Skip to main content
SpringerLink
Log in

Implications of the Acute and Chronic Inflammatory Response and the Foreign Body Reaction to the Immune Response of Implanted Biomaterials

  • Chapter
  • First Online:
The Immune Response to Implanted Materials and Devices

Abstract

In vivo implantation of medical devices, prostheses, biomaterials, and tissue-engineered scaffolds initiates the innate immune response consisting of acute inflammation, chronic inflammation, and the foreign body reaction (FBR) within the first 2 weeks following implantation. This chapter focuses on these humoral and cellular events occurring at the implant site immediately following implantation. Following injury/implantation, blood-material interactions occur and the provisional matrix is formed. Acute inflammation consisting predominantly of polymorphonuclear leukocytes follows but resolves quickly, usually within the first week if not sooner, depending on the extent of injury at the implant site. Chronic inflammation consisting of monocytes, macrophages, and lymphocytes follows acute inflammation. This process also resolves quickly with biocompatible materials leaving monocytes and macrophages to interact at the interface of the implanted device or material. The FBR at the interface with biomaterials is composed of macrophages, which may fuse together to form foreign body giant cells (FBGCs). Outside the FBR at the biomaterial interface, fibrosis and fibrous encapsulation occur in the final stages of the healing response to the implanted biomaterial. Numerous challenges including lack of understanding of these responses in vivo currently limit projection to clinical application of the respective medical device, prosthesis, or biomaterial. The end-stage of the innate immune response consisting of the FBR at the interface with fibrous encapsulation has received extensive attention over the past decade. Numerous efforts have been made to downregulate the activity of macrophages and FBGCs at the interface and to decrease/eliminate the fibrous capsule formation. Ultimately, the success or failure of medical devices, implants, biomaterials, and tissue-engineered constructs is modulated by the interaction between their characteristics, patient conditions, and surgical technique.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Williams DF (2008) On the mechanisms of biocompatibility. Biomaterials 29(20):2941–2953

    Article  Google Scholar 

  2. Anderson JM (2001) Biological responses to materials. Annu Rev Mater Res 31:81–110

    Article  Google Scholar 

  3. Kumar V, Abbas AK, Fausto N et al (2005) Robbins and Cotran pathologic basis of disease, vol 15, 7th edn. Elsevier Saunders, Philadelphia, p 1525

    Google Scholar 

  4. Zdolsek J, Eaton JW, Tang L (2007) Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans. J Transl Med 5:31

    Article  Google Scholar 

  5. Wiggins MJ, Wilkoff B, Anderson JM et al (2001) Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads. J Biomed Mater Res 58(3):302–307

    Article  Google Scholar 

  6. Christenson EM, Soofi W, Holm JL et al (2007) Biodegradable fumarate-based polyHIPEs as tissue engineering scaffolds. Biomacromolecules 8(12):3806–3814

    Article  Google Scholar 

  7. Christenson EM, Dadsetan M, Wiggins M et al (2004) Poly(carbonate urethane) and poly(ether urethane) biodegradation: in vivo studies. J Biomed Mater Res A 69(3):407–416

    Article  Google Scholar 

  8. Christenson EM, Anderson JM, Hiltner A (2004) Oxidative mechanisms of poly(carbonate urethane) and poly(ether urethane) biodegradation: in vivo and in vitro correlations. J Biomed Mater Res A 70(2):245–255

    Article  Google Scholar 

  9. Henson PM (1971) The immunologic release of constituents from neutrophil leukocytes. II. Mechanisms of release during phagocytosis, and adherence to nonphagocytosable surfaces. J Immunol 107(6):1547–1557

    Google Scholar 

  10. Marchant RE, Anderson JM, Dillingham EO (1986) In vivo biocompatibility studies. VII. Inflammatory response to polyethylene and to a cytotoxic polyvinylchloride. J Biomed Mater Res 20(1):37–50

    Article  Google Scholar 

  11. Yamaguchi K, Konishi H, Hara S et al (2001) Biocompatibility studies of titanium-based alloy pedicle screw and rod system: histological aspects. Spine J 1(4):260–268

