The method of surface PEGylation influences leukocyte adhesion and activation

  • Z. Ademovic
  • B. Holst
  • R. A. Kahn
  • I. Jørring
  • T. Brevig
  • J. Wei
  • X. Hou
  • B. Winter-Jensen
  • P. KingshottEmail author


The influence of different surface modifications with poly(ethyleneglycol) (PEG) layers on the adsorption of fibrinogen and the adhesion and activation of macrophage-like human leukocytes was investigated. Poly(ethylene terephthalate) (PET) was modified using pulsed AC plasma polymerization with two types of starting monomers to generate: 1) a reactive acid surface using maleic anhydride (MAH) as monomer, and 2) a PEG-like surface using diethyleneglycol methyl vinyl ether (DEGVE) as monomer. The MAH surface was used as a reactive platform to graft linear chains of non-fouling mPEG via an intermediate layer of poly(ethyleneimine) (PEI) under lower critical solution temperature (LCST) conditions of the mPEG. The DEGVE monomer is used to create PEG-like layers by use of low power plasma conditions. The ability of the surfaces to resist protein adsorption was investigated quantitatively using 125I-radiolabeled human fibrinogen, and the conformation of the adsorbed protein was tested using an anti-fibrinogen monoclonal antibody in an enzyme-linked immunosorbent assay. The results showed that PEGylated surfaces adsorbed significantly less (up to 90% less) fibrinogen, and that unfolding of adsorbed fibrinogen was more pronounced on the linear mPEG layers than on the PEG-like plasma polymer surfaces. Adhesion of in-vitro differentiated macrophage-like U937 cells was reduced on both the PEG-like plasma polymer surfaces and the linear mPEG layers compared to the unmodified PET surface, but cells adhering to the PEG-like plasma polymer surfaces secreted less tumor necrosis factor-α (TNF- α) than cells adhering to the linear mPEG layers. In conclusion, the method for preparing non-fouling surfaces for long-term implanted devices influence surface-induced cellular responses of the host.


