Skip to main content
SpringerLink
Log in

Stem cell engineered bone with calcium-phosphate coated porous titanium scaffold or silicon hydroxyapatite granules for revision total joint arthroplasty

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

Abstract

Aseptic loosening in total joint replacements (TJRs) is mainly caused by osteolysis which leads to a reduction of the bone stock necessary for implant fixation in revision TJRs. Our aim was to develop bone tissue-engineered constructs based on scaffolds of clinical relevance in revision TJRs to reconstitute the bone stock at revision operations by using a perfusion bioreactor system (PBRS). The hypothesis was that a PBRS will enhance mesenchymal stem cells (MSCs) proliferation and osteogenic differentiation and will provide an even distribution of MSCs throughout the scaffolds when compared to static cultures. A PBRS was designed and implemented. Scaffolds, silicon substituted hydroxyapatite granules and calcium-phosphate coated porous TiAl6V4 cylinders, were seeded with MSCs and cultured either in static conditions or in the PBRS at 0.75 mL/min. Statistically significant increased cell proliferation and alkaline phosphatase activity was found in samples cultured in the PBRS. Histology revealed a more even cell distribution in the perfused constructs. SEM showed that cells arranged in sheets. Long cytoplasmic processes attached the cells to the scaffolds. We conclude that a novel tissue engineering approach to address the issue of poor bone stock at revision operations is feasible by using a PBRS.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Harris WH. The problem is osteolysis. Clin Orthop Relat Res. 1995;311:46–53.

    Google Scholar 

  2. Harris WH. Wear and periprosthetic osteolysis. Clin Orthop Relat Res. 2001;393:66–70.

    Article  Google Scholar 

  3. Amstutz HC, Campbell P, Kossovsky N, Clarke IC. Mechanism and clinical significance of wear debris-induced osteolysis. Clin Orthop Relat Res. 1992;276:7–18.

    Google Scholar 

  4. Moore WR, Graves SE, Bain GI. Synthetic bone graft substitutes. ANZ J Surg. 2001;71:354–61.

    Article  Google Scholar 

  5. Vaccaro AR. The role of the osteoconductive scaffold in synthetic bone graft. Orthopaedics. 2002;25:S571–8.

    Google Scholar 

  6. Lanza RP, Langer R, Vacanti J. Principles of tissue engineering. 2nd ed. New York: Academic press; 2000.

    Google Scholar 

  7. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci. 2004;4:743–65.

    Article  Google Scholar 

  8. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26:5474–91.

    Article  Google Scholar 

  9. Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials. 1999;20:2287–303.

    Article  Google Scholar 

  10. LeGeros RZ. Calcium phosphate-based osteoinductive materials. Chem Rev. 2008;108:4742–53.

    Article  Google Scholar 

  11. Niinomi M. Mechanical biocompatibilities of titanium alloys for biomedical applications. J Mech Behav Biomed Mater. 2008;1(1):30–42.

    Article  Google Scholar 

  12. Bobyn JD, Stackpool GJ, Hacking SA, et al. Characteristics of bone ingrowth and interface mechanics of a new porous tantalum biomaterial. J Bone Joint Surg. 1999;81(5):907–14.

    Article  Google Scholar 

  13. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9(5):641–50.

    Article  Google Scholar 

  14. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  Google Scholar 

  15. Ohgushi H, Dohi Y, Tamai S, Tabata S. Osteogenic differentiation of marrow stromal stem cells in porous hydroxyapatite ceramics. J Biomed Mater Res. 1993;27:1401–7.

    Article  Google Scholar 

  16. Oreffo ROC, Driessens FCM, Planell JA, Triffitt JT. Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements. Biomaterials. 1998;9:1845–54.

    Article  Google Scholar 

  17. Nishio K, Neo M, Akiyama H, et al. The effect of alkali-and heat-treated titanium and apatite-formed titanium on osteoblastic differentiation of bone marrow cells. J Biomed Mater Res. 2000;52(4):652–61.

    Article  Google Scholar 

  18. García-Gareta E, Hua J, Knowles JC, Blunn GW. Comparison of mesenchymal stem cell proliferation and differentiation between biomimetic and electrochemical coatings on different topographic surfaces. J Mater Sci Mater Med. 2013;24(1):199–210.

    Article  Google Scholar 

  19. Sensebé L, Krampera M, Schrezenmeier H, et al. Mesenchymal stem cells for clinical application. Vox Sang. 2010;98:93–107.

    Article  Google Scholar 

  20. Kale S, Biermann S, Edwards C, et al. Three-dimensional cellular development is essential for ex vivo formation of human bone. Nat Biotechnol. 2000;18:954–8.

    Article  Google Scholar 

  21. Bancroft GN, Sikavitsas VI, Mikos AG. Design of a perfusion bioreactor system for bone tissue-engineering applications. Tissue Eng. 2003;9(3):549–54.

    Article  Google Scholar 

  22. Martin I, Wendt D, Heberer M. The role of bioreactors in tissue engineering. Trends Biotechnol. 2004;22(2):80–6.

    Article  Google Scholar 

  23. Sikavitsas V, Bancroft GN, Holtorf HL, et al. Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. PNAS. 2003;100(25):14683–8.

    Article  Google Scholar 

  24. Scaglione S, Braccini A, Wendt D, et al. Engineering of osteoinductive grafts by isolation and expansion of ovine bone marrow stromal cells directly on 3D ceramic scaffolds. Biotechnol Bioeng. 2006;93(1):181–7.