    Article  Google Scholar 

  12. MacEwan MR, Brodbeck WG, Matsuda T et al (2005) Monocyte/lymphocyte interactions and the foreign body response: in vitro effects of biomaterial surface chemistry. J Biomed Mater Res A 74(3):285–293

    Article  Google Scholar 

  13. Brodbeck WG, Macewan M, Colton E et al (2005) Lymphocytes and the foreign body response: lymphocyte enhancement of macrophage adhesion and fusion. J Biomed Mater Res A 74(2):222–229

    Article  Google Scholar 

  14. Mooney JE, Rolfe BE, Osborne GW et al (2010) Cellular plasticity of inflammatory myeloid cells in the peritoneal foreign body response. Am J Pathol 176(1):369–380

    Article  Google Scholar 

  15. Gordon S, Pluddemann A (2013) Tissue macrophage heterogeneity: issues and prospects. Semin Immunopathol 35(5):533–540

    Article  Google Scholar 

  16. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35

    Article  Google Scholar 

  17. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969

    Article  Google Scholar 

  18. Mantovani A, Sozzani S, Locati M et al (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549–555

    Article  Google Scholar 

  19. Mantovani A, Sica A, Sozzani S et al (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686

    Article  Google Scholar 

  20. Silver IA, Murrills RJ, Etherington DJ (1988) Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res 175(2):266–276

    Article  Google Scholar 

  21. Klebanoff SJ (2005) Myeloperoxidase: friend and foe. J Leukoc Biol 77(5):598–625

    Article  Google Scholar 

  22. Jankowski A, Scott CC, Grinstein S (2002) Determinants of the phagosomal pH in neutrophils. J Biol Chem 277(8):6059–6066

    Article  Google Scholar 

  23. Haas A (2007) The phagosome: compartment with a license to kill. Traffic 8(4):311–330

    Article  Google Scholar 

  24. Nguyen LL, D’Amore PA (2001) Cellular interactions in vascular growth and differentiation. Int Rev Cytol 204:1–48

    Article  Google Scholar 

  25. Browder T, Folkman J, Pirie-Shepherd S (2000) The hemostatic system as a regulator of angiogenesis. J Biol Chem 275(3):1521–1524

    Article  Google Scholar 

  26. Hinz B, Phan SH, Thannickal VJ et al (2012) Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol 180(4):1340–1355

    Article  Google Scholar 

  27. Micallef L, Vedrenne N, Billet F et al (2012) The myofibroblast, multiple origins for major roles in normal and pathological tissue repair. Fibrogenesis Tissue Repair 5(Suppl 1):S5

    Google Scholar 

  28. Pierce GF (2001) Inflammation in nonhealing diabetic wounds: the space-time continuum does matter. Am J Pathol 159(2):399–403

    Article  Google Scholar 

  29. Mustoe TA, Pierce GF, Thomason A et al (1987) Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 237(4820):1333–1336

    Article  Google Scholar 

  30. Clark RAF (1996) The molecular and cellular biology of wound repair, vol 23, 2nd edn. Plenum Press, New York, p 611, 611 leaf of plates

    Google Scholar 

  31. Broughton G 2nd, Janis JE, Attinger CE (2006) The basic science of wound healing. Plast Reconstr Surg 117(7 Suppl):12S–34S

    Article  Google Scholar 

  32. Anderson JM, Rodriguez A, Chang DT (2008) Foreign body reaction to biomaterials. Semin Immunol 20(2):86–100

    Article  Google Scholar 

  33. Anderson JM, Cramer S (2015) Perspectives on the inflammatory, healing, and foreign body responses to biomaterials and medical devices. In: Badylak S (ed) Host response to biomaterials. The impact of host response on biomaterial selection. Elsevier, New York, pp 13–36

    Chapter  Google Scholar 

  34. Bota PC, Collie AM, Puolakkainen P et al (2010) Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro. J Biomed Mater Res A 95(2):649–657

