Skip to main content

Journal for Biophysical Chemistry

Concurrent elution of calcium phosphate and macromolecules from alginate/chitosan hydrogel coatings

Abstract

The concurrent release of calcium phosphate and biomacromolecules may improve wound healing responses at the interface with ceramic materials of orthopaedic and dental implants. Hydrogel coatings consisting of a mixture of alginate and chitosan were doped and applied onto solid carriers with the aim of investigating their use as local delivery vehicles. Coatings containing both the model macromolecule FITC-dextran 70 kDa (FD 70) and dispersed calcium phosphate carbonate (CPC) nanoparticles were coated onto a solid, nonporous model substrate to study the concurrent release of FD 70 and calcium and phosphate ions from within the hydrogel. Hydrogel coatings containing only FD 70 were cast onto porous calcium phosphate coatings, similar to hydroxyapatite, to study the release of FD 70 from, and calcium and phosphate ions through, the hydrogel coating. Transmission electron microscopy showed good dispersion of the CPC nanoparticles, and scanning electron microscopy and atomic force microscopy showed that increased CPC loading resulted in an increase in surface roughness but to extents well below those affecting cell responses. The release of FD 70 from CPC-loaded coatings was similar to release from the hydrogel alone, although higher CPC loadings resulted in small changes. The release of FD 70 was better described by double or triple phase zero order release kinetics; this complex time dependence indicates that in addition to outdiffusion, other, time-dependent factors apply, such as swelling of the gel, as expected from the known effects of calcium ions on alginate. Calcium and phosphate ions were also released, with similar release kinetics, through the hydrogel layer from the underlying CaP layer. In either case, release decreased to negligible levels after 3 days, suggesting that the systems of this study are suitable for short-term concurrent release of water-soluble biomacromolecules and calcium and phosphate ions.

References

  1. 1

    B. D. Ratner, J. Mol. Recognit. 9, 617 (1996).

    Article  CAS  Google Scholar 

  2. 2

    D. A. Puleo and A. Nanci, Biomaterials 20, 2311 (1999).

    Article  CAS  Google Scholar 

  3. 3

    Y. Nakayama, J. Kim, S. Nishi, H. Ueno, and T. Matsuda, J. Biomed. Mater. Res. 57, 559 (2001).

    Article  CAS  Google Scholar 

  4. 4

    L. Rowan, P.W. Stratford, A.S. Taylor, and T.A. Vick, WO Patent No. 2001001957 (11 Jan 2001).

  5. 5

    J. Stamler, J. Loscalzo, and J.D. Folts, U.S. Patent No. 6255277 (3 July 2001).

  6. 6

    A. B. Anderson, Med. Device Technol. 14, 16 (2003).

    Google Scholar 

  7. 7

    H. W. Kim, J. C. Knowles, and H. E. Kim, J. Mater. Sci. Mater. Med. 16, 189 (2005).

    Article  Google Scholar 

  8. 8

    B. Lagerqvist, S. K. James, U. Stenestrand, J. Lindback, T. Nilsson, and L. Wallentin, N. Engl. J. Med. 356, 1009 (2007).

    Article  CAS  Google Scholar 

  9. 9

    P. Peng, N. H. Voelcker, S. Kumar, and H. J. Griesser, BioInterphases 2, 95 (2007).

    Article  CAS  Google Scholar 

  10. 10

    K. Soballe, Acta Orthop. Scand. 64, 1 (1993).

    Google Scholar 

  11. 11

    F. Barrere, C. M. van der Valk, R. A. J. Dalmeijer, C. A. van Blitterswijk, K. de Groot, and P. Layrolle, J. Biomed. Mater. Res., Part B: Appl. Biomater. 64A, 378 (2003).

