Skip to main content
Log in

Stability of alginate microbead properties in vitro

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

Abstract

Alginate microbeads have been investigated clinically for a number of therapeutic interventions, including drug delivery for treatment of ischemic tissues, cell delivery for tissue regeneration, and islet encapsulation as a therapy for type I diabetes. The physical properties of the microbeads play an important role in regulating cell behavior, protein release, and biological response following implantation. In this research alginate microbeads were synthesized, varying composition (mannuronic acid to guluronic acid ratio), concentration of alginate and needle gauge size. Following synthesis, the size, volume fraction, and morphometry of the beads were quantified. In addition, these properties were monitored over time in vitro in the presence of varying calcium levels in the microenvironment. The initial volume available for solute diffusion increased with alginate concentration and mannuronic (M) acid content, and bead diameter decreased with M content but increased with needle diameter. Interestingly, microbeads eroded completely in saline in less than 3 weeks regardless of synthesis conditions much faster than what has been observed in vivo. However, microbead stability was increased by the addition of calcium in the culture medium. Beads synthesized with low alginate concentration and high G content exhibited a more rapid change in physical properties even in the presence of calcium. These data suggest that temporal variations in the physical characteristics of alginate microbeads can occur in vitro depending on synthesis conditions and microbead environment. The results presented here will assist in optimizing the design of the materials for clinical application in drug delivery and cell therapy.

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. Opara EC, Mirmalek-Sani SH, Khanna O, Moya ML, Brey EM. Design of a bioartificial pancreas(+). J Investig Med. 2010;58(7):831–7. doi:10.231/JIM.0b013e3181ed3807.

    Google Scholar 

  2. Garfinkel, Harland RC, Opara EC. Optimization of the microencapsulated islet for transplantation. J Surg Res. 1998;76(1):7–10. doi:10.1006/jsre.1997.5258.

    Article  CAS  Google Scholar 

  3. Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials. 1999;20(1):45–53. doi:10.1016/S0142-9612(98)00107-0.

    Article  CAS  Google Scholar 

  4. Khanna O, Moya ML, Opara EC, Brey EM. Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1. J Biomed Mater Res A. 2010;95(2):632–40. doi:10.1002/jbm.a.32883.

    Google Scholar 

  5. Khanna O, Moya ML, Greisler HP, Opara EC, Brey EM. Multilayered microcapsules for the sustained-release of angiogenic proteins from encapsulated cells. Am J Surg. 2010;200(5):655–8. doi:10.1016/j.amjsurg.2010.08.001.

    Article  CAS  Google Scholar 

  6. Moya ML, Garfinkel, Liu X, Lucas S, Opara EC, Greisler HP, Brey EM. Fibroblast growth factor-1 (FGF-1) loaded microbeads enhance local capillary neovascularization. J Surg Res. 2010;160(2):208–12. doi:10.1016/j.jss.2009.06.003.

    Article  CAS  Google Scholar 

  7. Maguire TJ, Novik EI, Schloss R, Yarmush ML Alginate encapsulation and hepatic differentiation of embryonic stem cells. In: Bioengineering conference, 2005. Proceedings of the IEEE 31st Annual Northeast, 2–3 April 2005. pp 213–214.

  8. Moya ML, Cheng MH, Huang JJ, Francis-Sedlak ME, Kao SW, Opara EC, Brey EM. The effect of FGF-1 loaded alginate microbeads on neovascularization and adipogenesis in a vascular pedicle model of adipose tissue engineering. Biomaterials. 2010;31(10):2816–26. doi:10.1016/j.biomaterials.2009.12.053.

    Article  CAS  Google Scholar 

  9. Moya ML, Lucas S, Francis-Sedlak M, Liu X, Garfinkel, Huang JJ, Cheng MH, Opara EC, Brey EM. Sustained delivery of FGF-1 increases vascular density in comparison to bolus administration. Microvasc Res. 2009;78(2):142–7. doi:10.1016/j.mvr.2009.06.006.

    Article  CAS  Google Scholar 

  10. Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2002;54(1):3–12. doi:10.1016/S0169-409X(01)00239-3.

    Article  CAS  Google Scholar 

  11. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101(7):1869–79. doi:10.1055/s-2007-973087.

    Article  CAS  Google Scholar 

  12. Amsden B. Solute diffusion in hydrogels.: an examination of the retardation effect. Polym Gels Netw. 1998;6(1):13–43. doi:10.1016/S0966-7822(97)00012-9.

    Article  CAS  Google Scholar 

  13. Goosen MFA. Physico-chemical and mass transfer considerations in microencapsulation. Ann NY Acad Sci. 1999;875(1):84–104. doi:10.1111/j.1749-6632.1999.tb08496.x.

    Article  CAS  Google Scholar 

  14. Uludag H, De Vos P, Tresco PA. Technology of mammalian cell encapsulation. Adv Drug Deliv Rev. 2000;42(1-2):29–64. doi:10.1016/S0169-409X(00)00053-3.

    Article  CAS  Google Scholar 

  15. Wee S, Gombotz WR. Protein release from alginate matrices. Adv Drug Deliv Rev. 1998;31(3):267–85. doi:10.1016/S0169-409X(97)00124-5.

