Skip to main content

Advertisement

SpringerLink
Log in

Performance of evacuated calcium phosphate microcarriers loaded with mesenchymal stem cells within a rat calvarium defect

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

Abstract

Tissue engineering of stem cells in concert with 3-dimensional (3D) scaffolds is a promising approach for regeneration of bone tissues. Bioactive ceramic microspheres are considered effective 3D stem cell carriers for bone tissue engineering. Here we used evacuated calcium phosphate (CaP) microspheres as the carrier of mesenchymal stem cells (MSCs) derived from rat bone marrow. The performance of the CaP–MSCs construct in bone formation within a rat calvarium defect was evaluated. MSCs were first cultured in combination with the evacuated microcarriers for 7 days in an osteogenic medium, which was then implanted in the 6 mm-diameter calvarium defect for 12 weeks. For comparison purposes, a control defect and cell-free CaP microspheres were also evaluated. The osteogenic differentiation of MSCs cultivated in the evacuated CaP microcarriers was confirmed by alkaline phosphatase staining and real time polymerase chain reaction. The in vivo results confirmed the highest bone formation was attained in the CaP microcarriers combined with MSCs, based on microcomputed tomography and histological assays. The results suggest that evacuated CaP microspheres have the potential to be useful as stem cell carriers for bone tissue engineering.

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
Fig. 7

Similar content being viewed by others

References

  1. Damien CJ, Parsons JR. Bone graft and bone graft substitutes: a review of current technology and applications. J Appl Biomater. 1991;2:187–208.

    Article  CAS  Google Scholar 

  2. Shin SH, Purevdorj O, Castano O, Planell JA, Kim HW. A short review: recent advances in electrospinning for bone tissue regeneration. J Tissue Eng. 2012;. doi:10.1177/2041731412443530.

    Google Scholar 

  3. Perez RA, Won JE, Knowles JC, Kim HW. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv Drug Deliv Rev. 2012 doi:10.1016/j.addr.2012.03.009.

  4. Gu HJ, Lee HH, Kim HW. Microspheres of collagen-apatite nanocomposites with osteogenic potential for tissue engineering. Tissue Eng. 2007;13:965–73.

    Article  Google Scholar 

  5. Wu C, Pan J, Bao Z, Yu Y. Fabrication and characterization of chitosan microcarrier for hepatocyte culture. J Mater Sci Mater Med. 2007;18:2211–4.

    Article  CAS  Google Scholar 

  6. Hong SJ, Yu HS, Kim HW. Tissue engineering polymeric microcarriers with macroporous morphology and bone-bioactive surface. Macromol Biosci. 2009;9:639–45.

    Article  CAS  Google Scholar 

  7. Kim TK, Yoon JJ, Lee DS, Park TG. Gas foamed open porous biodegradable polymeric microspheres. Biomaterials. 2006;27:152–9.

    Article  Google Scholar 

  8. Overstreet M, Sohrabi A, Polotsky A, Hungerford DS, Frondoza CG. Collagen microcarrier spinner culture promotes osteoblast proliferation and synthesis of matrix proteins. In Vitro Cell Dev Biol Anim. 2003;39:228–34.

    Article  CAS  Google Scholar 

  9. Perez RA, Kim HW, Ginebra MP. Polymeric additives to enhance the functional properties of calcium phosphate cements. J Tissue Eng. 2012;. doi:10.1177/2041731412439555.

    Google Scholar 

  10. Rokstad AM, Holtan S, Strand B, Steinkjer B, Ryan L, Kulseng B, Skjak-Braek G, Qiu QQ, Ducheyne P, Ayyaswamy PS. New bioactive, degradable composite microspheres as tissue engineering substrates. J Biomed Mater Res. 2000;52:66–76.

    Article  Google Scholar 

  11. Maeda H, Kasuga T. Preparation of poly(lactic acid) composite hollow spheres containing calcium carbonates. Acta Biomater. 2006;2:403–8.

    Article  Google Scholar 

  12. Park JS, Hong SJ, Kim HY, Yu HS, Lee YI, Kim CH, Kwak SJ, Jang JH, Hyun JK, Kim HW. Evacuated calcium phosphate spherical microcarriers for bone regeneration. Tissue Eng Part A. 2010;16:1681–91.

    Article  CAS  Google Scholar 

  13. Nery EB, LeGeros RZ, Lynch KL, Lee K. Tissue response to biphasic calcium phosphate ceramic with different ratios of HA/beta TCP in periodontal osseous defects. J Periodontol. 1992;63:729–35.

    Article  CAS  Google Scholar 

  14. Schwartz C, Liss P, Jacquemaire B, Lecestre P, Frayssinet P. Biphasic synthetic bone substitute use in orthopaedic and trauma surgery: clinical, radiological and histological results. J Mater Sci Mater Med. 1999;10:821–5.