    Article  CAS  Google Scholar 

  12. 12

    P. Habibovic, C.M. van der Valk, K. De Groot, and P. Layrolle, Key Eng. Mater. 240-242, 387 (2003).

    Article  CAS  Google Scholar 

  13. 13

    S. Langstaff, M. Sayer, T. J. N. Smith, and S. M. Pugh, Biomaterials 22, 135 (2001).

    Article  CAS  Google Scholar 

  14. 14

    C. P. Klein, P. Patka, J. G. Wolke, J. M. de Blieck-Hogervorst, and K. de Groot, Biomaterials 15, 146 (1994).

    Article  CAS  Google Scholar 

  15. 15

    C. J. Damien and J. R. Parsons, J. Biomed. Mater. Res., Part B: Appl. Biomater. 2, 187 (1991).

    CAS  Google Scholar 

  16. 16

    T. Matsumoto, M. Okazaki, M. Inoue, S. Ode, C. Chang-Chien, H. Nakao, Y. Hamada, and J. Takahashi, J. Biomed. Mater. Res. 60, 651 (2002).

    Article  CAS  Google Scholar 

  17. 17

    K. C. Blakeslee, A. Robert, and S. R. Condrate, J. Am. Ceram. Soc. 54, 559 (1971).

    Article  CAS  Google Scholar 

  18. 18

    C. Rey, B. Collins, T. Goehl, I. R. Dickson, and M. J. Glimcher, Calcif. Tissue Int. 45, 157 (1989).

    Article  CAS  Google Scholar 

  19. 19

    J. E. Barralet, S. M. Best, and W. Bonfield, Biomed. Mater. Eng. 6, 101 (1996).

    CAS  Google Scholar 

  20. 20

    P. Peng, S. Kumar, N. H. Voelcker, E. Szili, R. S. C. Smart, and H. J. Griesser, J. Biomed. Mater. Res., Part A 76A, 347 (2006).

    Article  CAS  Google Scholar 

  21. 21

    M. D. Weir, H. H. K. Xu, and C. G. Simon, J. Biomed. Mater. Res., Part A 77A, 487 (2006).

    Article  CAS  Google Scholar 

  22. 22

    D. W. Green, S. Mann, and R. O. C. Oreffo, Soft Matter 2, 732 (2006).

    Article  CAS  Google Scholar 

  23. 23

    G. Fuentes, M. Gonzalez, G. Perez, J. A. Delgado, E. Peon, M. L. Rojas, J. Casquero, and P. Miranda, Lat. Am. Appl. Res. 35, 289 (2005).

    CAS  Google Scholar 

  24. 24

    S. Tajima, N. Nishimoto, Y. Kishi, S. Matsuya, and K. Ishikawa, Dent. Mater. J. 23, 329 (2004).

    Article  CAS  Google Scholar 

  25. 25

    M. Sivakumar and K. P. Rao, J. Biomed. Mater. Res., Part A 65A, 222 (2003).

    Article  CAS  Google Scholar 

  26. 26

    I. Lévêque, K. H. Rhodes, and S. Mann, J. Mater. Chem. 12, 2178 (2002).

    Article  Google Scholar 

  27. 27

    M. Takechi, Y. Miyamoto, K. Ishikawa, T. Toh, T. Yuasa, M. Nagayama, and K. Suzuki, Biomaterials 19, 2057 (1998).

    Article  CAS  Google Scholar 

  28. 28

    X. P. Wang, L. Chen, H. Xiang, and J. D. Ye, J. Biomed. Mater. Res., Part B: Appl. Biomater. 81B, 410 (2007).

    Article  CAS  Google Scholar 

  29. 29

    S. M. Kuo, S. J. Chang, T. W. Chen, and T. C. Kuan, J. Biomed. Mater. Res., Part A 76A, 408 (2006).

    Article  CAS  Google Scholar 

  30. 30

    T. Dvir, O. Tsurgang, and S. Cohen, Isr. J. Chem. 45, 487 (2005).

    Article  CAS  Google Scholar 

  31. 31

    Z. S. Li, H. R. Ramay, K. D. Hauch, D. M. Xiao, and M. Q. Zhang, Biomaterials 26, 3919 (2005).

    Article  CAS  Google Scholar 

  32. 32

    D. W. Hutmacher, J. C. H. Goh, and S. H. Teoh, Ann. Acad. Med. Singapore 30, 183 (2001).

    CAS  Google Scholar 

  33. 33

    S. Itoh, I. Yamaguchi, M. Suzuki, S. Ichinose, K. Takakuda, H. Kobayashi, K. Shinomiya, and J. Tanaka, Brain Res. 993, 111 (2003).

