Skip to main content
SpringerLink
Log in

Modulation of Innate Immune Response for Tissue Engineering

  • Chapter
  • First Online:
Biomedical Engineering: Frontier Research and Converging Technologies

Part of the book series: Biosystems & Biorobotics ((BIOSYSROB,volume 9))

  • 2357 Accesses

Abstract

The number of biomaterial scaffolds for tissue engineering applications continues to rise and holds promise for regenerative medicine. However, the complexity of the immune response poses a challenging environment for implanted biomaterial scaffolds for tissue repair. Specifically, the innate immune responses characterized by tissue infiltrating neutrophils and macrophages have been shown to govern either pro-inflammatory or tissue reparative microenvironments at the local site of tissue injury depending on their activation and phenotypic status. Thus, a selective strategy for developing immune-modulatory biomaterial scaffolds to improve the modulation of innate immune reactions may offer attractive features for tissue regeneration. The focus of this chapter is to discuss recent progress in the development of biomaterial scaffolds for modulating immune responses and their potential application for tissue repair. Specifically, important design variables for fabricating immuno-modulatory biomaterial scaffolds are highlighted.

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 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bryers, J.D., Giachelli, C.M., Ratner, B.D.: Engineering biomaterials to integrate and heal: the biocompatibility paradigm shifts. Biotechnol. Bioeng. 109, 1898–1911 (2012)

    Article  Google Scholar 

  2. Miller, L.S., O’Connell, R.M., Gutierrez, M.A., Pietras, E.M., Shahangian, A., et al.: MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity 24, 79–91 (2006)

    Article  Google Scholar 

  3. Ekdahl, K.N., Lambris, J.D., Elwing, H., Ricklin, D., Nilsson, P.H., et al.: Innate immunity activation on biomaterial surfaces: a mechanistic model and coping strategies. Adv. Drug Deliv. Rev. 63, 1042–1050 (2011)

    Article  Google Scholar 

  4. Eming, S.A., Krieg, T., Davidson, J.M.: Inflammation in wound repair: molecular and cellular mechanisms. J. Invest. Dermatol. 127, 514–525 (2007)

    Article  Google Scholar 

  5. Singer, A.J., Clark, R.A.: Cutaneous wound healing. N. Engl. J. Med. 341, 738–746 (1999)

    Article  Google Scholar 

  6. Kim, M.H., Liu, W., Borjesson, D.L., Curry, F.R., Miller, L.S., et al.: Dynamics of neutrophil infiltration during cutaneous wound healing and infection using fluorescence imaging. J. Invest. Dermatol. 128, 1812–1820 (2008)

    Article  Google Scholar 

  7. Kim, M.H., Gorouhi, F., Ramirez, S., Granick, J.L., Byrne, B.A., et al.: Catecholamine stress alters neutrophil trafficking and impairs wound healing by beta2-adrenergic receptor-mediated upregulation of IL-6. J. Invest. Dermatol. 134, 809–817 (2014)

    Article  Google Scholar 

  8. Haumer, M., Amighi, J., Exner, M., Mlekusch, W., Sabeti, S., et al.: Association of neutrophils and future cardiovascular events in patients with peripheral artery disease. J. Vasc. Surg. 41, 610–617 (2005)

    Article  Google Scholar 

  9. Pierce, G.F.: Inflammation in nonhealing diabetic wounds: the space-time continuum does matter. Am. J. Pathol. 159, 399–403 (2001)

    Article  Google Scholar 

  10. Manz, M.G., Boettcher, S.: Emergency granulopoiesis. Nat. Rev. Immunol. 14, 302–314 (2014)

    Article  Google Scholar 

  11. Kolaczkowska, E., Kubes, P.: Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159–175 (2013)

    Article  Google Scholar 

  12. Kim, M.H., Granick, J.L., Kwok, C., Walker, N.J., Borjesson, D.L., et al.: Neutrophil survival and c-kit(+)-progenitor proliferation in Staphylococcus aureus-infected skin wounds promote resolution. Blood 117, 3343–3352 (2011)

    Article  Google Scholar 

  13. Sindrilaru, A., Scharffetter-Kochanek, K.: Disclosure of the Culprits: Macrophages-Versatile Regulators of Wound Healing. Adv. Wound Care (New Rochelle) 2, 357–368 (2013)

    Article  Google Scholar 

  14. Parsonage, G., Filer, A., Bik, M., Hardie, D., Lax, S., et al.: Prolonged, granulocyte-macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha. Arthritis Res. Ther. 10, R47 (2008)