    Article  Google Scholar 

  35. Revell PA (2008) The combined role of wear particles, macrophages and lymphocytes in the loosening of total joint prostheses. J R Soc Interface 5(28):1263–1278

    Article  Google Scholar 

  36. Charnley J (1970) The reaction of bone to self-curing acrylic cement. A long-term histological study in man. J Bone Joint Surg Br 52(2):340–353

    Google Scholar 

  37. Purdue PE (2008) Alternative macrophage activation in periprosthetic osteolysis. Autoimmunity 41(3):212–217

    Article  Google Scholar 

  38. Brodbeck WG, Anderson JM (2009) Giant cell formation and function. Curr Opin Hematol 16(1):53–57

    Article  Google Scholar 

  39. McNally AK, DeFife KM, Anderson JM (1996) Interleukin-4-induced macrophage fusion is prevented by inhibitors of mannose receptor activity. Am J Pathol 149(3):975–985

    Google Scholar 

  40. McNally AK, Anderson JM (1994) Complement C3 participation in monocyte adhesion to different surfaces. Proc Natl Acad Sci U S A 91(21):10119–10123

    Article  Google Scholar 

  41. Nilsson B, Ekdahl KN, Mollnes TE et al (2007) The role of complement in biomaterial-induced inflammation. Mol Immunol 44(1–3):82–94

    Article  Google Scholar 

  42. McNally AK, Macewan SR, Anderson JM (2007) alpha subunit partners to beta1 and beta2 integrins during IL-4-induced foreign body giant cell formation. J Biomed Mater Res A 82(3):568–574

    Article  Google Scholar 

  43. McNally AK, Jones JA, Macewan SR et al (2008) Vitronectin is a critical protein adhesion substrate for IL-4-induced foreign body giant cell formation. J Biomed Mater Res A 86(2):535–543

    Article  Google Scholar 

  44. McNally AK, Anderson JM (2002) Beta1 and beta2 integrins mediate adhesion during macrophage fusion and multinucleated foreign body giant cell formation. Am J Pathol 160(2):621–630

    Article  Google Scholar 

  45. Jenney CR, Anderson JM (2000) Adsorbed serum proteins responsible for surface dependent human macrophage behavior. J Biomed Mater Res 49(4):435–447

    Article  Google Scholar 

  46. Hynes RO, Zhao Q (2000) The evolution of cell adhesion. J Cell Biol 150(2):F89–F96

    Article  Google Scholar 

  47. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687

    Article  Google Scholar 

  48. Kyriakides TR (2015) Molecular events at tissue-biomaterial interface. In: Badylak SF (ed) Host response to biomaterials. The impact of host response on biomaterial selection. Elsevier, New York, pp 81–116

    Chapter  Google Scholar 

  49. Jones JA, Chang DT, Meyerson H et al (2007) Proteomic analysis and quantification of cytokines and chemokines from biomaterial surface-adherent macrophages and foreign body giant cells. J Biomed Mater Res A 83(3):585–596

    Article  Google Scholar 

  50. Chang DT, Colton E, Anderson JM (2009) Paracrine and juxtacrine lymphocyte enhancement of adherent macrophage and foreign body giant cell activation. J Biomed Mater Res A 89(2):490–498

    Article  Google Scholar 

  51. Anderson JM, Jones JA (2007) Phenotypic dichotomies in the foreign body reaction. Biomaterials 28(34):5114–5120

    Article  Google Scholar 

  52. Sieweke MH, Allen JE (2013) Beyond stem cells: self-renewal of differentiated macrophages. Science 342(6161):1242974

    Article  Google Scholar 

  53. Robbins CS, Hilgendorf I, Weber GF et al (2013) Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med 19(9):1166–1172

    Article  Google Scholar 

  54. Badylak SF (2016) Tissue regeneration. A scaffold immune microenvironment. Science 352(6283):298

    Article  Google Scholar 

  55. Wynn TA, Ramalingam TR (2012) Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 18(7):1028–1040

    Article  Google Scholar 

  56. Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214(2):199–210

    Article  Google Scholar 

  57. Hinz B, Mastrangelo D, Iselin CE et al (2001) Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol 159(3):1009–1020

