Creation of macroporous calcium phosphate cements as bone substitutes by using genipin-crosslinked gelatin microspheres

  • Meng Li
  • Xingyan Liu
  • Xudong Liu
  • Baofeng Ge
  • Keming Chen


Macroporous calcium phosphate cements (CPCs) were developed using genipin-crosslinked gelatin microspheres (GMs) with two weight ratios (2.5 wt% and 5 wt%). The initial setting time of the composite was prolonged by GMs. After GMs/CPCs were soaked in phosphate-buffered saline (PBS) for several weeks, macropores appeared as a result of the degradation of GMs. The presence of GMs accelerated the setting reaction and improved the structure of the composite. The compressive strength increased up to 12 MPa (2.5 wt% GMs/CPCs) and 14 MPa (5 wt% GMs/CPCs) after one week of PBS soaking, then gradually decreased to 9 MPa (2.5 wt% GMs/CPCs) and 7 MPa (5 wt% GMs/CPCs) after three weeks of soaking, and further to 6 MPa (2.5 wt% GMs/CPCs) and 2 MPa (5 wt% GMs/CPCs) after five weeks of soaking. CPCs with 2.5 wt% GMs were the most favorable composite in the tested samples. Cell experiments showed that rat osteoblasts displayed normal morphologies when exposed to the 2.5 wt% GMs/CPCs, and proliferation of the cells was also enhanced. An in vivo study showed that new bone tissue was able to grow into the pores that resulted from GM degradation. This study suggests that the new composite could be a promising candidate for use as a bone substitute under non-compression-loaded circumstances.


Compressive Strength Gelatin Bone Substitute Calcium Phosphate Cement Genipin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was funded by Medical Science Research Foundation of Chinese People’s Liberation Army (Grant Number of 06MA090) and Natural Science Foundation of Gansu Province (Grant Number of 0710RJZA068). CPCs were kindly supplied by Shanghai Rebone Biomaterials (China).