    Article  CAS  Google Scholar 

  15. Kim HW, Knowles JC, Kim HE. Effect of biphasic calcium phosphates on drug release and biological and mechanical properties of poly(epsilon-caprolactone) composite membranes. J Biomed Mater Res A. 2004;70:467–79.

    Article  Google Scholar 

  16. Lee HH, Hong SJ, Kim CH, Kim EC, Jang JH, Shin HI, Kim HW. Preparation of hydroxyapatite spheres with an internal cavity as a scaffold for hard tissue regeneration. J Mater Sci Mater Med. 2008;19:30293034.

    Google Scholar 

  17. Oh SA, Kim SH, Won JE, Kim JJ, Shin US, Kim HW. Effects on growth and osteogenic differentiation of mesenchymal stem cells by the zinc-added sol-gel bioactive glass granules. J Tissue Eng. 2010;. doi:10.4061/2010/475260.

    Google Scholar 

  18. Nam S, Won JE, Kim CH, Kim HW. Odontogenic differentiation of human dental pulp stem cells stimulated by the calcium phosphate porous granules. J Tissue Eng. 2011;. doi:10.4061/2011/812547.

    Google Scholar 

  19. Jegal SH, Park JH, Kim JH, Kim TH, Shin US, Kim TI, Kim HW. Functional composite nanofibers of poly(lactide-co-caprolactone) containing gelatin-apatite bone mimetic precipitate for bone regeneration. Acta Biomater. 2011;7:1609–17.

    Article  CAS  Google Scholar 

  20. Yoon E, Dhar S, Chun DE, Gharibjanian NA, Evans GR. In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co-glycolic acid constructs for bone regeneration in a rat critical-sized calvarial defect model. Tissue Eng. 2007;13:619–27.

    Article  CAS  Google Scholar 

  21. Anselme K, Noel B, Flautre B, Blary MC, Delecourt C, Descamps M, Hardouin P. Association of porous hydroxyapatite and bone marrow cells for bone regeneration. Bone. 1999;25:51S–4S.

    Article  CAS  Google Scholar 

  22. Kao CL, Tai LK, Chiou SH, Chen YJ, Lee KH, Chou SJ, Chang YL, Chang CM, Chen SJ, Ku HH, Li HY. Resveratrol promotes osteogenic differentiation and protects against dexamethasone damage in murine induced pluripotent stem cells. Stem Cells Dev. 2010;19:247–58.

    Article  CAS  Google Scholar 

  23. Castano-Izquierdo H, Alvarez-Barreto J, van den Dolder J, Jansen JA, Mikos AG, Sikavitsas VI. Pre-culture period of mesenchymal stem cells in osteogenic media influences their in vivo bone forming potential. J Biomed Mater Res A. 2007;82:129–38.

    Google Scholar 

  24. Kruyt MC, de Bruijn JD, Wilson CE, Oner FC, van Blitterswijk CA, Verbout AJ, Dhert WJ. Viable osteogenic cells are obligatory for tissue-engineered ectopic bone formation in goats. Tissue Eng. 2003;9:327–36.

    Article  CAS  Google Scholar 

  25. Yang X, Walboomers XF, van den Beucken JJ, Bian Z, Fan M, Jansen JA. Hard tissue formation of STRO-1-selected rat dental pulp stem cells in vivo. Tissue Eng Part A. 2009;15:367–75.

    Article  CAS  Google Scholar 

  26. Sikavitsas VI, van den Dolder J, Bancroft GN, Jansen JA, Mikos AG. Influence of the in vitro culture period on the in vivo performance of cell/titanium bone tissue engineered constructs using a rat cranial critical size defect model. J Biomed Mater Res A. 2003;67:944–51.

    Article  Google Scholar 

  27. Vehof JW, Spauwen PH, Jansen JA. Bone formation in calcium-phosphate-coated titanium mesh. Biomaterials. 2000;21:2003–9.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Priority Research Centers Program (No. 2009-0093829) and WCU program (R31-10069) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology. Authors thank Dr. Kim T. H. for his kind help in preparation of tissue samples.

Author information

Authors and Affiliations

  1. Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330-714, Korea

    Guang-Zhen Jin, Joong-Hyun Kim, Jeong-Hui Park, Seong-Jun Choi & Hae-Won Kim

  2. Department of Nanobiomedical Science & WCU Research Center, Dankook University Graduate School, Cheonan, 330-714, Korea

    Guang-Zhen Jin, Jeong-Hui Park, Hae-Won Kim & Ivan Wall

  3. Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan, 330-714, Korea

    Hae-Won Kim

  4. Department of Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK

    Ivan Wall

Authors
  1. Guang-Zhen Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joong-Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeong-Hui Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seong-Jun Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hae-Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ivan Wall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hae-Won Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, GZ., Kim, JH., Park, JH. et al. Performance of evacuated calcium phosphate microcarriers loaded with mesenchymal stem cells within a rat calvarium defect. J Mater Sci: Mater Med 23, 1739–1748 (2012). https://doi.org/10.1007/s10856-012-4646-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4646-y

Keywords

Search

Navigation