanted devices.

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References

  1. J.M. Anderson, A. Rodriguez, and D.T. Chang: Foreign body reaction to biomaterials. Semin. Immunol. 20, 86 (2008).

    CAS  Google Scholar 

  2. J.E. Babensee: Interaction of dendritic cells with biomaterials. Semin. Immunol. 20, 101 (2008).

    CAS  Google Scholar 

  3. D.T. Luttikhuizen, M.J. Van Amerongen, P.C. De Feijter, A.H. Petersen, M.C. Harmsen, and M.J.A. Van Luyn: The correlation between difference in foreign body reaction between implant locations and cytokine and MMP expression. Biomaterials 27, 5763 (2006).

    CAS  Google Scholar 

  4. L.A. McKiel and L.E. Fitzpatrick: Toll-like receptor 2-dependent NF-?B/AP-1 activation by damage-associated molecular patterns adsorbed on polymeric surfaces. ACS Biomater. Sci. Eng. 4, 3792 (2018).

    CAS  Google Scholar 

  5. A.K. Blakney, M.D. Swartzlander, and S.J. Bryant: The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly(ethylene glycol)-based hydrogels. J. Biomed. Mater. Res. A 100, 1375 (2012).

    Google Scholar 

  6. S. Chen, J.A. Jones, Y. Xu, H.-Y. Low, J.M. Anderson, and K.W. Leong: Characterization of topographical effects on macrophage behavior in a foreign body response model. Biomaterials 31, 3479 (2010).

    CAS  Google Scholar 

  7. A. Gessner, A. Lieske, B. Paulke, and R. Müller: Influence of surface charge density on protein adsorption on polymeric nanoparticles: analysis by two-dimensional electrophoresis. Eur. J. Pharm. Biopharm. 54, 165 (2002).

    CAS  Google Scholar 

  8. O. Veiseh, J.C. Doloff, M. Ma, A.J. Vegas, H.H. Tam, A.R. Bader, J. Li, E. Langan, J. Wyckoff, W.S. Loo, S. Jhunjhunwala, A. Chiu, S. Siebert, K. Tang, J. Hollister-Lock, S. Aresta-Dasilva, M. Bochenek, J. Mendoza-Elias, Y. Wang, M. Qi, D.M. Lavin, M. Chen, N. Dholakia, R. Thakrar, I. Lacík, G.C. Weir, J. Oberholzer, D.L. Greiner, R. Langer, and D.G. Anderson: Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14, 643 (2015).

    CAS  Google Scholar 

  9. S.M. Slack, J.L. Bohnert, and T.A. Horbett: The effects of surface chemistry and coagulation factors on fibrinogen adsorption from plasma. Ann. N. Y. Acad. Sci. 516, 223 (1987).

    CAS  Google Scholar 

  10. D.A. Norris, R.A. Clark, L.M. Swigart, J.C. Huff, W.L. Weston, and S.E. Howell: Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes. J. Immunol. 129, 1612 (1982).

    CAS  Google Scholar 

  11. J. Zhou, Y.-T. Tsai, H. Weng, D.W. Baker, and L. Tang: Real time monitoring of biomaterial-mediated inflammatory responses via macrophage-targeting NIR nanoprobes. Biomaterials 32, 9383 (2011).

    CAS  Google Scholar 

  12. T.L. Bonfield, E. Colton, R.E. Marchant, and J.M. Anderson: Cytokine and growth factor production by monocytes/macrophages on protein preadsorbed polymers. J. Biomed. Mater. Res. 26, 837 (1992).

    CAS  Google Scholar 

  13. S.J. Leibovich and R. Ross: The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am. J. Pathol. 78, 71 (1975).

    CAS  Google Scholar 

  14. J.C. Doloff, O. Veiseh, A.J. Vegas, H.H. Tam, S. Farah, M. Ma, J. Li, A. Bader, A. Chiu, A. Sadraei, S. Aresta-Dasilva, M. Griffin, S. Jhunjhunwala, M. Webber, S. Siebert, K. Tang, M. Chen, E. Langan, N. Dholokia, R. Thakrar, M. Qi, J. Oberholzer, D.L. Greiner, R. Langer, and D.G. Anderson: Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat. Mater. 16, 671 (2017).

    CAS  Google Scholar 

  15. G.J. Cannon and J.A. Swanson: The macrophage capacity for phagocytosis. J. Cell Sci. 101, 907 (1992).

    Google Scholar 

  16. T.L. Bonfield, E. Colton, and J.M. Anderson: Plasma protein adsorbed biomedical polymers: activation of human monocytes and induction of interleukin 1. J. Biomed. Mater. Res. 23, 535 (1989).

    CAS  Google Scholar 

  17. T.O. Collier and J.M. Anderson: Protein and surface effects on monocyte and macrophage adhesion, maturation, and survival. J. Biomed. Mater. Res. 60, 487 (2002).

    CAS  Google Scholar 

  18. Q. Zhao, N. Topham, J.M. Anderson, A. Hiltner, G. Lodoen, and C.R. Payet: Foreign-body giant cells and polyurethane biostability: in vivo correlation of cell adhesion and surface cracking. J. Biomed. Mater. Res. 25, 177 (1991).