  1. 1.
    L. Comuzzi, E. Ooms, J.A. Jansen, Clin. Oral Implants Res. 13, 304 (2002). doi: 10.1034/j.1600-0501.2002.130311.x PubMedCrossRefGoogle Scholar
  2. 2.
    E.M. Ooms, J.G. Wolke, J.P. van der Waerden, J.A. Jansen, J. Biomed. Mater. Res. 61, 9 (2002). doi: 10.1002/jbm.10029 PubMedCrossRefGoogle Scholar
  3. 3.
    M.R. Sarkar, N. Wachter, P. Patka, L. Kinzl, J. Biomed. Mater. Res. 58, 329 (2001). doi:10.1002/1097-4636(2001)58:3<329::AID-JBM1025>3.0.CO;2-9PubMedCrossRefGoogle Scholar
  4. 4.
    R.Z. LeGeros, J.R. Parsons, G. Daculsi, F. Driessens, D. Lee, S.T. Liu, S. Metsger, D. Peterson, M. Walker, Ann. NY Acad. Sci. 523, 268 (1988). doi: 10.1111/j.1749-6632.1988.tb38519.x PubMedCrossRefADSGoogle Scholar
  5. 5.
    L.C. Chow, Monogr. Oral Sci. 18, 148 (2001). doi: 10.1159/000061653 PubMedCrossRefGoogle Scholar
  6. 6.
    M.F. Baslé, D. Chappard, F. Grizon, R. Filmon, J. Delecrin, G. Daculsi, A. Rebel, Calcif. Tissue Int. 53, 348 (1993). doi: 10.1007/BF01351842 PubMedCrossRefGoogle Scholar
  7. 7.
    C.M. Clokie, H. Moghadam, M.T. Jaskson, G.K. Sandor, J. Craniofac. Surg. 13, 111 (2002). doi: 10.1097/00001665-200201000-00026 PubMedCrossRefGoogle Scholar
  8. 8.
    H. Schliephake, R. Grubber, M. Dard, R. Wenz, S. Scholz, J. Biomed. Mater. Res. A 69, 382 (2004). doi: 10.1002/jbm.a.20121 PubMedCrossRefGoogle Scholar
  9. 9.
    P.Q. Ruhé, E.L. Hedberg-Dirk, N.T. Padron, P.H. Spauwen, J.A. Jansen, A.G. Mikos, Tissue Eng. 12, 789 (2006). doi: 10.1089/ten.2006.12.789 PubMedCrossRefGoogle Scholar
  10. 10.
    R.P. del Real, E. Ooms, J.G. Wolke, M. Vallet-Regí, J.A. Jansen, J. Biomed. Mater. Res. A 65, 30 (2003). doi: 10.1002/jbm.a.10432 PubMedCrossRefGoogle Scholar
  11. 11.
    S. Takagi, L.C. Chow, J. Mater. Sci. Mater. Med. 12, 135 (2001). doi: 10.1023/A:1008917910468 PubMedCrossRefGoogle Scholar
  12. 12.
    Y. Zhang, H.H. Xu, S. Takagi, L.C. Chow, J. Mater. Sci. Mater. Med. 5, 437 (2006). doi: 10.1007/s10856-006-8471-z CrossRefGoogle Scholar
  13. 13.
    H.H. Xu, M.D. Weir, E.F. Burguera, A.M. Fraser, Biomaterials 24, 4279 (2006). doi: 10.1016/j.biomaterials.2006.03.001 CrossRefGoogle Scholar
  14. 14.
    H.H. Xu, L.E. Carey, C.G. Simon Jr, Simon. J. Mater. Sci. Mater. Med. 18, 1345 (2007). doi: 10.1007/s10856-007-0146-x PubMedCrossRefGoogle Scholar
  15. 15.
    S. Hesaraki, F. Moztarzadeh, D. Sharifi, J. Biomed. Mater. Res. A 83, 80 (2007). doi: 10.1002/jbm.a.31196 PubMedGoogle Scholar
  16. 16.
    S. Sarda, M. Nilsson, M. Balcells, E. Fernandez, J. Biomed. Mater. Res. A 65, 215 (2003). doi: 10.1002/jbm.a.10458 PubMedCrossRefGoogle Scholar
  17. 17.
    D.P. Link, J. van den Dolder, W.J. Jurgens, J.G. Wolke, J.A. Jansen, Biomaterials 27, 4941 (2006). doi: 10.1016/j.biomaterials.2006.05.022 PubMedCrossRefGoogle Scholar
  18. 18.
    W.J. Habraken, J.G. Wolke, A.G. Mikos, J.A. Jansen, J. Biomater. Sci. Polym. Ed. 17, 1057 (2006). doi: 10.1163/156856206778366004 PubMedCrossRefGoogle Scholar
  19. 19.
    E.W. Bodde, O.C. Boerman, F.G. Russel, A.G. Mikos, P.H. Spauwen, J.A. Jansen, J. Biomed. Mater. Res. A [Jan 15, Epub ahead of print] (2008)Google Scholar
  20. 20.
    Z. Fei, Y. Hu, D. Wu, H. Wu, R. Lu, J. Bai, H. Song, J. Mater. Sci. Mater. Med. 19, 1109 (2008). doi: 10.1007/s10856-007-3050-5 PubMedCrossRefGoogle Scholar
  21. 21.
    P.Q. Ruhé, O.C. Boerman, F.G. Russel, P.H. Spauwen, A.G. Mikos, J.A. Jansen, J. Control Release 106, 162 (2005). doi: 10.1016/j.jconrel.2005.04.018 PubMedCrossRefGoogle Scholar
