Development of Provisional Extracellular Matrix on Biomaterials Interface: Lessons from In Vitro Cell Culture

  • George AltankovEmail author
  • Thomas Groth
  • Elisabeth Engel
  • Jonas Gustavsson
  • Marta Pegueroles
  • Conrado Aparicio
  • Francesc J. Gil
  • Maria-Pau Ginebra
  • Josep A. Planell
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)


The initial cellular events that take place at the biomaterials interface mimic to a certain extent the natural interaction of cells with the extracellular matrix (ECM). The cells adhering to the adsorbed soluble matrix proteins, such as fibronectin (FN) and fibrinogen (FNG) tend to re-arrange them in fibril-like pattern. Using model surfaces we have demonstrated that this cellular activity is abundantly dependent on the surface properties of materials, such as wettability, surface chemistry, charge and topography. This raises the possibility that tissue compatibility of materials is connected with the allowance of cells to remodel substratum associated proteins presumably to form provisional ECM. We have further shown that antibodies which bind β1 and αv integrins (subunits of the FN and FNG receptors respectively) may induce their linear rearrangement on the dorsal surface of living cells – a phenomenon presumably related to the same early molecular events of fibrillar matrix assembly. Because the quantitative measurements revealed that this receptor dynamics is strongly altered on the low compatible (hydrophobic) substrata we hypothesized that in order to be biocompatible, materials need to adsorb matrix proteins loosely, i.e. in such a way that the cells can easily remove and organize them in matrix-like fibrils via coordinated functioning of integrins. More recent studies on the fate of FN on some real biomaterial surfaces, including different rough titanium (Ti) and hydroxyapatite (HA) cements and the surface of biosensors confirmed this point of view. They also show that quantitative measurements of adsorbed matrix proteins and their dynamic rearrangement at cell-material interface might provide insight to the biocompatibility of given material and even predict its tissue integration.


Biomaterials interface Fibronectin matrix Reorganizattion Provisional ECM Cellular interaction 