    CAS  Google Scholar 

  19. H. Kreipe, H.J. Radzun, P. Rudolph, J. Barth, M.L. Hansmann, K. Heidorn, and M.R. Parwaresch: Multinucleated giant cells generated in vitro. Terminally differentiated macrophages with down-regulated c-fms expression. Am. J. Pathol. 130, 232 (1988).

    CAS  Google Scholar 

  20. S. MacLauchlan, E.A. Skokos, N. Meznarich, D.H. Zhu, S. Raoof, J.M. Shipley, R.M. Senior, P. Bornstein, and T.R. Kyriakides: Macrophage fusion, giant cell formation, and the foreign body response require matrix metalloproteinase 9. J. Leukoc. Biol. 85, 617 (2009).

    CAS  Google Scholar 

  21. J.R. Hauzenberger, B.R. Hipszer, C. Loeum, P.A. McCue, M. DeStefano, M.C. Torjman, M.T. Kaner, A.R. Dinesen, I. Chervoneva, T.R. Pieber, and J.I. Joseph: Detailed analysis of insulin absorption variability and the tissue response to continuous subcutaneous insulin infusion catheter implantation in Swine. Diabetes Technol. Ther. 19, 641 (2017).

    CAS  Google Scholar 

  22. J.R. Hauzenberger, J. Münzker, P. Kotzbeck, M. Asslaber, V. Bubalo, J.I. Joseph, and T.R. Pieber: Systematic in vivo evaluation of the time-dependent inflammatory response to steel and Teflon insulin infusion catheters. Sci. Rep. 8, 1132 (2018).

    Google Scholar 

  23. J.C. Pickup, N. Yemane, A. Brackenridge, and S. Pender: Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey. Diabetes Technol. Ther. 16, 145 (2014).

    CAS  Google Scholar 

  24. K. Sutherland, J.R. Mahoney2nd, A.J. Coury, and J.W. Eaton: Degradation of biomaterials by phagocyte-derived oxidants. J. Clin. Invest. 92, 2360 (1993).

    CAS  Google Scholar 

  25. G.J. Picha, J.A. Goldstein, and E. Stohr: Natural-Y Même polyurethane versus smooth silicone: analysis of the soft-tissue interaction from 3 days to 1 year in the rat animal model. Plast. Reconstr. Surg. 85, 903 (1990).

    CAS  Google Scholar 

  26. M.J. Wiggins, B. Wilkoff, J.M. Anderson, and A. Hiltner: Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads. J. Biomed. Mater. Res. 58, 302 (2001).

    CAS  Google Scholar 

  27. J.M. Anderson and K.M. Miller: Biomaterial biocompatibility and the macrophage. Biomaterials 5, 21 (1984).

    Google Scholar 

  28. L.D. Amer, L.S. Saleh, C. Walker, S. Thomas, W.J. Janssen, S. Alper, and S.J. Bryant: Inflammation via myeloid differentiation primary response gene 88 signaling mediates the fibrotic response to implantable synthetic poly(ethylene glycol) hydrogels. Acta Biomater. 100, 105 (2019).

    CAS  Google Scholar 

  29. J. Brash and P. ten Hove: Effect of plasma dilution on adsorption of fibrinogen to solid surfaces. Thromb. Haemost. 51, 326 (1984).

    CAS  Google Scholar 

  30. J.E. Ellingsen: A study on the mechanism of protein adsorption to TiO2. Biomaterials 12, 593 (1991).

    CAS  Google Scholar 

  31. T.A. Horbett: Mass action effects on competitive adsorption of fibrinogen from hemoglobin solutions and from plasma. Thromb. Haemost. 51, 174 (1984).

    CAS  Google Scholar 

  32. T.A. Horbett, P.K. Weathersby, and A.S. Hoffman: The preferential adsorption of hemoglobin to polyethylene. J. Bioeng. 1, 61 (1977).

    CAS  Google Scholar 

  33. P. Roach, D. Farrar, and C.C. Perry: Interpretation of protein adsorption: surface-induced conformational changes. J. Am. Chem. Soc. 127, 8168 (2005).

    CAS  Google Scholar 

  34. T. Undin, S.B. Lind, and A.P. Dahlin: MS for investigation of time-dependent protein adsorption on surfaces in complex biological samples. Future Sci. OA 1, FSO32 (2015).

    Google Scholar 

  35. P. Wojciechowski, P. Ten Hove, and J.L. Brash: Phenomenology and mechanism of the transient adsorption of fibrinogen from plasma (Vroman effect). J. Colloid Interface Sci. 111, 455 (1986).

    CAS  Google Scholar 

  36. M.C. Vyner and B.G. Amsden: Polymer chain flexibility-induced differences in fetuin A adsorption and its implications on cell attachment and proliferation. Acta Biomater. 31, 89 (2016).

    CAS  Google Scholar 

  37. L.E. Fitzpatrick, J.W.Y. Chan, and M.V. Sefton: On the mechanism of poly(methacrylic acid–co–methyl methacrylate)-induced angiogenesis: gene expression analysis of dTHP-1 cells. Biomaterials 32, 8957 (2011).

    CAS  Google Scholar 

  38. V. Milleret, S. Buzzi, P. Gehrig, A. Ziogas, J. Grossmann, K. Schilcher, A.S. Zinkernagel, A. Zucker, and M. Ehrbar: Protein adsorption steers blood contact activation on engineered cobalt chromium alloy oxide layers. Acta Biomater. 24, 343 (2015).

