Skip to main content

Advertisement

Log in

A novel cyclic RGD-containing peptide polymer improves serum-free adhesion of adipose tissue-derived mesenchymal stem cells to bone implant surfaces

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Seeding of bone implants with mesenchymal stem cells (MSCs) may promote osseointegration and bone regeneration. However, implant material surfaces, such as titanium or bovine bone mineral, fail to support rapid and efficient attachment of MSCs, especially under serum-free conditions that may be desirable when human applications or tightly controlled experiments are envisioned. Here we demonstrate that a branched poly[Lys(Seri-DL-Alam)] polymer functionalized with cyclic arginyl-glycyl-aspartate, when immobilized by simple adsorption to tissue culture plastic, surgical titanium alloy (Ti6Al4V), or Bio-Oss® bovine bone substitute, significantly accelerates serum-free adhesion and enhances seeding efficiency of human adipose tissue-derived MSCs. Moreover, when exposed to serum-containing osteogenic medium, MSCs survived and differentiated on the peptide-coated scaffolds. In summary, the presented novel polypeptide conjugate can be conveniently used for coating various surfaces, and may find applications whenever quick and efficient seeding of MSCs is required to various scaffolds in the absence of serum.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Morita Y, Yamasaki K, Hattori K. A feasibility study for in vitro evaluation of fixation between prosthesis and bone with bone marrow-derived mesenchymal stem cells. Clin Biomech. (Bristol, Avon) 2010;25:829–34.

    Google Scholar 

  2. van den Dolder J, Farber E, Spauwen PH, Jansen JA. Bone tissue reconstruction using titanium fiber mesh combined with rat bone marrow stromal cells. Biomaterials. 2003;24:1745–50.

    Article  Google Scholar 

  3. Holtorf HL, Jansen JA, Mikos AG. Ectopic bone formation in rat marrow stromal cell/titanium fiber mesh scaffold constructs: effect of initial cell phenotype. Biomaterials. 2005;26:6208–16.

    Article  CAS  Google Scholar 

  4. Zhou W, Han C, Song Y, Yan X, Li D, Chai Z, et al. The performance of bone marrow mesenchymal stem cell-implant complexes prepared by cell sheet engineering techniques. Biomaterials. 2010;31:3212–21.

    Article  CAS  Google Scholar 

  5. Mylonas D, Vidal MD, De Kok IJ, Moriarity JD, Cooper LF. Investigation of a thermoplastic polymeric carrier for bone tissue engineering using allogeneic mesenchymal stem cells in granular scaffolds. J Prosthodont. 2007;16:421–30.

    Article  Google Scholar 

  6. Rickert D, Sauerbier S, Nagursky H, Menne D, Vissink A, Raghoebar GM. Maxillary sinus floor elevation with bovine bone mineral combined with either autogenous bone or autogenous stem cells: a prospective randomized clinical trial. Clin Oral Implants Res. 2011;22:251–8.

    Article  CAS  Google Scholar 

  7. Choi HJ, Kim JM, Kwon E, Che JH, Lee JI, Cho SR, et al. Establishment of efficacy and safety assessment of human adipose tissue-derived mesenchymal stem cells (hATMSCs) in a nude rat femoral segmental defect model. J Korean Med Sci. 2011;26:482–91.

    Article  Google Scholar 

  8. Levi B, Longaker MT. Concise review: adipose-derived stromal cells for skeletal regenerative medicine. Stem Cells. 2011;29:576–82.

    Article  CAS  Google Scholar 

  9. Scherberich A, Müller AM, Schäfer DJ, Banfi A, Martin I. Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. J Cell Physiol. 2010;225:348–53.

    Article  CAS  Google Scholar 

  10. Gastaldi G, Asti A, Scaffino MF, Visai L, Saino E, Cometa AM, et al. Human adipose-derived stem cells (hASCs) proliferate and differentiate in osteoblast-like cells on trabecular titanium scaffolds. J Biomed Mater Res A. 2010;94:790–9.

    Google Scholar 

  11. Marino G, Rosso F, Cafiero G, Tortora C, Moraci M, Barbarisi M, et al. Beta-tricalcium phosphate 3D scaffold promote alone osteogenic differentiation of human adipose stem cells: in vitro study. J Mater Sci Mater Med. 2010;21:353–63.

