Biomimetic nanocoating promotes osteoblast cell adhesion on biomedical implants


Implantation of dental and orthopaedic devices is affected by delayed or weak implant-bone integration and inadequate new bone formation. Innovative approaches have been sought to enhance implant-bone interaction to achieve rapid osseointegration. The aim of this study was to develop biomimetic polypeptide nanocoatings and to evaluate cell adhesion, proliferation, morphology, and biocompatibility of polypeptide nanocoatings on implant surfaces. A recently developed nanotechnology, i.e., electrostatic self-assembly, was applied to build polypeptide nanocoatings on implant models, i.e., stainless steel discs. Our in vitro tests using human osteoblast cells revealed that substantially more (one order magnitude higher) osteoblast cells were attached to polypeptide-coated, stainless steel discs than to uncoated discs within the first few hours of contact. The developed biomimetic nanocoatings may have great potential for dental and orthopaedic applications.

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  1. 1

    T. Albrektsson, C. Johansson: Osteoinduction, osteoconduction and osseointegration. Eur. Spine J. 10, S96 2001

    Google Scholar 

  2. 2

    M.J.A. Van Luyn, P.B. Van Wachem, R. Leta, E.H. Blaauw, P. Nieuwenhuis: Modulation of the tissue reaction to biomaterials. J. Mater. Sci.-Mater. Med. 5, 671 1994

    Google Scholar 

  3. 3

    H.I. Kalfas: Principles of bone healing. Neurosurg. Focus 10(4), E1 2001

    CAS  Google Scholar 

  4. 4

    R.J. Kowalski, A. Lisa, L.A. Ferrara, E.C. Benzel: Biomechanics of bone fusion. Neurosurg. Focus 10(4), E2 2001

    CAS  Google Scholar 

  5. 5

    Handbook of Polyelectrolytes and Their Applications, edited by S.K. Tripathy, J. Kumar, and H.S. Nalwa (American Scientific Publishers, Stevenson Ranch, CA, 2002), Vol. 1

  6. 6

    G. Decher: Fuzzy nanoassemblies: Toward layered polymeric multicomposites. Science 277, 5330 1232 1997

    CAS  Google Scholar 

  7. 7

    B. Li, D.T. Haynie: Multilayer biomimetics: Reversible covalent stabilization of a nanostructured biofilm. Biomacromolecules 5(5), 1667 2004

    CAS  Google Scholar 

  8. 8

    B. Li, D. Haynie, N. Palath, D. Janisch: Nano-scale biomimetics: Fabrication and optimization of stability of peptide-based thin films. J. Nanosci. Nanotechnol. 12(5), 2042 2005

    Google Scholar 

  9. 9

    B. Li, J. Rozas, D. Haynie: Structural stability of polypeptide nanofilms under extreme conditions. Biotechnol. Progr. 22(1), 111 2006

    Google Scholar 

  10. 10

    B. Ding, J. Kim, E. Kimura, S. Shiratori: Layer-by-layer structured films of TiO2 nanoparticles and poly(acrylic acid) on electrospun nanofibers. Nanotechnol. 15, 913 2004

    CAS  Google Scholar 

  11. 11

    A.J. Chung, M.F. Rubner: Methods of loading and releasing low molecular weight cationic molecules in weak polyelectrolyte multilayer films. Langmuir 18, 1176 2002

    CAS  Google Scholar 

  12. 12

    K.C. Wood, J.Q. Boedicker, D.M. Lynn, P.T. Hammond: Tunable drug release from hydrolytically degradable layer-by-layer thin films. Langmuir 21, 1603 2005

    CAS  Google Scholar 

  13. 13

    G.B. Sukhorukov, M. Brumen, E. Donath, H. Möhwald: Hollow polyelectrolyte shells: Exclusion of polymers and Donnan equilibrium. J. Phys. Chem. B 103, 6434 1999

    CAS  Google Scholar 

  14. 14

    M. Fang, P.S. Grant, M.J. McShane, G.B. Sukhorukov, V.O. Golub, Y.M. Lvov: Magnetic bio/nanoreactor with multilayer shells of glucose oxidase and inorganic nanoparticles. Langmuir 18(16), 6338 2002

    CAS  Google Scholar 

  15. 15

    T. Ogawa, B. Ding, Y. Sone, S. Shiratori: Super-hydrophobic surface of layer-by-layer structured films coated electrospun nanofibers. Nanotechnol. 18, 165607 2007

    Google Scholar 

  16. 16

    J.Y. Martin, Z. Schwartz, T.W. Hummert: Effect of titanium surface roughness on proliferation, differentiation, and protein synthesis of human osteoblast like-cells. J. Biomed. Mater. Res. 29, 389 1995