    CAS  Google Scholar 

  39. L.A. Wells, H. Guo, A. Emili, and M.V. Sefton: The profile of adsorbed plasma and serum proteins on methacrylic acid copolymer beads: effect on complement activation. Biomaterials 118, 74 (2017).

    CAS  Google Scholar 

  40. J.D. Andrade and V. Hlady: Plasma protein adsorption: the big twelve. Ann. N. Y. Acad. Sci. 516, 158 (1987).

    CAS  Google Scholar 

  41. D.C. Martin, J.L. Semple, and M.V. Sefton: Poly(methacrylic acid-co-methyl methacrylate) beads promote vascularization and wound repair in diabetic mice. J. Biomed. Mater. Res. A 93A, 484 (2009).

    Google Scholar 

  42. M.D. Swartzlander, C.A. Barnes, A.K. Blakney, J.L. Kaar, T.R. Kyriakides, and S.J. Bryant: Linking the foreign body response and protein adsorption to PEG-based hydrogels using proteomics. Biomaterials 41, 26 (2015).

    CAS  Google Scholar 

  43. J. Andersson, K.N. Ekdahl, R. Larsson, U.R. Nilsson, and B. Nilsson: C3 adsorbed to a polymer surface can form an initiating alternative pathway convertase. J. Immunol. 168, 5786 (2002).

    CAS  Google Scholar 

  44. C.A. Gleissner, I. Shaked, K.M. Little, and K. Ley: CXC chemokine ligand 4 induces a unique transcriptome in monocyte-derived macrophages. J. Immunol. 184, 4810 (2010).

    CAS  Google Scholar 

  45. D.Y. Tzeng, T.F. Deuel, J.S. Huang, and R.L. Baehner: Platelet-derived growth factor promotes human peripheral monocyte activation. Blood 66, 179 (1985).

    CAS  Google Scholar 

  46. G. Broughton, J.E. Janis, and C.E. Attinger: The basic science of wound healing. Plast. Reconstr. Surg. 117, 12S (2006).

    CAS  Google Scholar 

  47. J.P. Edwards, X. Zhang, K.A. Frauwirth, and D.M. Mosser: Biochemical and functional characterization of three activated macrophage populations. J. Leukoc. Biol. 80, 1298 (2006).

    CAS  Google Scholar 

  48. T.J. Mariani, S. Sandefur, J.D. Roby, and R.A. Pierce: Collagenase-3 induction in rat lung fibroblasts requires the combined effects of tumor necrosis factor-alpha and 12-lipoxygenase metabolites: a model of macrophage-induced, fibroblast-driven extracellular matrix remodeling during inflammatory lung injury. Mol. Biol. Cell 9, 1411 (1998).

    CAS  Google Scholar 

  49. C. Wiegand, U. Schönfelder, M. Abel, P. Ruth, M. Kaatz, and U.-C. Hipler: Protease and pro-inflammatory cytokine concentrations are elevated in chronic compared to acute wounds and can be modulated by collagen type I in vitro. Arch. Dermatol. Res. 302, 419 (2010).

    CAS  Google Scholar 

  50. M.J. Flick, X. Du, D.P. Witte, M. Jirousková, D.A. Soloviev, S.J. Busuttil, E.F. Plow, and J.L. Degen: Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J. Clin. Invest. 113, 1596 (2004).

    CAS  Google Scholar 

  51. M. Kovacsovics-Bankowski, K. Clark, B. Benacerraf, and K.L. Rock: Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc. Natl. Acad. Sci. USA 90, 4942 (1993).

    CAS  Google Scholar 

  52. N.J. Hallab, K. McAllister, M. Brady, and M. Jarman-Smith: Macrophage reactivity to different polymers demonstrates particle size- and material-specific reactivity: PEEK-OPTIMA® particles versus UHMWPE particles in the submicron, micron, and 10 micron size ranges. J. Biomed. Mater. Res. B Appl. Biomater. 100B, 480 (2012).

    CAS  Google Scholar 

  53. W.G. Brodbeck, J. Patel, G. Voskerician, E. Christenson, M.S. Shive, Y. Nakayama, T. Matsuda, N.P. Ziats, and J.M. Anderson: Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo. Proc. Natl. Acad. Sci. USA 99, 10287 (2002).

    CAS  Google Scholar 

  54. M. Stein, S. Keshav, N. Harris, and S. Gordon: Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J. Exp. Med. 176, 287 (1992).

    CAS  Google Scholar 

  55. J.M. Anderson: Inflammation, wound healing, and the foreign body response. In Biomaterials Science: An Introduction to Materials in Medicine, edited by B. Ratner, A. Hoffman, F. Schoen, and J. Lemons (Elsevier, New York, 2004), p. 296.

    Google Scholar 

  56. A.K. Mcnally, K.M. Defife, and J.M. Anderson: Interleukin-4-induced macrophage fusion is prevented by inhibitors of mannose receptor activity. Am. J. Pathol. 149, 975 (1996).