    Article  Google Scholar 

  16. Ruel M, Laham RJ, Parker JA, Post MJ, Ware JA, Simons M, Sellke FW. Long-term effects of surgical angiogenic therapy with fibroblast growth factor 2 protein. J Thorac Cardiovasc Surg. 2002;124(1):28–34. doi:10.1067/mtc.2002.121974.

    Article  CAS  Google Scholar 

  17. Sellke FW, Laham RJ, Edelman ER, Pearlman JD, Simons M. Therapeutic angiogenesis with basic fibroblast growth factor: technique and early results. Ann Thorac Surg. 1998;65(6):1540–4. doi:10.1016/S0003-4975(98)00340-3.

    Article  CAS  Google Scholar 

  18. Khurana R, Simons M. Insights from angiogenesis trials using fibroblast growth factor for advanced arteriosclerotic disease. Trends Cardiovasc Med. 2003;13(3):116–22. doi:10.1016/S1050-1738(02)00259-1.

    Article  CAS  Google Scholar 

  19. Vacanti CA, Bonassar LJ, Vacanti MP, Shufflebarger J. Replacement of an avulsed phalanx with tissue-engineered bone. N Engl J Med. 2001;344(20):1511–4. doi:10.1056/NEJM200105173442004.

    Article  CAS  Google Scholar 

  20. Cook WH, Smith DB. Molecular weight and hydrodynamic properties of sodium alginate. Can J Biochem Physiol. 1954;32(3):227–39.

    Article  CAS  Google Scholar 

  21. Amsden B. Solute diffusion within hydrogels. Mechanisms and models. Macromolecules. 1998;31(23):8382–95. doi:10.1021/ma980765f.

    Article  CAS  Google Scholar 

  22. Hobbs HA, Kendall WFJ, Darrabie M, Opara EC. Prevention of morphological changes in alginate microcapsules for islet xenotransplantation. J Investig Med. 2001;49(6):572–5. doi:10.2310/6650.2001.33722.

    Article  CAS  Google Scholar 

  23. Martinsen A, Skjåk-Bræk G, Smidsrød O. Alginate as immobilization material: i. correlation between chemical and physical properties of alginate gel beads. Biotechnol Bioeng. 1989;33(1):79–89. doi:10.1002/bit.260330111.

    Article  CAS  Google Scholar 

  24. Bajpai SK, Sharma S. Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ions. React Funct Polym. 2004;59(2):129–40. doi:10.1016/j.reactfunctpolym.2004.01.002.

    Article  CAS  Google Scholar 

  25. Amsden B, Turner N. Diffusion characteristics of calcium alginate gels. Biotechnol Bioeng. 1999;65(5):605–10. doi:10.1002/(SICI)1097-0290(19991205)65:5<605:AID-BIT14>3.0.CO;2-C[pii].

    Article  CAS  Google Scholar 

  26. Darrabie MD, Kendall WF, Opara EC. Effect of alginate composition and gelling cation on microbead swelling. J Microencapsul. 2006;23(6):613–21. doi:10.1080/02652040600687621.

    Article  CAS  Google Scholar 

  27. Klokk TI, Melvik JE. Controlling the size of alginate gel beads by use of a high electrostatic potential. J Microencapsul. 2002;19(4):415–24. doi:10.1080/02652040210144234.

    Article  CAS  Google Scholar 

  28. Yamagiwa K, Kozawa T, Ohkawa A. Effects of alginate composition and gelling conditions on diffusional and mechanical properties of calcium-alginate gel beads. J. Chem. Eng. 1995;28:462–7. doi:10.1252/jcej.28.462.

    Article  CAS  Google Scholar 

  29. Kendall WF, Jr, Darrabie MD, El-Shewy HM, Opara EC. Effect of alginate composition and purity on alginate microspheres. J Microencapsul. 2004;21(8):821–8. doi:10.1080/02652040400015452.

    Article  CAS  Google Scholar 

  30. Gu F, Amsden B, Neufeld R. Sustained delivery of vascular endothelial growth factor with alginate beads. J Control Release. 2004;96(3):463–72. doi:10.1016/j.jconrel.2004.02.021S0168365904000999[pii].

    Article  CAS  Google Scholar 

  31. Edelman ER, Mathiowitz E, Langer R, Klagsbrun M. Controlled and modulated release of basic fibroblast growth factor. Biomaterials. 1991;12(7):619–26. doi:10.1016/0142-9612(91)90107-L.

    Article  CAS  Google Scholar 

  32. Dowd CJ, Cooney CL, Nugent MA. Heparan Sulfate Mediates bFGF Transport through Basement Membrane by Diffusion with Rapid Reversible Binding. J. Biol. Chem. 1999;274:5236–5244. doi:10.1074/jbc.274.8.5236.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported, in part, by funding from the Gates Foundation (MLM), Mr. Edward Ross (MM, OK), Department of Veterans Affairs (EMB), National Science Foundation (Grant Nos: 0852048 and 0731201) and National Institutes of Health (Grant No: RO1 DK080897).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eric M. Brey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moya, M.L., Morley, M., Khanna, O. et al. Stability of alginate microbead properties in vitro. J Mater Sci: Mater Med 23, 903–912 (2012). https://doi.org/10.1007/s10856-012-4575-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4575-9

Keywords

Navigation