    CAS  Google Scholar 

  17. 17

    F.B. Bagambisa, H.F. Kappert, W. Schilli: Cellular and molecular events at the implant interface. J. Cran. Max. Fac. Surg. 22, 12 1994

    CAS  Google Scholar 

  18. 18

    C.S. Chen, M. Mrksich, S. Huang, G.M. Whitesides, G.E. Ingber: Geometric control of cell life and death. Science 276, 1425 1997

    CAS  Google Scholar 

  19. 19

    J.E. Davies, B. Causton, Y. Bovell, K. Davy, C.S. Sturt: The migration of osteoblasts over substrata of discrete surface charge. Biomaterials 7, 231 1986

    CAS  Google Scholar 

  20. 20

    J.J.J.P. van den Beucken, X.F. Walboomers, S.C.G. Leeuwenburgh, M.R.J. Vos, N.A.J.M. Sommerdijk, R.J.M. Nolte, J.A. Jansen: Multilayered DNA coatings: In vitro bioactivity studies and effects on osteoblast-like cell behavior. Acta Biomater. 3(4), 587 2007

    Google Scholar 

  21. 21

    Z.Y. Tang, Y. Wang, P. Podsiadlo, N.A. Kotov: Biomedical applications of layer-by-layer assembly: From biomimetics to tissue engineering. Adv. Mater. 18(24), 3203 2006

    CAS  Google Scholar 

  22. 22

    H.G. Zhu, J. Ji, J.C. Shen: Osteoblast growth promotion by protein electrostatic self-assembly on biodegradable poly(lactide). J. Biomater. Sci., Polym. Ed. 16(6), 761 2005

    CAS  Google Scholar 

  23. 23

    Y.B. Zhu, C.Y. Gao, T. He, X.Y. Liu, J.C. Shen: Layer-by-layer assembly to modify poly(L-lactic acid) surface toward improving its cytocompatibility to human endothelial cells. Biomacromolecules 4(2), 446 2003

    CAS  Google Scholar 

  24. 24

    S. Tajima, J.S.F. Chu, S. Li, K. Komvopoulos: Differential regulation of endothelial cell adhesion, spreading, and cytoskeleton on low-density polyethylene by nanotopography and surface chemistry modification induced by argon plasma treatment. J. Biomed. Mater. Res. 84A(3), 828 2008

    Google Scholar 

  25. 25

    R. Jimbo, T. Sawase, K. Baba, T. Kurogi, Y. Shibata, M. Atsuta: Enhanced initial cell responses to chemically modified anodized titanium. Clin. Implant Dent. Relat. Res. 10(1), 55 2008

    Google Scholar 

  26. 26

    K. Kirchhof, T. Groth: Surface modification of biomaterials to control adhesion of cells. Clin. Hemorheol. Microcirc. 39(1-4), 247 2008

    CAS  Google Scholar 

  27. 27

    C. Brunot, B. Grosgogeat, C. Picart, C. Lagneau, N. Jaffrezic-Renault, L. Ponsonnet: Response of fibroblast activity and polyelectrolyte multilayer films coating titanium. Dent. Mater. 24(8), 1025 2008

    CAS  Google Scholar 

  28. 28

    P.K. Sinha, F. Morris, S.A. Shah, R.S. Tuan: Surface composition of orthopaedic implant metals regulates cell attachment, spreading, and cytoskeletal organization of primary human osteoblasts in vitro. Clin. Orthop. Relat. Res. 305, 258 1994

    Google Scholar 

  29. 29

    Z. Schwartz, B.D. Boyan: Underlying mechanisms at the bone-biomaterial interface. J. Cell. Biochem. 56(3), 340 1994

    CAS  Google Scholar 

  30. 30

    Y.T. Sul, C. Johansson, E. Byon, T. Albrektsson: The bone response of oxidized bioactive and non-bioactive titanium implants. Biomaterials 26, 6720 2005

    CAS  Google Scholar 

  31. 31

    G. Giavaresi, F. Branda, F. Causa, G. Luciani, M. Fini, N. Nicoli Aldini, L. Rimondini, L. Ambrosio, R. Giardino: Poly(2-hydroxyethyl methacrylate) biomimetic coating to improve osseointegration of a PMMA/HA/glass composite implant: In vivo mechanical and histomorphometric assessments. Int. J. Artif. Organs 27, 674 2004

    CAS  Google Scholar 

  32. 32

    M.J. Biggs, R.G. Richards, N. Gadegaard, C.D. Wilkinson, M.J. Dalby: Regulation of implant surface cell adhesion: Characterization and quantification of S-phase primary osteoblast adhesions on biomimetic nanoscale substrates. J. Orthop. Res. 25, 273 2007

    CAS  Google Scholar 

  33. 33

    X. Liu, P.K. Chu, C. Ding: Surface modification of titanium, titanium alloys, and related materials for biomedical applications. Mater. Sci. Eng., R 47(3–4), 49 2004