    CAS  Google Scholar 

  57. A.K. McNally, J.A. Jones, S.R. MacEwan, E. Colton, and J.M. Anderson: Vitronectin is a critical protein adhesion substrate for IL-4-induced foreign body giant cell formation. J. Biomed. Mater. Res. A 86A, 535 (2008).

    CAS  Google Scholar 

  58. A.K. McNally and J.M. Anderson: ß1 and ß2 integrins mediate adhesion during macrophage fusion and multinucleated foreign body giant cell formation. Am. J. Pathol. 160, 621 (2002).

    CAS  Google Scholar 

  59. W.G. Brodbeck, Y. Nakayama, T. Matsuda, E. Colton, N.P. Ziats, and J.M. Anderson: Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro. Cytokine 18, 311 (2002).

    CAS  Google Scholar 

  60. R. Sridharan, A.R. Cameron, D.J. Kelly, C.J. Kearney, and F.J. O’Brien: Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Mater. Today 18, 313 (2015).

    CAS  Google Scholar 

  61. Y. Onuki, U. Bhardwaj, F. Papadimitrakopoulos, and D.J. Burgess: A review of the biocompatibility of implantable devices: current challenges to overcome foreign body response. J. Diabetes Sci. Technol. 2, 1003 (2008).

    Google Scholar 

  62. F.A.W. Verreck, T. de Boer, D.M.L. Langenberg, M.A. Hoeve, M. Kramer, E. Vaisberg, R. Kastelein, A. Kolk, R. de Waal-Malefyt, and T.H.M. Ottenhoff: Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc. Natl. Acad. Sci. USA 101, 4560 (2004).

    CAS  Google Scholar 

  63. D. Bosisio, N. Polentarutti, M. Sironi, S. Bernasconi, K. Miyake, G.R. Webb, M.U. Martin, A. Mantovani, and M. Muzio: Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-?: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood 99, 3427 (2002).

    CAS  Google Scholar 

  64. P.C.S. Bota, A.M.B. Collie, P. Puolakkainen, R.B. Vernon, E.H. Sage, B.D. Ratner, and P.S. Stayton: Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro. J. Biomed. Mater. Res. A 95, 649 (2010).

    Google Scholar 

  65. K. Deonarine, M.C. Panelli, M.E. Stashower, P. Jin, K. Smith, H.B. Slade, C. Norwood, E. Wang, F.M. Marincola, and D.F. Stroncek: Gene expression profiling of cutaneous wound healing. J. Transl. Med. 5, 11 (2007).

    Google Scholar 

  66. L.R. Madden, D.J. Mortisen, E.M. Sussman, S.K. Dupras, J.A. Fugate, J.L. Cuy, K.D. Hauch, M.A. Laflamme, C.E. Murry, and B.D. Ratner: Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc. Natl. Acad. Sci. USA 107, 15211 (2010).

    CAS  Google Scholar 

  67. M. Modolell, I.M. Corraliza, F. Link, G. Soler, and K. Eichmann: Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH 1 and TH 2 cytokines. Eur. J. Immunol. 25, 1101 (1995).

    CAS  Google Scholar 

  68. D.V. Krysko, P. Agostinis, O. Krysko, A.D. Garg, C. Bachert, B.N. Lambrecht, and P. Vandenabeele: Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol. 32, 157 (2011).

    CAS  Google Scholar 

  69. S.T. Smiley, J.A. King, and W.W. Hancock: Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J. Immunol. 167, 2887 (2001).

    CAS  Google Scholar 

  70. K. Ohashi, V. Burkart, S. Flohe, and H. Kolb: Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 164, 558 (2000).

    CAS  Google Scholar 

  71. P.D. Stahl, R. Alan, and B. Ezekowitzt: The mannose receptor is a pattern recognition receptor involved in host defense. Curr. Opin. Immunol. 10, 50 (1998).

    CAS  Google Scholar 

  72. L. Peiser, P.J. Gough, T. Kodama, and S. Gordon: Macrophage class A scavenger receptor-mediated phagocytosis of Escherichia coli: role of cell heterogeneity, microbial strain, and culture conditions in vitro. Infect. Immun. 68, 1953 (2000).

    CAS  Google Scholar 

  73. S. Józefowski, M. Arredouani, T. Sulahian, and L. Kobzik: Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO. J. Immunol. 175, 8032 (2005).

    Google Scholar 

  74. H. Wang, L. Wu, and B.M. Reinhard: Scavenger receptor mediated endocytosis of silver nanoparticles into J774A.1 macrophages is heterogeneous. ACS Nano 6, 7122 (2012).

    CAS  Google Scholar 

  75. D.H. Sun, M.C. Trindade, Y. Nakashima, W.J. Maloney, S.B. Goodman, D.J. Schurman, and R.L. Smith: Human serum opsonization of orthopedic biomaterial particles: protein-binding and monocyte/macrophage activation in vitro. J. Biomed. Mater. Res. A 65, 290 (2003).

    Google Scholar 

  76. R.H. Müller, D. Rühl, M. Lück, and B.-R. Paulke: Influence of fluorescent labelling of polystyrene particles on phagocytic uptake, surface hydrophobicity, and plasma protein adsorption. Pharm. Res. 14, 18 (1997).

    Google Scholar 

  77. D.J. Kusner, C.F. Hall, and S. Jackson: Fc? receptor-mediated activation of phospholipase D regulates macrophage phagocytosis of IgG-opsonized particles. J. Immunol. 162, 2266 (1999).