Fibrinogen Lower Critical Solution Temperature Vinyl Ether Maleic Anhydride Ethylene Terephthalate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    N. F. HASSAN, N. KAMANI, M. M. MESZAROS and S. D. DOUGLAS, J. Immunol. 143 (1989) 2179.Google Scholar
  2. 2.
    J. M. ANDERSON, ASAIO Trains. 11 (1988) 101.Google Scholar
  3. 3.
    P. THOMSEN and C. GRETZER, Curr. Opin. Solid State Mater. Sci. 5 (2001) 163.Google Scholar
  4. 4.
    M. SHEN and T. A. HORBETT, J. Biomed. Mater. Res. 57 (2001) 336.CrossRefGoogle Scholar
  5. 5.
    G. BERTON and C. A. LOWELL, Cell Signal. 11 (1999) 621.CrossRefGoogle Scholar
  6. 6.
    N. P. ZIATS, K. M. MILLER and J. M. ANDERSON, Biomaterials 9 (1988) 5.CrossRefGoogle Scholar
  7. 7.
    K. M. MILLER and J. M. ANDERSON, J. Biomed. Mater. Res. 22 (1988) 713.CrossRefGoogle Scholar
  8. 8.
    D. Y. UNG, K. A. WOODHOUSE and M. V. SEFTON, J. Biomed. Mater. Res. 46 (1999) 324.CrossRefGoogle Scholar
  9. 9.
    C. JENNEY and J. ANDERSON, J. Biomed. Mater. Res. 49 (2000) 435.CrossRefGoogle Scholar
  10. 10.
    A. ROSENGREN, L. M. BJURSTEN, N. DANIELSEN, H. PERSSON and M. KOBER, J. Mater. Sci.: Mater. Med. 10 (1999) 75.CrossRefGoogle Scholar
  11. 11.
    W. G. BRODBECK, M. S. SHIVE, E. COLTON, Y. NAKAYAMA, T. MATSUDA and J. M. ANDERSON, J. Biomed. Mater. Res. 55 (2001) 661.CrossRefGoogle Scholar
  12. 12.
    W. G. BRODBECK, G. VOSKERICIAN, N. P. ZIATS, Y. NAKAYAMA, T. MATSUDA and J. M. ANDERSON, J. Biomed. Mater. Res. 64 (2003) 320.Google Scholar
  13. 13.
    W. G. BRODBECK, Y. NAKAYAMA, T. MATSUDA, E. COLTON, N. P. ZIATS and J. M. ANDERSON, Cytokine 18(2002) 311.CrossRefGoogle Scholar
  14. 14.
    J. H. LEE, H. B. LEE and J. D. ANDRADE, Prog. Polym. Sci. 20 (1995) 1043.CrossRefGoogle Scholar
  15. 15.
    S. I. JEON, J. H. LEE, J. D. ANDRADE and P. G. DEGANNES, J. Colloid and Interface Sci. 142 (1991) 149.Google Scholar
  16. 16.
    I. SZLEIFER, Physica A 1 (1997) 370.Google Scholar
  17. 17.
    W. J. KAO and J. A. HUBBELL, Biotechnol. Bioengr. 59 (1998) 2.Google Scholar
  18. 18.
    C. R. JENNEY and J. M. ANDERSON, J. Biomed. Mater. Res. 44 (1999) 206.CrossRefGoogle Scholar
  19. 19.
    M. C. SHEN, Y. V. PAN, M. S. WAGNER, K. D: HAUCH, D. G. CASTNER, B. D. RATNER and T. A. HORBETT, J. Biomater. Sci., Polym. Ed. 12 (2001) 961.Google Scholar
  20. 20.
    L. TANG and J. W. EATON, J. Exp. Med. 178 (1996) 2147.Google Scholar
  21. 21.
    W. G. BRODBECK, E. COLTON and J. M. ANDERSON, J. Mater. Sci.: Mater. In Med. 14 (2003) 671.Google Scholar
  22. 22.
    L. TANG, T. P. UGAROVA, E. F. PLOW and J. W. EATON, J. Clin. Invest. 97 (1996) 1329.Google Scholar
  23. 23.
    L. TANG and J. W. EATON, J. Exp. Med. 178 (1993) 2147.CrossRefGoogle Scholar
  24. 24.
    D. C. ALTIERI, J. PLESCIA and E. F. PLOW, J. Biol. Chem. 268 (1993) 1847.Google Scholar
  25. 25.
    T. P. UGAROVA, D. A. SOLOVJOV, L. ZHANG, D. I. LOUKINOV, V. C. YEE, L. V. MEDVED and E. F. PLOW, J. Biol. Chem. 273 (1998) 22519.CrossRefGoogle Scholar
  26. 26.
    W. J. HU, J. W. EATON, T. P. UGAROVA, and L. TANG, Blood 98 (2001) 1231.CrossRefGoogle Scholar
  27. 27.
    D. C. ALTIERI, A. DUPERRAY, J. PLESCIA, G. B. THORNTON, and L. R. LANGUINO, J. Biol. Chem. 270 (1995) 696.Google Scholar
  28. 28.
    S. T. SMILEY, J. A. KING, and W. W. HANCOCK, J. Immunol. 167(2001) 2887.Google Scholar
  29. 29.
    T. BREVIG, B. HOLST, Z. ADEMOVIC, N. ROZLOSNIK, J. H. RØHRMANN, N. B. LARSEN, O. C. HANSEN and P. KINGSHOTT, Biomaterials 26 (2005) 3039.CrossRefGoogle Scholar
  30. 30.
    Z. ADEMOVIC, J. WEI, B. WINTHER-JENSEN, X. HOU and P. KINGSHOTT, Plasma Processes and Polymers 2 (2005), 53.CrossRefGoogle Scholar
  31. 31.
    P. KINGSHOTT, H. THIESSEN and H. J. GRIESSER, Biomaterials 23 (2002) 2043.Google Scholar
  32. 32.
    R. R. COBB and J. L. MOLONY, FEBS Lett. 394 (1996) 241.CrossRefGoogle Scholar
  33. 33.
    P. KINGSHOTT, K.BREMMELL, Z. ADEMOVIC and H. J. GRIESSER, manuscript in preparation.Google Scholar
  34. 34.
    M. BALCELLS, D. KLEE, M. FABRY and H. HOECKER, J. Colloid Interf. Sci. 220 (1999) 198.Google Scholar
  35. 35.
    L. TANG, T. P. UGAROVA, E. F. PLOW and J. W. EATON, J. Clin. Invest. 97 (1996) 1329.Google Scholar
  36. 36.
    P. THOMSEN and C. GRETZER, Curr. Opin. Sol. State Mat. Sci. 5 (2001) 163.Google Scholar
  37. 37.
    Z. ADEMOVIC, R. KHAN, T.BREVIG, X. HOU and B. WINTER-JENSEN, 19th European Conference on Biomaterials ESB2005, Sorrento, Italy, 9–15th Sept. (2005).Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Z. Ademovic
    • 1
  • B. Holst
    • 2
  • R. A. Kahn
    • 2
  • I. Jørring
    • 2
  • T. Brevig
    • 2
  • J. Wei
    • 1
  • X. Hou
    • 3
  • B. Winter-Jensen
    • 1
  • P. Kingshott
    • 1
    Email author
  1. 1.Danish Polymer CentreRisø National LaboratoryRoskildeDenmark
  2. 2.Bioneer A/SMammalian Cell BiologyHørsholmDenmark
  3. 3.Nuclear Research DepartmentRisø National LaboratoryRoskildeDenmark

Personalised recommendations