    Article  Google Scholar 

  25. Fröhlich M, Grayson WL, Marolt D, et al. Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng Part A. 2010;16(1):179–89.

    Article  Google Scholar 

  26. Janssen FW, van Dijkhuizen-Radersma R, Van Oorschot A, et al. Human tissue-engineered bone produced in clinically relevant amounts using a semi-automated perfusion bioreactor system: a preliminary study. J Tissue Eng Regen Med. 2010;4(1):12–24.

    Google Scholar 

  27. Redepenning J, Schlessinger T, Burnham S, et al. Characterization of electrolytically prepared brushite and hydroxyapatite coatings on orthopaedic alloys. J Biomed Mater Res. 1996;30:287–94.

    Article  Google Scholar 

  28. Cartmell SH, Porter BD, Garcia AJ, Guldberg RE. Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs in vitro. Tissue Eng. 2003;9(6):1197–203.

    Article  Google Scholar 

  29. Janssen FW, Oostra J, van Oorschot A, van Blitterswijk CA. A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. Biomaterials. 2006;27:315–23.

    Article  Google Scholar 

  30. Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem. 1997;64:295–312.

    Article  Google Scholar 

  31. Bruder SP, Jaiswal N, Haynesworth SE. Growth kinetics, self-renewal and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem. 1997;64:278–94.

    Article  Google Scholar 

  32. Lian JB, Stein GS. Concepts of osteoblast growth and differentiation: basis for modulation of bone cell development and tissue formation. Crit Rev Oral Biol Med. 1992;3(3):269–305.

    Google Scholar 

  33. Hara M, Murakami T, Kobayashi E. In vivo bioimaging using photogenic rats: fate of injected bone marrow-derived mesenchymal stromal cells. J Autoimmun. 2008;30:163–71.

    Article  Google Scholar 

  34. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109:235–42.

    Article  Google Scholar 

  35. Gie GA, Linder L, Ling RS, et al. Impacted cancellous allografts and cement for revision total hip arthroplasty. J Bone Joint Surg. 1993;75B(1):14–21.

    Google Scholar 

  36. Board TN, Rooney P, Keerney JN, Kay PR. Impaction allografting in revision total hip replacement. J Bone Joint Surg. 2006;88(7):852–7.

    Article  Google Scholar 

  37. Korda M, Blunn G, Goodhip A, Hua J. Use of mesenchymal stem cells to enhance bone formation around revision hip replacements. J Orthop Res. 2008;26:880–5.

    Article  Google Scholar 

  38. Levine BR, Sporer S, Poggie RA, et al. Experimental and clinical performance of porous tantalum in orthopaedic surgery. Biomaterials. 2006;27:4671–81.

    Article  Google Scholar 

  39. Sikavitsas V, Bancroft GN, Lemoine JL, et al. Flow perfusion enhances the calcified matrix deposition of marrow stromal cells in biodegradable nonwoven fiber mesh scaffolds. Ann Biomed Eng. 2005;33(1):63–70.

    Article  Google Scholar 

  40. Bjerre L, Bünger CE, Kassem M, Mygind T. Flow perfusion culture of human mesenchymal stem cells on silicate-substituted tricalcium phosphate scaffolds. Biomaterials. 2008;29:2616–27.

    Article  Google Scholar 

  41. Bancroft GN, Sikavitsas VI, van den Dolder J, et al. Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci USA. 2002;99(20):12600–5.

    Article  Google Scholar 

  42. Zhao F, Chella R, Ma T. Effects of shear stress on 3D human mesenchymal stem cell construct development in a perfusion bioreactor system: experiments and hydrodynamic modelling. Biotechnol Bioeng. 2007;96(3):584–95.

    Article  Google Scholar 

  43. Bereither-Hahn J, Münnich A, Woiteneck P. Dependence of energy metabolism on the density of cells in culture. Cell Struct Funct. 1998;23(2):85–93.

    Article  Google Scholar 

  44. Holtorf HI, Sheffield TL, Ambrose CG, et al. Flow perfusion culture of marrow stromal cells seeded on porous biphasic calcium phosphate ceramics. Ann Biomed Eng. 2005;33(9):1238–48.

    Article  Google Scholar 

  45. Mygind T, Stiehler M, Baatrup A, et al. Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. Biomaterials. 2007;28:1036–47.

    Article  Google Scholar 

  46. Dalby MJ, McCloy D, Robertson M, et al. Osteoprogenitor response to semi-ordered and random nanotopographies. Biomaterials. 2006;27:2980–7.

    Article  Google Scholar 

  47. Chatterjea A, Renard AJ, Jolink C, et al. Streamlining the generation of an osteogenic graft by 3D culture of unprocessed bone marrow on ceramic scaffolds. J Tissue Regen Med. 2012;6(2):103–12.

    Article  Google Scholar 

  48. Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am. 2005;87(7):1430–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, HA7 4LP, London, UK

    Elena García-Gareta, Jia Hua, Faizal Rayan & Gordon W. Blunn

Authors
  1. Elena García-Gareta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faizal Rayan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gordon W. Blunn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elena García-Gareta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

García-Gareta, E., Hua, J., Rayan, F. et al. Stem cell engineered bone with calcium-phosphate coated porous titanium scaffold or silicon hydroxyapatite granules for revision total joint arthroplasty. J Mater Sci: Mater Med 25, 1553–1562 (2014). https://doi.org/10.1007/s10856-014-5170-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-014-5170-z

Keywords

Search

Navigation