    CAS  Google Scholar 

  78. A. Kemp and M. Turner: The role of opsonins in vacuolar sealing and the ingestion of zymosan by human neutrophils. Immunology 59, 69 (1986).

    CAS  Google Scholar 

  79. S.D. Wright and B.C. Meyer: Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser. J. Exp. Med. 162, 762 (1985).

    CAS  Google Scholar 

  80. P.D. Stahl and R.A. Ezekowitz: The mannose receptor is a pattern recognition receptor involved in host defense. Curr. Opin. Immunol. 10, 50 (1998).

    CAS  Google Scholar 

  81. M.G. Netea, C.A. Nold-Petry, M.F. Nold, L.A.B. Joosten, B. Opitz, J.H.M. van der Meer, F.L. van de Veerdonk, G. Ferwerda, B. Heinhuis, I. Devesa, C.J. Funk, R.J. Mason, B.J. Kullberg, A. Rubartelli, J.W.M. van der Meer, and C.A. Dinarello: Differential requirement for the activation of the inflammasome for processing and release of IL-1ß in monocytes and macrophages. Blood 113, 2324 (2009).

    CAS  Google Scholar 

  82. M.S. Caicedo, R. Desai, K. McAllister, A. Reddy, J.J. Jacobs, and N.J. Hallab: Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. J. Orthop. Res. 27, 847 (2009).

    CAS  Google Scholar 

  83. M.-A. Ferko and I. Catelas: Effects of metal ions on caspase-1 activation and interleukin-1ß release in murine bone marrow-derived macrophages. PLoS One 13, e0199936 (2018).

    Google Scholar 

  84. B. Vandanmagsar, Y.-H. Youm, A. Ravussin, J.E. Galgani, K. Stadler, R.L. Mynatt, E. Ravussin, J.M. Stephens, and V.D. Dixit: The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17, 179 (2011).

    CAS  Google Scholar 

  85. S. Christo, A. Bachhuka, K.R. Diener, K. Vasilev, and J.D. Hayball: The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry. Sci. Rep. 6, 26207 (2016).

    CAS  Google Scholar 

  86. S.N. Christo, K.R. Diener, J. Manavis, M.A. Grimbaldeston, A. Bachhuka, K. Vasilev, and J.D. Hayball: Inflammasome components ASC and AIM2 modulate the acute phase of biomaterial implant-induced foreign body responses. Sci. Rep. 6, 20635 (2016).

    CAS  Google Scholar 

  87. P.R. Solanki, A. Kaushik, A.A. Ansari, G. Sumana, and B. Malhotra: Zinc oxide-chitosan nanobiocomposite for urea sensor. Appl. Phys. Lett. 93, 163903 (2008).

    Google Scholar 

  88. S.R. Jameela, T.V. Kumary, A.V. Lal, and A. Jayakrishnan: Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system. J. Control Release 52, 17 (1998).

    CAS  Google Scholar 

  89. W. Wu, J. Shen, P. Banerjee, and S. Zhou: Chitosan-based responsive hybrid nanogels for integration of optical pH-sensing, tumor cell imaging and controlled drug delivery. Biomaterials 31, 8371 (2010).

    CAS  Google Scholar 

  90. S. Gudmundsdottir, R. Lieder, O.E. Sigurjonsson, and P.H. Petersen: Chitosan leads to downregulation of YKL-40 and inflammasome activation in human macrophages. J. Biomed. Mater. Res. A 103, 2778 (2015).

    CAS  Google Scholar 

  91. C.M. Artlett, S. Sassi-Gaha, J.L. Rieger, A.C. Boesteanu, C.A. Feghali-Bostwick, and P.D. Katsikis: The inflammasome activating caspase 1 mediates fibrosis and myofibroblast differentiation in systemic sclerosis. Arthritis Rheum. 63, 3563 (2011).

    CAS  Google Scholar 

  92. G. Krissansen, M. Elliott, C. Lucas, F. Stomski, M. Berndt, D. Cheresh, A. Lopez, and G. Burns: Identification of a novel integrin beta subunit expressed on cultured monocytes (macrophages). Evidence that one alpha subunit can associate with multiple beta subunits. J. Biol. Chem. 265, 823 (1990).

    CAS  Google Scholar 

  93. J.-L. Guan, J.E. Trevithick, and R. Hynes: Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein. Cell Regul. 2, 951 (1991).

    CAS  Google Scholar 

  94. K. Suehiro, J. Gailit, and E.F. Plow: Fibrinogen is a ligand for integrin a5ß1 on endothelial cells. J. Biol. Chem. 272, 5360 (1997).

    CAS  Google Scholar 

  95. T. Kamata, R. Wright, and Y. Takada: Critical threonine and aspartic acid residues within the I domains of ß2 integrins for interactions with intercellular adhesion molecule 1 (ICAM-1) and C3bi. J. Biol. Chem. 270, 12531 (1995).

    CAS  Google Scholar 

  96. S. Xu, J. Wang, J.-H. Wang, and T.A. Springer: Distinct recognition of complement iC3b by integrins aXß2 and aMß2. Proc. Natl. Acad. Sci. USA 114, 3403 (2017).