    Article  Google Scholar 

  58. Hinz B (2007) Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 127(3):526–537

    Article  Google Scholar 

  59. Bucala R (2012) Review series—inflammation & fibrosis. Fibrocytes and fibrosis. QJM 105(6):505–508

    Article  Google Scholar 

  60. Farra R, Sheppard NF Jr, McCabe L et al (2012) First-in-human testing of a wirelessly controlled drug delivery microchip. Sci Transl Med 4(122):122ra121

    Article  Google Scholar 

  61. Hashimoto D, Chow A, Noizat C et al (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38(4):792–804

    Article  Google Scholar 

  62. Morais JM, Papadimitrakopoulos F, Burgess DJ (2010) Biomaterials/tissue interactions: possible solutions to overcome foreign body response. AAPS J 12(2):188–196

    Article  Google Scholar 

  63. Kourtzelis I, Rafail S, DeAngelis RA et al (2013) Inhibition of biomaterial-induced complement activation attenuates the inflammatory host response to implantation. FASEB J 27(7):2768–2776

    Article  Google Scholar 

  64. Ekdahl KN, Lambris JD, Elwing H et al (2011) Innate immunity activation on biomaterial surfaces: a mechanistic model and coping strategies. Adv Drug Deliv Rev 63(12):1042–1050

    Article  Google Scholar 

  65. Shive MS, Brodbeck WG, Anderson JM (2002) Activation of caspase 3 during shear stress-induced neutrophil apoptosis on biomaterials. J Biomed Mater Res 62(2):163–168

    Article  Google Scholar 

  66. Brodbeck WG, Shive MS, Colton E et al (2001) Influence of biomaterial surface chemistry on the apoptosis of adherent cells. J Biomed Mater Res 55(4):661–668

    Article  Google Scholar 

  67. Brodbeck WG, Patel J, Voskerician G et al (2002) Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo. Proc Natl Acad Sci U S A 99(16):10287–10292

    Article  Google Scholar 

  68. Brodbeck WG, Colton E, Anderson JM (2003) Effects of adsorbed heat labile serum proteins and fibrinogen on adhesion and apoptosis of monocytes/macrophages on biomaterials. J Mater Sci Mater Med 14(8):671–675

    Article  Google Scholar 

  69. Klingberg F, Hinz ES, White B (2013) The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol 229(2):298–309

    Article  Google Scholar 

  70. Hinz B, Gabbiani G (2010) Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives. F1000 Biol Rep 2:78

    Article  Google Scholar 

  71. Stachelek SJ, Finley MJ, Alferiev IS et al (2011) The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation. Biomaterials 32(19):4317–4326

    Article  Google Scholar 

  72. Finley MJ, Clark KA, Alferiev IS et al (2013) Intracellular signaling mechanisms associated with CD47 modified surfaces. Biomaterials 34(34):8640–8649

    Article  Google Scholar 

  73. Fukano Y, Usui ML, Underwood RA et al (2010) Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl methacrylate) implants in mice. J Biomed Mater Res A 94(4):1172–1186

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology, Macromolecular Science And Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

    James M. Anderson & Sirui Jiang

Authors
  1. James M. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sirui Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James M. Anderson .

Editor information

Editors and Affiliations

  1. Department of Life and Environmental Sciences, Marche Polytechnic University, Ancona, Italy

    Bruna Corradetti

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Anderson, J.M., Jiang, S. (2017). Implications of the Acute and Chronic Inflammatory Response and the Foreign Body Reaction to the Immune Response of Implanted Biomaterials. In: Corradetti, B. (eds) The Immune Response to Implanted Materials and Devices. Springer, Cham. https://doi.org/10.1007/978-3-319-45433-7_2

Download citation

Publish with us

Policies and ethics

Search

Navigation