    Article  CAS  Google Scholar 

  12. Hersel U, Dahmen C, Kessler H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials. 2003;24:4385–415.

    Article  CAS  Google Scholar 

  13. Porté-Durrieu MC, Guillemot F, Pallu S, Labrugère C, Brouillaud B, Bareille R, et al. Cyclo-(DfKRG) peptide grafting onto Ti-6Al-4V: physical characterization and interest towards human osteoprogenitor cells adhesion. Biomaterials. 2004;25:4837–46.

    Article  Google Scholar 

  14. Sawyer AA, Weeks DM, Kelpke SS, McCracken MS, Bellis SL. The effect of the addition of a polyglutamate motif to RGD on peptide tethering to hydroxyapatite and the promotion of mesenchymal stem cell adhesion. Biomaterials. 2005;26:7046–56.

    Article  CAS  Google Scholar 

  15. Chua PH, Neoh KG, Kang ET, Wang W. Surface functionalization of titanium with hyaluronic acid/chitosan polyelectrolyte multilayers and RGD for promoting osteoblast functions and inhibiting bacterial adhesion. Biomaterials. 2008;29:1412–21.

    Article  CAS  Google Scholar 

  16. Detsch R, Dieser I, Deisinger U, Uhl F, Hamisch S, Ziegler G, et al. Biofunctionalization of dispense-plotted hydroxyapatite scaffolds with peptides: quantification and cellular response. J Biomed Mater Res A. 2010;92:493–503.

    Google Scholar 

  17. Markó K, Ligeti M, Mezo G, Mihala N, Kutnyánszky E, Kiss E, et al. A novel synthetic peptide polymer with cyclic RGD motifs supports serum-free attachment of anchorage-dependent cells. Bioconjug Chem. 2008;19:1757–66.

    Article  Google Scholar 

  18. Mező G, Kajtár J, Nagy I, Szekerke M, Hudecz F. Carrier design: synthesis and conformational studies of poly(l-lysine)based branched polypeptides with hydroxyl groups in the side chains. Biopolymers. 1997;42:719–30.

    Article  Google Scholar 

  19. Mező G, de Oliveira E, Krikorian D, Feijlbrief M, Jakab A, Tsikaris V, et al. Synthesis and comparison of antibody recognition of conjugates containing herpes simplex virus type 1 glycoprotein D epitope VII. Bioconjug Chem. 2003;14:1260–9.

    Article  Google Scholar 

  20. Gurrath M, Müller G, Kessler H, Aumailley M, Timpl R. Conformation/activity studies of rationally designed potent anti-adhesive RGD peptides. Eur J Biochem. 1992;210:911–21.

    Article  CAS  Google Scholar 

  21. Lavenus S, Pilet P, Guicheux J, Weiss P, Louarn G, Layrolle P. Behaviour of mesenchymal stem cells, fibroblasts and osteoblasts on smooth surfaces. Acta Biomater. 2011;7:1525–34.

    Article  CAS  Google Scholar 

  22. Wiedmann-Al-Ahmad M, Gutwald R, Gellrich NC, Hübner U, Schmelzeisen R. Search for ideal biomaterials to cultivate human osteoblast-like cells for reconstructive surgery. J Mater Sci Mater Med. 2005;16:57–66.

    Article  CAS  Google Scholar 

  23. Herten M, Rothamel D, Schwarz F, Friesen K, Koegler G, Becker J. Surface- and nonsurface-dependent in vitro effects of bone substitutes on cell viability. Clin Oral Investig. 2009;13:149–55.

    Article  CAS  Google Scholar 

  24. Jafarian M, Eslaminejad MB, Khojasteh A, Abbas FM, Dehghan MM, Hassanizadeh R. Marrow-derived mesenchymal stem cells-directed bone regeneration in the dog mandible: a comparison between biphasic calcium phosphate and natural bone mineral. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:e14–24.

    Google Scholar 

  25. Yang C, Cheng K, Weng W, Yang C. Immobilization of RGD peptide on HA coating through a chemical bonding approach. J Mater Sci Mater Med. 2009;20:2349–52.

    Article  CAS  Google Scholar 

  26. Oya K, Tanaka Y, Saito H, Kurashima K, Nogi K, Tsutsumi H, et al. Calcification by MC3T3-E1 cells on RGD peptide immobilized on titanium through electrodeposited PEG. Biomaterials. 2009;30:1281–6.

    Article  CAS  Google Scholar 

  27. Durrieu MC, Pallu S, Guillemot F, Bareille R, Amédée J, Baquey CH, et al. Grafting RGD containing peptides onto hydroxyapatite to promote osteoblastic cells adhesion. J Mater Sci Mater Med. 2004;15:779–86.