    CAS  Google Scholar 

  97. S. Akira, K. Takeda, and T. Kaisho: Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2, 675 (2001).

    CAS  Google Scholar 

  98. M. Triantafilou, F.G. Gamper, R.M. Haston, M.A. Mouratis, S. Morath, T. Hartung, and K. Triantafilou: Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J. Biol. Chem. 281, 31002 (2006).

    CAS  Google Scholar 

  99. S.M. Mäkelä, M. Strengell, T.E. Pietilä, and I. Julkunen: Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells. J. Leukoc. Biol. 85, 664 (2009).

    Google Scholar 

  100. F.A.W. Verreck, T. de Boer, D.M.L. Langenberg, L. van der Zanden, and T.H.M. Ottenhoff: Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-?- and CD40L-mediated costimulation. J. Leukoc. Biol. 79, 285 (2006).

    CAS  Google Scholar 

  101. N. Tanimura, S. Saitoh, F. Matsumoto, S. Akashi-Takamura, and K. Miyake: Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Biochem. Biophys. Res. Commun. 368, 94 (2008).

    CAS  Google Scholar 

  102. T. Kawai, O. Takeuchi, T. Fujita, J.-i. Inoue, P.F. Mühlradt, S. Sato, K. Hoshino, and S. Akira: Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167, 5887 (2001).

    CAS  Google Scholar 

  103. H. Häcker, V. Redecke, B. Blagoev, I. Kratchmarova, L.-C. Hsu, G.G. Wang, M.P. Kamps, E. Raz, H. Wagner, G. Häcker, M. Mann, and M. Karin: Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 439, 204 (2006).

    Google Scholar 

  104. S. Panda, J.A. Nilsson, and N.O. Gekara: Deubiquitinase MYSM1 regulates innate immunity through inactivation of TRAF3 and TRAF6 complexes. Immunity 43, 647 (2015).

    CAS  Google Scholar 

  105. L. Macedo, G. Pinhal-Enfield, V. Alshits, G. Elson, B.N. Cronstein, and S.J. Leibovich: Wound healing is impaired in MyD88-deficient mice a role for MyD88 in the regulation of wound healing by adenosine a 2A receptors. Am. J. Pathol. 171, 1774 (2007).

    CAS  Google Scholar 

  106. M.R. Dasu, R.K. Thangappan, A. Bourgette, L.A. DiPietro, R. Isseroff, and I. Jialal: TLR2 expression and signaling-dependent inflammation impair wound healing in diabetic mice. Lab. Invest. 90, 1628 (2010).

    CAS  Google Scholar 

  107. Q. Lin, D. Fang, J. Fang, X. Ren, X. Yang, F. Wen, and S.B. Su: Impaired wound healing with defective expression of chemokines and recruitment of myeloid cells in TLR3-deficient mice. J. Immunol. 186, 3710 (2011).

    CAS  Google Scholar 

  108. Q. Lin, L. Wang, Y. Lin, X. Liu, X. Ren, S. Wen, X. Du, T. Lu, S.Y. Su, X. Yang, W. Huang, S. Zhou, F. Wen, and S.B. Su: Toll-like receptor 3 ligand polyinosinic: polycytidylic acid promotes wound healing in human and murine skin. J. Invest. Dermatol. 132, 2085 (2012).

    CAS  Google Scholar 

  109. L. Chen, S. Guo, M.J. Ranzer, and L.A. Dipietro: Toll-like receptor 4 has an essential role in early skin wound healing. J. Invest. Dermatol. 133, 258 (2013).

    CAS  Google Scholar 

  110. E. Seki, S. De Minicis, C.H. Österreicher, J. Kluwe, Y. Osawa, D.A. Brenner, and R.F. Schwabe: TLR4 enhances TGF-ß signaling and hepatic fibrosis. Nat. Med. 13, 1324 (2007).

    CAS  Google Scholar 

  111. X. Zhang and D. Mosser: Macrophage activation by endogenous danger signals. J. Pathol. 214, 161 (2008).

    CAS  Google Scholar 

  112. P. Scaffidi, T. Misteli, and M.E. Bianchi: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191 (2002).

    CAS  Google Scholar 

  113. R.M. Vabulas: HSP70 as endogenous stimulus of the toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 277, 15107 (2002).

    CAS  Google Scholar 

  114. K.R. Taylor, J.M. Trowbridge, J.A. Rudisill, C.C. Termeer, J.C. Simon, and R.L. Gallo: Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J. Biol. Chem. 279, 17079 (2004).

    CAS  Google Scholar 

  115. Y. Okamura, M. Watari, E.S. Jerud, D.W. Young, S.T. Ishizaka, J. Rose, J.C. Chow, and J.F. Strauss: The extra domain A of fibronectin activates Toll-like receptor 4. J. Biol. Chem. 276, 10229 (2001).

    CAS  Google Scholar 

  116. D.V. Krysko, A. Kaczmarek, O. Krysko, L. Heyndrickx, J. Woznicki, P. Bogaert, A. Cauwels, N. Takahashi, S. Magez, C. Bachert, and P. Vandenabeele: TLR-2 and TLR-9 are sensors of apoptosis in a mouse model of doxorubicin-induced acute inflammation. Cell Death Differ. 18, 1316 (2011).