  22. 22.
    Z. Pan, P. Jiang, Q. Fan, B. Ma, H. Cai, J. Biomed. Mater. Res. B Appl. Biomater. 82, 246 (2007). doi: 10.1002/jbm.b.30727 PubMedGoogle Scholar
  23. 23.
    A. Bigi, B. Bracci, S. Panzavolta, Biomaterials 25, 2893 (2004). doi: 10.1016/j.biomaterials.2003.09.059 PubMedCrossRefGoogle Scholar
  24. 24.
    Y. Fujishiro, K. Takahashi, T. Sato, J. Biomed. Mater. Res. 54, 525 (2001). doi:10.1002/1097-4636(20010315)54:4<525::AID-JBM80>3.0.CO;2-#PubMedCrossRefGoogle Scholar
  25. 25.
    M.Y. Shie, D.C. Chen, C.Y. Wang, T.Y. Chiang, S.J. Ding, Acta Biomater. 4, 646 (2008). doi: 10.1016/j.actbio.2007.10.011 PubMedCrossRefGoogle Scholar
  26. 26.
    A. Bigi, P. Torricelli, M. Fini, B. Bracci, S. Panzavolta, L. Sturba, R. Giardino, Int. J. Artif. Organs 27, 664 (2004)PubMedGoogle Scholar
  27. 27.
    A. Bigi, S. Panzavolta, L. Sturba, P. Torricelli, M. Fini, R. Giardino, J. Biomed. Mater. Res. A 78, 739 (2006). doi: 10.1002/jbm.a.30765 PubMedGoogle Scholar
  28. 28.
    H.C. Liang, W.H. Chang, K.J. Lin, H.W. Sung, J. Biomed. Mater. Res. A 65, 271 (2003). doi: 10.1002/jbm.a.10476 PubMedCrossRefGoogle Scholar
  29. 29.
    H.J. Wei, H.H. Yang, C.H. Chen, W.W. Lin, S.C. Chen, P.H. Lai, Y. Chang, H.W. Sung, J. Control Release 120, 27 (2007). doi: 10.1016/j.jconrel.2007.04.005 PubMedCrossRefGoogle Scholar
  30. 30.
    M.I. Ugwoke, R. Kinget, J. Microencapsul. 15, 273 (1998). doi: 10.3109/02652049809006857 PubMedCrossRefGoogle Scholar
  31. 31.
    W.J. Habraken, L.T. de Jonge, J.G. Wolke, L. Yubao, A.G. Mikos, J.A. Jansen, J. Biomed. Mater.Res. A [Jan 11, Epub ahead of print] (2008)Google Scholar
  32. 32.
    L.E. Carey, H.H. Xu Jr, C.G. Simon, S. Takagi, L.C. Chow, Biomaterials 26, 5002 (2005). doi: 10.1016/j.biomaterials.2005.01.015 PubMedCrossRefGoogle Scholar
  33. 33.
    W.C. Vrouwenvelder, G.G. Groot, K. de Groot, Biomaterials 13, 382 (1992). doi: 10.1016/0142-9612(92)90044-O PubMedCrossRefGoogle Scholar
  34. 34.
    M. Kon, Y. Miyamoto, K. Asaoka, K. Ishikawa, H.H. Lee, Dent. Mater. J. 17, 223 (1998)PubMedGoogle Scholar
  35. 35.
    E. Ferna′ndez, F.J. Gil, M.P. Ginebra, F.C. Driessens, J.A. Planell, S.M. Best, J. Mater. Sci. Mater. Med. 10, 223 (1999). doi: 10.1023/A:1008958112257 CrossRefGoogle Scholar
  36. 36.
    H. el-Briak, D. Durand, J. Nurit, S. Munier, B. Pauvert, P. Boudeville, J. Biomed. Mater. Res. 63, 447 (2002). doi: 10.1002/jbm.10257 PubMedCrossRefGoogle Scholar
  37. 37.
    A.I. Itälä, H.O. Ylänen, C. Ekholm, K.H. Karlsson, H.T. Aro, J. Biomed. Mater. Res. 58, 679 (2001). doi: 10.1002/jbm.1069 PubMedCrossRefGoogle Scholar
  38. 38.
    H.W. Sung, R.N. Huang, L.L. Huang, C.C. Tsai, C.T. Chiu, J. Biomed. Mater. Res. 42, 560 (1998). doi:10.1002/(SICI)1097-4636(19981215)42:4<560::AID-JBM12>3.0.CO;2-IPubMedCrossRefGoogle Scholar
  39. 39.
    C.H. Yao, B.S. Liu, S.H. Hsu, Y.S. Chen, C.C. Tsai, J. Biomed. Mater. Res. A 69, 709 (2004). doi: 10.1002/jbm.a.30045 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Meng Li
    • 1
  • Xingyan Liu
    • 2
  • Xudong Liu
    • 2
  • Baofeng Ge
    • 2
  • Keming Chen
    • 2
  1. 1.Orthopedic Institute of Chinese People’s Liberation ArmyXijing Hospital, Fourth Military Medical UniversityXi’anPeople’s Republic of China
  2. 2.Orthopedic Trauma Institute of Chinese People’s Liberation ArmyLanzhou General HospitalLanzhouPeople’s Republic of China

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