    Article  CAS  Google Scholar 

  28. Hennessy KM, Clem WC, Phipps MC, Sawyer AA, Shaikh FM, Bellis SL. The effect of RGD peptides on osseointegration of hydroxyapatite biomaterials. Biomaterials. 2008;29:3075–83.

    Article  CAS  Google Scholar 

  29. Galli D, Benedetti L, Bongio M, Maliardi V, Silvani G, Ceccarelli G, et al. In vitro osteoblastic differentiation of human mesenchymal stem cells and human dental pulp stem cells on poly-l-lysine-treated titanium-6-aluminium-4-vanadium. J Biomed Mater Res A. 2011;97:118–26.

    Google Scholar 

  30. Subbiahdoss G, Pidhatika B, Coullerez G, Charnley M, Kuijer R, van der Mei HC, et al. Bacterial biofilm formation versus mammalian cell growth on titanium-based mono- and bi-functional coating. Eur Cell Mater. 2010;19:205–13.

    CAS  Google Scholar 

  31. Germanier Y, Tosatti S, Broggini N, Textor M, Buser D. Enhanced bone apposition around biofunctionalized sandblasted and acid-etched titanium implant surfaces. A histomorphometric study in miniature pigs. Clin Oral Implants Res. 2006;17:251–7.

    Article  Google Scholar 

  32. Schliephake H, Scharnweber D, Dard M, Sewing A, Aref A, Roessler S. Functionalization of dental implant surfaces using adhesion molecules. J Biomed Mater Res B Appl Biomater. 2005;73:88–96.

    CAS  Google Scholar 

  33. Stadlinger B, Pilling E, Huhle M, Khavkin E, Bierbaum S, Scharnweber D, et al. Suitability of differently designed matrix-based implant surface coatings: an animal study on bone formation. J Biomed Mater Res B Appl Biomater. 2008;87:516–24.

    Google Scholar 

  34. Ferris DM, Moodie GD, Dimond PM, Gioranni CW, Ehrlich MG, Valentini RF. RGD-coated titanium implants stimulate increased bone formation in vivo. Biomaterials. 1999;20:2323–31.

    Article  CAS  Google Scholar 

  35. Schliephake H, Scharnweber D, Dard M, Rössler S, Sewing A, Meyer J, Hoogestraat D. Effect of RGD peptide coating of titanium implants on periimplant bone formation in the alveolar crest. An experimental pilot study in dogs. Clin Oral Implants Res. 2002;13:312–9.

    Article  Google Scholar 

  36. Elmengaard B, Bechtold JE, Søballe K. In vivo study of the effect of RGD treatment on bone ongrowth on press-fit titanium alloy implants. Biomaterials. 2005;26:3521–6.

    Article  CAS  Google Scholar 

  37. Rammelt S, Illert T, Bierbaum S, Scharnweber D, Zwipp H, Schneiders W. Coating of titanium implants with collagen: RGD peptide and chondroitin sulfate. Biomaterials. 2006;27:5561–71.

    Article  CAS  Google Scholar 

  38. Pallu S, Fricain JC, Bareille R, Bourget C, Dard M, Sewing A, et al. Cyclo-DfKRG peptide modulates in vitro and in vivo behavior of human osteoprogenitor cells on titanium alloys. Acta Biomater. 2009;5:3581–92.

    Article  CAS  Google Scholar 

  39. Schneider D, Weber FE, Hämmerle CH, Feloutzis A, Jung RE. Bone regeneration using a synthetic matrix containing enamel matrix derivate. Clin Oral Implants Res. 2011;22:214–22.

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank all colleagues at the Tissue Regeneration Department of the Twente University for the kind support, as well as Éva Juhász and Balázs Hegedűs for the help with time-lapse microscopy. This work was financially supported by the grants BIO_SURF from the National Office for Research and Technology (NKTH) and TÁMOP-4.2.1-IKUT from the National Development Agency (NFÜ).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katalin Német.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tátrai, P., Sági, B., Szigeti, A. et al. A novel cyclic RGD-containing peptide polymer improves serum-free adhesion of adipose tissue-derived mesenchymal stem cells to bone implant surfaces. J Mater Sci: Mater Med 24, 479–488 (2013). https://doi.org/10.1007/s10856-012-4809-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4809-x

Keywords

Navigation