    CAS  Google Scholar 

  117. I.E. Dumitriu, P. Baruah, B. Valentinis, R.E. Voll, M. Herrmann, P.P. Nawroth, B. Arnold, M.E. Bianchi, A.A. Manfredi, and P. Rovere-Querini: Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J. Immunol. 174, 7506 (2005).

    CAS  Google Scholar 

  118. I. Tattoli, L.A. Carneiro, M. Jéhanno, J.G. Magalhaes, Y. Shu, D.J. Philpott, D. Arnoult, and S.E. Girardin: NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-?B and JNK pathways by inducing reactive oxygen species production. EMBO Rep. 9, 293 (2008).

    CAS  Google Scholar 

  119. H. Yuita, M. Tsuiji, Y. Tajika, Y. Matsumoto, K. Hirano, N. Suzuki, and T. Irimura: Retardation of removal of radiation-induced apoptotic cells in developing neural tubes in macrophage galactose-type C-type lectin-1-deficient mouse embryos. Glycobiology 15, 1368 (2005).

    CAS  Google Scholar 

  120. T. Bonaldi, F. Talamo, P. Scaffidi, D. Ferrera, A. Porto, A. Bachi, A. Rubartelli, A. Agresti, and M.E. Bianchi: Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 22, 5551 (2003).

    CAS  Google Scholar 

  121. H. Wang, O. Bloom, M. Zhang, J.M. Vishnubhakat, M. Ombrellino, J. Che, A. Frazier, H. Yang, S. Ivanova, L. Borovikova, K.R. Manogue, E. Faist, E. Abraham, J. Andersson, U. Andersson, P.E. Molina, N.N. Abumrad, A. Sama, and K.J. Tracey: HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248 (1999).

    CAS  Google Scholar 

  122. S. Hirsiger, H.P. Simmen, C.M.L. Werner, G.A. Wanner, and D. Rittirsch: Danger signals activating the immune response after trauma. Mediators Inflamm. 2012, 1 (2012).

    Google Scholar 

  123. W.G. Land: The role of damage-associated molecular patterns (DAMPs) in human diseases: Part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine. Sultan Qaboos Univ. Med. J. 15, e157 (2015).

    Google Scholar 

  124. I. Masouris, M. Klein, S. Dyckhoff, B. Angele, H.W. Pfister, and U. Koedel: Inhibition of DAMP signaling as an effective adjunctive treatment strategy in pneumococcal meningitis. J. Neuroinflammation 14, 214 (2017).

    Google Scholar 

  125. P. Lundbäck, L. Klevenvall, L. Ottosson, H. Schierbeck, K. Palmblad, U. Andersson, and H.E. Harris: Anti HMGB1 treatment reduces inflammation in models of experimental autoimmunity. Ann. Rheum. Dis. 71, A79.3 (2012).

    Google Scholar 

  126. P. Kanellakis, A. Agrotis, S. Kyaw, C. Koulis, I. Ahrens, S. Mori, H.K. Takahashi, K. Liu, K. Peter, M. Nishibori, and A. Bobik: High-mobility group box protein 1 neutralization reduces development of diet-induced atherosclerosis in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 31, 313 (2011).

    CAS  Google Scholar 

  127. A.M. Piccinini and K.S. Midwood: DAMPening inflammation by modulating TLR signalling. Mediators Inflamm. 2010, 1 (2010).

    Google Scholar 

  128. K.A. Daly, S. Liu, V. Agrawal, B.N. Brown, S.A. Johnson, C.J. Medberry, and S.F. Badylak: Damage associated molecular patterns within xenogeneic biologic scaffolds and their effects on host remodeling. Biomaterials 33, 91 (2012).

    CAS  Google Scholar 

  129. T.H. Rogers and J.E. Babensee: Altered adherent leukocyte profile on biomaterials in Toll-like receptor 4 deficient mice. Biomaterials 31, 594 (2010).

    CAS  Google Scholar 

  130. B. Shokouhi, C. Coban, V. Hasirci, E. Aydin, A. Dhanasingh, N. Shi, S. Koyama, S. Akira, M. Zenke, and A.S. Sechi: The role of multiple toll-like receptor signalling cascades on interactions between biomedical polymers and dendritic cells. Biomaterials 31, 5759 (2010).

    CAS  Google Scholar 

  131. T. Uto, T. Akagi, K. Yoshinaga, M. Toyama, M. Akashi, and M. Baba: The induction of innate and adaptive immunity by biodegradable poly(?-glutamic acid) nanoparticles via a TLR4 and MyD88 signaling pathway. Biomaterials 32, 5206 (2011).

    CAS  Google Scholar 

  132. J.E. Babensee and A. Paranjpe: Differential levels of dendritic cell maturation on different biomaterials used in combination products. J. Biomed. Mater. Res. A 74, 503 (2005).

    Google Scholar 

  133. S. Vasilijic, D. Savic, S. Vasilev, D. Vucevic, S. Gasic, I. Majstorovic, S. Jankovic, and M. Colic: Dendritic cells acquire tolerogenic properties at the site of sterile granulomatous inflammation. Cell. Immunol. 233, 148 (2005).

    CAS  Google Scholar 

  134. D.K. Fogg, C. Sibon, C. Miled, S. Jung, P. Aucouturier, D.R. Littman, A. Cumano, and F. Geissmann: A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311, 83 (2006).