    Article  Google Scholar 

  15. Mosser, D.M., Edwards, J.P.: Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958–969 (2008)

    Article  Google Scholar 

  16. Ricardo, S.D., van Goor, H., Eddy, A.A.: Macrophage diversity in renal injury and repair. J. Clin. Invest. 118, 3522–3530 (2008)

    Article  Google Scholar 

  17. Novak, M.L., Koh, T.J.: Macrophage phenotypes during tissue repair. J. Leukoc. Biol. 93, 875–881 (2013)

    Article  Google Scholar 

  18. Sica, A., Mantovani, A.: Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787–795 (2012)

    Article  Google Scholar 

  19. Murray, P.J., Wynn, T.A.: Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723–737 (2011)

    Article  Google Scholar 

  20. Davies, L.C., Jenkins, S.J., Allen, J.E., Taylor, P.R.: Tissue-resident macrophages. Nat. Immunol. 14, 986–995 (2013)

    Article  Google Scholar 

  21. Michlewska, S., Dransfield, I., Megson, I.L., Rossi, A.G.: Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for TNF-alpha. FASEB J. 23, 844–854 (2009)

    Article  Google Scholar 

  22. Ariel, A., Serhan, C.N.: New Lives Given by Cell Death: Macrophage Differentiation Following Their Encounter with Apoptotic Leukocytes during the Resolution of Inflammation. Front. Immunol. 3, 4 (2012)

    Google Scholar 

  23. Feng, X., Deng, T., Zhang, Y., Su, S., Wei, C., et al.: Lipopolysaccharide inhibits macrophage phagocytosis of apoptotic neutrophils by regulating the production of tumour necrosis factor alpha and growth arrest-specific gene 6. Immunology 132, 287–295 (2011)

    Article  Google Scholar 

  24. Khanna, S., Biswas, S., Shang, Y., Collard, E., Azad, A., et al.: Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One 5, e9539 (2010)

    Article  Google Scholar 

  25. Manfredi, A.A., Iannacone, M., D’Auria, F., Rovere-Querini, P.: The disposal of dying cells in living tissues. Apoptosis 7, 153–161 (2002)

    Article  Google Scholar 

  26. Ren, Y., Savill, J.: Apoptosis: the importance of being eaten. Cell Death Differ. 5, 563–568 (1998)

    Article  Google Scholar 

  27. Savill, J., Dransfield, I., Gregory, C., Haslett, C.: A blast from the past: clearance of apoptotic cells regulates immune responses. Nat. Rev. Immunol. 2, 965–975 (2002)

    Article  Google Scholar 

  28. Voll, R.E., Herrmann, M., Roth, E.A., Stach, C., Kalden, J.R., et al.: Immunosuppressive effects of apoptotic cells. Nature 390, 350–351 (1997)

    Article  Google Scholar 

  29. Furth, M.E., Atala, A., Van Dyke, M.E.: Smart biomaterials design for tissue engineering and regenerative medicine. Biomaterials 28, 5068–5073 (2007)

    Article  Google Scholar 

  30. Pashuck, E.T., Stevens, M.M.: Designing regenerative biomaterial therapies for the clinic. Sci. Transl. Med. 4, 160–164 (2012)

    Article  Google Scholar 

  31. Langer, R., Tirrell, D.A.: Designing materials for biology and medicine. Nature 428, 487–492 (2004)

    Article  Google Scholar 

  32. O’Brien, F.J.: Biomaterials & scaffolds for tissue engineering. Materials Today 14, 88–95 (2011)

    Article  Google Scholar 

  33. Nicodemus, G.D., Bryant, S.J.: Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng. Part B Rev. 14, 149–165 (2008)

    Article  Google Scholar 

  34. Oakes, P.W., Patel, D.C., Morin, N.A., Zitterbart, D.P., Fabry, B., et al.: Neutrophil morphology and migration are affected by substrate elasticity. Blood 114, 1387–1395 (2009)

    Article  Google Scholar 

  35. Yeung, T., Georges, P.C., Flanagan, L.A., Marg, B., Ortiz, M., et al.: Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil. Cytoskeleton 60, 24–34 (2005)

    Article  Google Scholar 

  36. Stroka, K.M., Aranda-Espinoza, H.: Endothelial cell substrate stiffness influences neutrophil transmigration via myosin light chain kinase-dependent cell contraction. Blood 118, 1632–1640 (2011)