    Google Scholar 

  34. 34

    K. Anselme, P. Linez, M. Bigerelle, D. Le Maguer, A. Le Maguer, P. Hardouin, H.F. Hildebrand, A. Iost, J.M. Leroy: The relative influence of the topography and chemistry of TiAl6V4 surfaces on osteoblastic cell behaviour. Biomaterials 21(15), 1567 2000

    CAS  Google Scholar 

  35. 35

    J. Lincks, B.D. Boyan, C.R. Blanchard, C.H. Lohmann, Y. Liu, D.L. Cochran, D.D. Dean, Z. Schwartz: Response of MG63 osteoblast-like cells to titanium and titanium alloy is dependent on surface roughness and composition. Biomaterials 19(23), 2219 1998

    CAS  Google Scholar 

  36. 36

    L. Saldana, N. Vilaboa, G. Valles, J. Gonzalez-Cabrero, L. Munuera: Osteoblast response to thermally oxidized Ti6Al4V alloy. J. Biomed. Mater. Res. A 73(1), 97 2005

    CAS  Google Scholar 

  37. 37

    Z.W. Ma, Z.W. Mao, C.Y. Gao: Surface modification and property analysis of biomedical polymers used for tissue engineering. Colloids Surf., B 60(2), 137 2007

    CAS  Google Scholar 

  38. 38

    Z.H. Liu, Y.P. Jiao, Z.Y. Zhang, C.R. Zhou: Surface modification of poly(L-lactic acid) by entrapment of chitosan and its derivatives to promote osteoblasts-like compatibility. J. Biomed. Mater. Res. A 83(4), 1110 2007

    Google Scholar 

  39. 39

    P.M. Lopez-Perez, A.P. Marques, R.M.P. da Silva, I. Pashkuleva, R.L. Reis: Effect of chitosan membrane surface modification via plasma induced polymerization on the adhesion of osteoblast-like cells. J. Mater. Chem. 17(38), 4064 2007

    CAS  Google Scholar 

  40. 40

    L.C. Baxter, V. Frauchiger, M. Textor, I. Gwynn, R.G. Richards: Fibroblast and osteoblast adhesion and morphology on calcium phosphate surfaces. Eur. Cell. Mater. 4, 1 2002

    CAS  Google Scholar 

  41. 41

    R.O. Hynes: Integrins: Versatility, modulation, and signaling in cell adhesion. Cell 69(1), 11 1992

    CAS  Google Scholar 

  42. 42

    A. Huttenlocher, R.R. Sandborg, A.F. Horwitz: Adhesion in cell migration. Curr. Opin. Cell Biol. 7(5), 697 1995

    CAS  Google Scholar 

  43. 43

    G. Gronowicz, M.B. McCarthy: Response of human osteoblasts to implant materials: Integrin-mediated adhesion. J. Orthop. Res. 14(6), 878 1996

    CAS  Google Scholar 

  44. 44

    L.Y. Liu, G. Chen, T. Chao, B.D. Ratner, E.H. Sage, S.Y. Jiang: Reduced foreign body reaction to implanted biomaterials by surface treatment with oriented osteopontin. J. Biomater. Sci., Polym. Ed. 19(6), 821 2008

    Google Scholar 

  45. 45

    L. Salata, P. Burgos, L. Rasmusson, A. Novaes, V. Papalexiou, C. Dahlin, L. Sennerby: Osseointegration of oxidized and turned implants in circumferential bone defects with and without adjunctive therapies: An experimental study on BMP-2 and autogenous bone graft in the dog mandible. Int. J. Oral Maxillofac. Surg. 36(1), 62 2008

    Google Scholar 

  46. 46

    X.H. Rausch-fan, Z. Qu, M. Wieland, M. Wieland, M. Matejka, A. Schedle: Differentiation and cytokine synthesis of human alveolar osteoblasts compared to osteoblast-like cells (MG63) in response to titanium surfaces. Dent. Mater. 24(1), 102 2008

    CAS  Google Scholar 

  47. 47

    B. Li, B. Jiang, B.M. Boyce, B.A. Lindsey: Local IL-12 incorporated in nanocoatings promising for preventing open fracture associated infection. Orthopaedic Research Society (ORS) Annual Meeting San Francisco, CA, March 2008

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Financial support from National Aeronautics and Space Administration, West Virginia Experimental Program to Stimulate Competitive Research, West Virginia University (WVU) Program to Stimulate Competitive Research, and WVU Senate Grant are acknowledged.

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Correspondence to Bingyun Li.

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Likibi, F., Jiang, B. & Li, B. Biomimetic nanocoating promotes osteoblast cell adhesion on biomedical implants. Journal of Materials Research 23, 3222–3228 (2008).

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