    CAS  Google Scholar 

  135. P.M. Kou and J.E. Babensee: Macrophage and dendritic cell phenotypic diversity in the context of biomaterials. J. Biomed. Mater. Res. A 96, 239 (2010).

    Google Scholar 

  136. M. Yoshida and J.E. Babensee: Differential effects of agarose and poly(lactic-co-glycolic acid) on dendritic cell maturation. J. Biomed. Mater. Res. A 79A, 393 (2006).

    CAS  Google Scholar 

  137. M. Yoshida, J. Mata, and J.E. Babensee: Effect of poly(lactic-co-glycolic acid) contact on maturation of murine bone marrow-derived dendritic cells. J. Biomed. Mater. Res. A 80A, 7 (2007).

    CAS  Google Scholar 

  138. S. Teoh: Failure of biomaterials: a review. Int. J. Fatigue 22, 825 (2000).

    CAS  Google Scholar 

  139. Y. Wang, S. Vaddiraju, B. Gu, F. Papadimitrakopoulos, and D.J. Burgess: Foreign body reaction to implantable biosensors: effects of tissue trauma and implant size. J. Diabetes Sci. Technol. 9, 966 (2015).

    CAS  Google Scholar 

  140. B.N. Brown and S.F. Badylak: The role of the host immune response in tissue engineering and regenerative medicine. In Principles of Tissue Engineering, edited by R. Lanza, R. Langer, and J. Vacanti(Academic Press, Cambridge, MA, 2014), p. 497.

    Google Scholar 

  141. B. Rolfe, J. Mooney, B. Zhang, S. Jahnke, S.-J. Le, Y.-Q. Chau, Q. Huang, H. Wang, G. Campbell, and J. Campbell: The fibrotic response to implanted biomaterials: implications for tissue engineering. In Regenerative Medicine and Tissue Engineering - Cells and Biomaterials, edited by D. Eberli(Intech Open, London, 2011), p. 551.

    Google Scholar 

  142. J.E. Sanders, D.V. Cassisi, T. Neumann, S.L. Golledge, S.G. Zachariah, B.D. Ratner, and S.D. Bale: Relative influence of polymer fiber diameter and surface charge on fibrous capsule thickness and vessel density for single-fiber implants. J. Biomed. Mater. Res. 65A, 462 (2003).

    CAS  Google Scholar 

  143. V.G. Percival, J. Riddell, and T.B. Corcoran: Single dose dexamethasone for postoperative nausea and vomiting–a matched case-control study of postoperative infection risk. Anaesth. Intensive Care 38, 661 (2010).

    CAS  Google Scholar 

  144. M. Durmus, E. Karaaslan, E. Ozturk, M. Gulec, M. Iraz, N. Edali, and M.O. Ersoy: The effects of single-dose dexamethasone on wound healing in rats. Anesth. Analg. 97, 1377 (2003).

    CAS  Google Scholar 

  145. D. Naber, P. Sand, and B. Heigl: Psychopathological and neuropsychological effects of 8-days’ corticosteroid treatment. A prospective study. Psychoneuroendocrinology 21, 25 (1996).

    CAS  Google Scholar 

  146. S.D. Patil, F. Papadmitrakopoulos, and D.J. Burgess: Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. J. Control. Release 117, 68 (2007).

    CAS  Google Scholar 

  147. L.W. Norton, H.E. Koschwanez, N.A. Wisniewski, B. Klitzman, and W.M. Reichert: Vascular endothelial growth factor and dexamethasone release from nonfouling sensor coatings affect the foreign body response. J. Biomed. Mater. Res. A 81A, 858 (2007).

    CAS  Google Scholar 

  148. M.N. Avula, A.N. Rao, L.D. Mcgill, D.W. Grainger, and F. Solzbacher: Foreign body response to subcutaneous biomaterial implants in a mast cell-deficient Kit w-Sh murine model. Acta Biomater. 10, 1856 (2014).

    CAS  Google Scholar 

  149. C.N. Serhan, C.B. Clish, J. Brannon, S.P. Colgan, N. Chiang, and K. Gronert: Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med. 192, 1197 (2000).

    CAS  Google Scholar 

  150. MarketsAndMarkets.com: Biomaterials Market by Application and Geography — Global Forecast 2021 (Northbrook, IL, 2016).

  151. G. Jiang and D.D. Zhou: Technology advances and challenges in hermetic packaging for implantable medical devices. In Implantable Neural Protheses 2, edited by D.D. Zhou and E. Greenbaum(Springer Science + Business Media, New York City, NY, 2010), p. 27.

    Google Scholar 

  152. T. Thwaites: Total recall for medical implants. New Sci. 145, 12 (1995).

    Google Scholar 

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  1. Department of Chemical Engineering, Queen’s University, Dupuis Hall, Room 201, 19 Division St, Kingston, Ontario, K7K 3N6, Canada

    Laura A. McKiel, Kimberly A. Woodhouse & Lindsay E. Fitzpatrick

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McKiel, L.A., Woodhouse, K.A. & Fitzpatrick, L.E. The role of Toll-like receptor signaling in the macrophage response to implanted materials. MRS Communications 10, 55–68 (2020). https://doi.org/10.1557/mrc.2019.154

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