  1. Altankov G, Grinnell F (1995) Fibronectin receptor internalization and AP-2 complex reorganization in potassium depleted fibroblasts. Exp Cell Res 216:299–309CrossRefGoogle Scholar
  2. Altankov G, Groth Th (1994) Reorganization of substratum-bound fibronectin on hydrophilic and hydrophobic materials is related to biocompatibility. J Mater Sci: Mater Med 5:732–737CrossRefGoogle Scholar
  3. Altankov G, Groth Th (1996) Fibronectin matrix formation and the biocompatibility of materials. J Mater Sci: Mater Med 7:425–429CrossRefGoogle Scholar
  4. Altankov G, Groth Th, Krasteva N, Albrecht W, Paul D (1997) Morphological evidence for different fibronectin receptor organization and function during fibroblast adhesion on hydrophilic and hydrophobic glass substrata. J Biomater Sci Polym Ed 8:721–740CrossRefGoogle Scholar
  5. Altankov G, Hecht J, Dimoudis N (2001) Serum-free cultured keratinocytes fail to organize fibronectin matrix and possess different distribution of beta-1 integrins. Exp Dermatol 10:80–89CrossRefGoogle Scholar
  6. Altankov G, Albrecht W, Richau K, Groth Th, Lendlein A (2005) On the tissue compatibility of poly(ether imide) membranes: an in vitro study on their interaction with human dermal fibroblast and keratinocytes. J Biomater Sci Polym Ed 16(1):23–42CrossRefGoogle Scholar
  7. Anselme K, Bigerelle M, Noel B, Dufresne E, Judas D, Iost A, Hardouin P (2000) Qualitative and quantitative study of human osteoblast adhesion on materials with various surface roughnesses. J Biomed Mater Res 49:155–166CrossRefGoogle Scholar
  8. Aparicio C, Gil FJ, Planell JA, Engel E (2002) Human osteoblast proliferation and differentiation on grit-blasted and bioactive titanium for dental applications. J Mater Sci: Mater Med 13:1105–1111CrossRefGoogle Scholar
  9. Baumann WH, Lehmann M, Schwinde A, Ehret R, Brischwein M, Wolf B (1999) Microelectric sensor system for microphysiological application on living cells. Sens Actuat B 55:77–89CrossRefGoogle Scholar
  10. Boyan BD, Lohmann CH, Dean DD, Sylvia VL, Cochran DL, Schwartz Z (2001) Mechanisms involved in osteoblast response to implant surface morphology. Annu Rev Mater Res 31:357–371CrossRefGoogle Scholar
  11. Chesmel KD, Clark CC, Brighton CT, Black J (1995) Cellular-responses to chemical and morphologic aspects of biomaterial surfaces. Biosynthetic and migratory response of bone cell-populations. J Biomed Mater Res 29:1101–1110CrossRefGoogle Scholar
  12. Clark RA, Lanigan JM, DellaPelle P, Manseau E, Dvorak HF, Colvin RB (1982) Fibronectin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization. J Invest Dermatol 79:264–269CrossRefGoogle Scholar
  13. Coelho NM, Sánches MS, Plannell J, Altankov G (2009) Assembly of adsorbed type IV collagen on hydrophilic and hydrophobic substrata determine its biological activity (under preparation)Google Scholar
  14. Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF (2001) Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation, differentiation and detachment strength. Biomaterials 22(1):87–89CrossRefGoogle Scholar
  15. Denen EHJ, Sonneveld P, Brakebusch C, Fassler R, Sonneberg A (2002) The fibronectin binding integrins a5b1 and avb3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesionism and fibronectin fibrillogenesis. J Cell Biol 159:1071–1086CrossRefGoogle Scholar
  16. Donaldson DJ, Mahan JT, Amrani D, Hawiger J (1989) Fibrinogen-mediated epidermal cell migration: structural correlates for fibrinogen function. J Cell Sci 94:101–108Google Scholar
  17. Eisenbarth E, Linez P, Biehl V, Velten D, Breme J, Hildebrand HF (2002) Cell orientation and cytoskeleton organisation on ground titanium surfaces. Biomol Eng 19:233–237CrossRefGoogle Scholar
  18. Engel E, Del Valle S, Aparicio C, Altankov G, Asin L, Planell JA, Ginebra MP (2008). Discerning the role of topography and ion exchange in cell response to bioactive tissue engineering scaffolds. Tissue Engineering Part A 14(8):1341–1351CrossRefGoogle Scholar
  19. Ginebra MP, Driessens FC, Planell JA (2004) Effect of the particle size on the micro and nanostructural features of a calcium phosphate cement: a kinetic analysis. Biomaterials 25(17):3453–3462CrossRefGoogle Scholar
  20. Griffin L, Naughton G (2002) Tissue engineering – current challenges and expanding opportunities. Science 259:1009–1014CrossRefGoogle Scholar
  21. Grinnell F (1986) Focal adhesion sites and the removal of substratum-bound fibronectin. J Cell Biol 103:2697–2706CrossRefGoogle Scholar
  22. Gronowiez G, DeRome ME, McCarthy MB (1991) Glucocorticoids inhibit fibronectin synthesis and messenger RNA levels in cultured reat parietal bones. Endocrinology 128:1007–1114Google Scholar
  23. Groth Th, Altankov G (1996) Studies on the cell-biomaterial interaction: role of tyrosine phosphorylation during fibroblasts spreading on surfaces varying in wettability. Biomaterials 17:1227–1234CrossRefGoogle Scholar
  24. Gustavsson J, Altankov G, Errachid A, Samitier J, Planell J, Engel E (2007) Surface modifications of silicon nitride for biosensors application. J Mater Sci: Mater Med 19(4):1839–1850CrossRefGoogle Scholar
  25. Henche LL, Polak JM (2002) Third generation biomedical materials. Science 259:1014–1017CrossRefGoogle Scholar
  26. Hynes RO (1990) Fibronectins. Springer, New YorkCrossRefGoogle Scholar
  27. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–678CrossRefGoogle Scholar