    Article  Google Scholar 

  37. Stroka, K.M., Aranda-Espinoza, H.: Neutrophils display biphasic relationship between migration and substrate stiffness. Cell Motil. Cytoskeleton 66, 328–341 (2009)

    Article  Google Scholar 

  38. Fereol, S., Fodil, R., Labat, B., Galiacy, S., Laurent, V.M., et al.: Sensitivity of alveolar macrophages to substrate mechanical and adhesive properties. Cell Motil. Cytoskeleton 63, 321–340 (2006)

    Article  Google Scholar 

  39. Patel, N.R., Bole, M., Chen, C., Hardin, C.C., Kho, A.T., et al.: Cell elasticity determines macrophage function. PLoS One 7, e41024 (2012)

    Article  Google Scholar 

  40. Blakney, A.K., Swartzlander, M.D., Bryant, S.J.: 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, 1375–1386 (2012)

    Article  Google Scholar 

  41. Kim, D.H., Han, K., Gupta, K., Kwon, K.W., Suh, K.Y., et al.: Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. Biomaterials 30, 5433–5444 (2009)

    Article  Google Scholar 

  42. Bershadsky, A., Kozlov, M., Geiger, B.: Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. Curr. Opin. Cell Biol. 18, 472–481 (2006)

    Article  Google Scholar 

  43. Kim, D.H., Provenzano, P.P., Smith, C.L., Levchenko, A.: Matrix nanotopography as a regulator of cell function. J. Cell Biol. 197, 351–360 (2012)

    Article  Google Scholar 

  44. Shive, M.S., Salloum, M.L., Anderson, J.M.: Shear stress-induced apoptosis of adherent neutrophils: a mechanism for persistence of cardiovascular device infections. Proc. Natl. Acad. Sci. U.S.A. 97, 6710–6715 (2000)

    Article  Google Scholar 

  45. Chang, S., Popowich, Y., Greco, R.S., Haimovich, B.: Neutrophil survival on biomaterials is determined by surface topography. J. Vasc. Surg. 37, 1082–1090 (2003)

    Article  Google Scholar 

  46. Kwon, K.W., Park, H., Song, K.H., Choi, J.C., Ahn, H., et al.: Nanotopography-guided migration of T cells. J. Immunol. 189, 2266–2273 (2012)

    Article  Google Scholar 

  47. Saino, E., Focarete, M.L., Gualandi, C., Emanuele, E., Cornaglia, A.I., et al.: Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines. Biomacromolecules 12, 1900–1911 (2011)

    Article  Google Scholar 

  48. Chen, S., Jones, J.A., Xu, Y., Low, H.Y., Anderson, J.M., et al.: Characterization of topographical effects on macrophage behavior in a foreign body response model. Biomaterials 31, 3479–3491 (2010)

    Article  Google Scholar 

  49. Waterfield, J.D., Ali, T.A., Nahid, F., Kusano, K., Brunette, D.M.: The effect of surface topography on early NFkappaB signaling in macrophages. J. Biomed. Mater. Res. A 95, 837–847 (2010)

    Article  Google Scholar 

  50. Veleirinho, B., Coelho, D.S., Dias, P.F., Maraschin, M., Pinto, R., et al.: Foreign body reaction associated with PET and PET/chitosan electrospun nanofibrous abdominal meshes. PLoS One 9, e95293 (2014)

    Article  Google Scholar 

  51. Ferraz, N., Hong, J., Santin, M., Karlsson Ott, M.: Nanoporosity of alumina surfaces induces different patterns of activation in adhering monocytes/macrophages. Int. J. Biomater. 2010, 402715 (2010)

    Article  Google Scholar 

  52. Beckstead, B.L., Tung, J.C., Liang, K.J., Tavakkol, Z., Usui, M.L., et al.: Methods to promote Notch signaling at the biomaterial interface and evaluation in a rafted organ culture model. J. Biomed. Mater. Res. A 91, 436–446 (2009)

    Article  Google Scholar 

  53. Linnes, M.P., Ratner, B.D., Giachelli, C.M.: A fibrinogen-based precision microporous scaffold for tissue engineering. Biomaterials 28, 5298–5306 (2007)

    Article  Google Scholar 

  54. Madden, L.R., Mortisen, D.J., Sussman, E.M., Dupras, S.K., Fugate, J.A., et al.: Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc. Natl. Acad. Sci. U.S.A. 107, 15211–15216 (2010)

    Article  Google Scholar 

  55. Osathanon, T., Giachelli, C.M., Somerman, M.J.: Immobilization of alkaline phosphatase on microporous nanofibrous fibrin scaffolds for bone tissue engineering. Biomaterials 30, 4513–4521 (2009)