    Article  CAS  Google Scholar 

  34. 34

    H. Milhofer-Furedi, P. Bar Yosef Ofir, M. Sikirin, C. Gergely, and F. Cuisinier, WO Patent No. 2004047880 (10 June 2004).

  35. 35

    D. M. Price, M. Reading, and T. J. Lever, J. Therm Anal. Calorim. 56, 673 (1999).

    Article  CAS  Google Scholar 

  36. 36

    J. R. Adams and N. M. Bashara, Surf. Sci. 47, 655 (1975).

    Article  CAS  Google Scholar 

  37. 37

    J. Vörös, Biophys. J. 87, 553 (2004).

    Article  Google Scholar 

  38. 38

    LEAD Technologies, SPPS@Base system, LEAD Technologies Inc., 2002.

  39. 39

    SPSS, Regression, 2004.

  40. 40

    J. Leckenby, D. Faddis, and G. Hsiao, Combined thermal, mechanical, and morphological characterization of polymers on a nanometer spatial scale. 1999 (cited 6 July 2004). Available from http://www.iscpubs.com/ articles/al/a9904lec.pdf

  41. 41

    H. M. Pollock and A. Hammiche, J. Phys. D: Appl. Phys. 34, R23 (2001).

    Article  Google Scholar 

  42. 42

    D. M. Price, M. Reading, A. Caswell, A. Hammiche, and H. M. Pollock, Microscopy and Analysis 65, 17 (1998).

    Google Scholar 

  43. 43

    P. Peng, Ph.D. thesis, University of South Australia, 2005.

  44. 44

    A. S. Posner, N. C. Blumenthal, and F. Betts, Chemistry and Structure of Precipitated Hydroxyapatites (Springer-Verlag, Berlin, Heidelberg, 1984), pp. P155-P171.

    Google Scholar 

  45. 45

    M. Shirkhanzadeh, J. Mater. Sci. Lett. 12, 16 (1993).

    CAS  Google Scholar 

  46. 46

    S. Rossler, A. Sewing, M. Stolzel, R. Born, D. Scharnweber, M. Dard, and H. Worch, J. Biomed. Mater. Res., Part B: Appl. Biomater 64, 655 (2002).

    Google Scholar 

  47. 47

    R. A. A. Muzzarelli, Natural Chelating Polymers (Pergamon, Oxford, 1937), p. 256.

    Google Scholar 

  48. 48

    S. Kim, Y. Kim, J. Jegal, G. Lim, and K. Lee, J. Appl. Polym. Sci. 85, 714 (2002).

    Article  CAS  Google Scholar 

  49. 49

    R. Valentin, R. Horga, B. Bonelli, E. Garrone, F.D. Renzo, and F. Quignard, Biomacromolecules 7, 877 (2006).

    Article  CAS  Google Scholar 

  50. 50

    R. Murugan and S. Ramakrishna, Biomaterials 25, 3829 (2004).

    Article  CAS  Google Scholar 

  51. 51

    X. Yan, E. Khor, and L. Lim, J. Biomed. Mater. Res., Part B: Appl. Biomater. 58, 358 (2001).

    Article  CAS  Google Scholar 

  52. 52

    X. Yan, E. Khor, and L. Lim, Chem. Pharm. Bull. (Tokyo) 48, 941 (2000).

    Article  CAS  Google Scholar 

  53. 53

    G. Lawrie, I. Keen, A. Chandler-Temple, B. Drew, P. Fredericks, and L. Grøndahl, Biomacromolecules 8, 2533 (2007).

    Article  CAS  Google Scholar 

  54. 54

    P. Costa and J. M. S. Lobo, Eur. J. Pharm. Sci. 13, 123 (2001).

    Article  CAS  Google Scholar 

  55. 55

    N. A. Peppas, Pharm. Acta Helv. 60, 110 (1985).

    CAS  Google Scholar 

  56. 56

    G. Willmann, Adv. Eng. Mater. 1, 95 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Peng, P., Voelcker, N.H., Kumar, S. et al. Concurrent elution of calcium phosphate and macromolecules from alginate/chitosan hydrogel coatings. Biointerphases 3, 105–116 (2008). https://doi.org/10.1116/1.3046123

Download citation