  28. Jayaraman M, Meyer U, Buhner M, Joos U, Wiesmann HP (2004) Influence of titanium surfaces on attachment of osteoblast-like cells in vitro. Biomaterials 25:625–631CrossRefGoogle Scholar
  29. Kue R, Sohrabi A, Nagle D, Frondoza C, Hungerford D (1999) Enhanced proliferation and osteocalcin production by human osteoblast like MG-63 cells on silicon nitride ceramic discs. Biomaterials 20:1195–1201CrossRefGoogle Scholar
  30. Lange R, Luthen F, Beck U, Rychly J, Baumann A, Nebe B (2002) Cell-extracellular matrix interaction and physico-chemical characteristics of titanium surfaces depend on the roughness of the material. Biomol Eng 19:255–261CrossRefGoogle Scholar
  31. Lowenstaim HA, Weiner S (1989) On biomineralisation. Oxford University Press, OxfordGoogle Scholar
  32. Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23(1):47–55CrossRefGoogle Scholar
  33. Maneva-Radicheva L, Ebert U, Dimoudis N, Altankov G (2008) Fibroblast remodeling of collagen type IV is altered in contact with cáncer cells. Histol Histopathol 23:833–841Google Scholar
  34. Maursi AM, Damsky CH, Lull J, Zimmerman D, Doty S, Aota S-I, Globus RK (1996) Fibronectin regulates calvarial osteoblasts differentiation. J Cell Sci 109:1369–1380Google Scholar
  35. Neumann A, Reske T, Held M, Jahnke K, Ragov C, Maier HR (2004) Comparative investigation of the biocompatibility of various silicon nitride ceramic qualities in vitro. J Mater Sci: Mater Med 15(10):1135–1140CrossRefGoogle Scholar
  36. Nordahi J, Mangarelli-Widholm S, Hultenby K, Reinholt FP (1995) Ultrastructural immunolocalization of fibronectin in epiphyseal and metaphyseal bone of young rats. Calcif Tissue Int 57:442–449CrossRefGoogle Scholar
  37. Pankov R, Cukierman E, Katz B-Z, Matsumoto K, Lin DC, Lin Sh, Hahn C, Yamada K (2000) Integrin dynamics and Matrix Assembly: tensin-dependent translocation of a5b1 Integrins promotes Early Fibronectin Fibrillogenesis. J Cell Biol 148:1075–1090CrossRefGoogle Scholar
  38. Pegueroles M, Bosio M, Gil FJ, Planell JA, Engel E, Aparicio C, Altankov G (2009) Development of early fibronectin matrix by osteoblasts on different rough titanium interface. Acta Biomater (in press). Available in Internet. doi:10.1016/j.actbio.2009.07Google Scholar
  39. Pereira M, Rybarczyk BJ, Odrljin TM, Hocking DC, Sottile J, Simpson-Haidaris J (2002) The incorporation of fibrinogen into extracellular matrix is dependent on active assembly of a fibronectin. J Cell Sci 115:609–617Google Scholar
  40. Ponsonnet L, Reybier K, Jaffrezic N, Comte V, Lagneau C, Lissac M, Martelet C (2003) Relationship between surface properties (roughness, wettability) of titanium and titanium alloys and cell behaviour. Mater Sci Eng C-Biomim Supramol Syst 23:551–560CrossRefGoogle Scholar
  41. Richards RG (1996) The effect of surface roughness on fibroblast adhesion in vitro. Inj-Int J Care Inj 27:38–43Google Scholar
  42. Schöning MJ, Thust M, Müller-Veggian M, Kordoš P, Lüth H (1998) A novel silicon-based sensor array with capacitive EIS structures. Sens Actuat B 47:225–230CrossRefGoogle Scholar
  43. Schwartz Z, Martin JY, Dean DD, Simpson J, Cochran DL, Boyan BD (1996) Effect of titanium surface roughness on chondrocyte proliferation, matrix production, and differentiation depends on the state of cell maturation. J Biomed Mater Res 30:145–155CrossRefGoogle Scholar
  44. Sohrabi A, Holland C, Kue R, Nagle D, Hungerford DS, Frondoza CG (2000) Proinflammatory cytokine expression of IL-1 and TNF- by human osteoblast-like MG-63 cells upon exposure to silicon nitride in vitro. J Biomed Mater Res 50(1):43–49CrossRefGoogle Scholar
  45. Spie J (2002) Tissue engineering and reparative medicine. Ann NY Acad Sci 961:1–9CrossRefGoogle Scholar
  46. Thiery JP (2003) Cell adhesion in development: a complex signaling network. Curr Opin Genet Dev 13:365–371CrossRefGoogle Scholar
  47. Tzoneva R, Groth Th, Altankov G, Paul D (2002) Remodeling of fibrinogen by endothelial cells in dependence of fibronectin matrix assembly. Effect of substratum wettability. J Mater Sci Mater Med 13:1235–1244CrossRefGoogle Scholar
  48. Yamad KM, Pankov R, Cuycerman E (2003) Dymensions and dynamics of integrin functiom. J Med Biol Res 36:959–966Google Scholar
  49. Yuasa T, Miyamoto Y, Ishikawa K, Takechi M, Momota Y, Tatehara S, Nagayama M (2004) Effects of apatite cements on proliferation and differentiation of human osteoblasts in vitro. Biomaterials 25:1159–1166CrossRefGoogle Scholar
  50. Zamir E, Geiger B (2001) Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114:3583–3590Google Scholar
  51. Zlatanov A, Groth Th, Lendlein A, Altankov G (2005) Dinamics of β1- integrin in living fibroblast-effect of substratum wettability. Biophys J 89:3555–3562CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • George Altankov
    • 1
    • 2
    • 4
    Email author
  • Thomas Groth
    • 5
  • Elisabeth Engel
    • 3
  • Jonas Gustavsson
    • 3
  • Marta Pegueroles
    • 3
  • Conrado Aparicio
    • 3
  • Francesc J. Gil
    • 3
  • Maria-Pau Ginebra
    • 3
  • Josep A. Planell
    • 3
  1. 1.Institute of Biophysics Bulgarian Academy of SciencesSofiaBulgaria
  2. 2.ICREA (Institucio Catala para Recercia i Estudis Avancats)BarcelonaSpain
  3. 3.Institute for Bioengineering of CataluniaL’Hospitalet de Llobregat BarcelonaSpain
  4. 4.Department of PharmacyMartin-Luther University Halle-WittenbergHalle (Saale)Germany
  5. 5.Department of Material ScienceUniversitat Politècnica de CatalunyaBarcelonaSpain

Personalised recommendations