    Article  Google Scholar 

  56. Osathanon, T., Linnes, M.L., Rajachar, R.M., Ratner, B.D., Somerman, M.J., et al.: Microporous nanofibrous fibrin-based scaffolds for bone tissue engineering. Biomaterials 29, 4091–4099 (2008)

    Article  Google Scholar 

  57. Saul, J.M., Linnes, M.P., Ratner, B.D., Giachelli, C.M., Pun, S.H.: Delivery of non-viral gene carriers from sphere-templated fibrin scaffolds for sustained transgene expression. Biomaterials 28, 4705–4716 (2007)

    Article  Google Scholar 

  58. Fukano, Y., Knowles, N.G., Usui, M.L., Underwood, R.A., Hauch, K.D., et al.: Characterization of an in vitro model for evaluating the interface between skin and percutaneous biomaterials. Wound Repair Regen. 14, 484–491 (2006)

    Article  Google Scholar 

  59. Sussman, E.M., Halpin, M.C., Muster, J., Moon, R.T., Ratner, B.D.: Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann. Biomed. Eng. 42, 1508–1516 (2014)

    Article  Google Scholar 

  60. Henry, S.J., Crocker, J.C., Hammer, D.A.: Ligand density elicits a phenotypic switch in human neutrophils. Integr. Biol. (Camb) 6, 348–356 (2014)

    Article  Google Scholar 

  61. Ratner, B.D., Bryant, S.J.: Biomaterials: where we have been and where we are going. Annu. Rev. Biomed. Eng. 6, 41–75 (2004)

    Article  Google Scholar 

  62. Sun, D.H., Trindade, M.C., Nakashima, Y., Maloney, W.J., Goodman, S.B., et al.: Human serum opsonization of orthopedic biomaterial particles: protein-binding and monocyte/macrophage activation in vitro. J. Biomed. Mater. Res. A 65, 290–298 (2003)

    Article  Google Scholar 

  63. Ingham, E., Fisher, J.: The role of macrophages in osteolysis of total joint replacement. Biomaterials 26, 1271–1286 (2005)

    Article  Google Scholar 

  64. Merkel, K.D., Erdmann, J.M., McHugh, K.P., Abu-Amer, Y., Ross, F.P., et al.: Tumor necrosis factor-alpha mediates orthopedic implant osteolysis. Am. J. Pathol. 154, 203–210 (1999)

    Article  Google Scholar 

  65. Jay, S.M., Shepherd, B.R., Andrejecsk, J.W., Kyriakides, T.R., Pober, J.S., et al.: Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization. Biomaterials 31, 3054–3062 (2010)

    Article  Google Scholar 

  66. Spiller, K.L., Anfang, R.R., Spiller, K.J., Ng, J., Nakazawa, K.R., et al.: The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials 35, 4477–4488 (2014)

    Article  Google Scholar 

  67. Spiller, K.L., Nassiri, S., Witherel, C.E., Anfang, R.R., Ng, J., et al.: Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37, 194–207 (2015)

    Article  Google Scholar 

  68. Gower, R.M., Boehler, R.M., Azarin, S.M., Ricci, C.F., Leonard, J.N., et al.: Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression. Biomaterials 35, 2024–2031 (2014)

    Article  Google Scholar 

  69. Sridharan, R., Cameron, A.R., Kelly, D.J., Kearney, C., O’Brien, F.J.: Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Materials Today (2015). doi:10.1016/j.mattod.2015.01.019

    Google Scholar 

  70. Anderson, J.M., Rodriguez, A., Chang, D.T.: Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA

    Min-Ho Kim

Authors
  1. Min-Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Min-Ho Kim .

Editor information

Editors and Affiliations

  1. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, Georgia, USA

    Hanjoong Jo

  2. Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, Alabama, USA

    Ho-Wook Jun

  3. Department of Mechanical Engineering Soft Biomechanics & Biomaterials Lab, Korea Advanced Institute of Science and Technology, Daejeon (KAIST), Korea (Republic of)

    Jennifer Shin

  4. Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea (Republic of)

    SangHoon Lee

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kim, MH. (2016). Modulation of Innate Immune Response for Tissue Engineering. In: Jo, H., Jun, HW., Shin, J., Lee, S. (eds) Biomedical Engineering: Frontier Research and Converging Technologies. Biosystems & Biorobotics, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-21813-7_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-21813-7_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-21812-0

  • Online ISBN: 978-3-319-21813-7

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation