Advanced Biomaterials and Devices in Medicine
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Advanced Biomaterials and Devices in Medicine
December 2014, Volume 1, Issue 1, pp 1-10

Poly(lactic acid) microspheres for local delivery of bioinorganics for applications in bone regeneration

Z. Tahmasebi Birgani1, B.J. Klotz1, 2, C.A. van Blitterswijk1, 3, P. Habibovic1, 3*

1 Department of Tissue Regeneration, University of Twente, Enschede, 7500 AE, The Netherlands
2 Department of Oral and Maxillofacial Surgery and Special Dental Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
3 MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6200 MD, The Netherlands

* Corresponding author: Prof. Pamela Habibovic, e-mail:

Bioinorganics are a family of relatively simple and inexpensive inorganic compounds, which, although often present only in trace amounts, are known to play an important role in the normal functioning of organs and tissues, including bone. Bioinorganics can potentially be used for improving the clinical performance of synthetic bone graft substitutes, as an alternative to growth factors and other biologics. To this end, it is imperative to fully understand their mechanism of action. Currently, bioinorganics are usually incorporated into calcium phosphate and bioglasses. During degradation, these materials release a cocktail of ions, making the study of the effect of the bioinorganic of interest difficult, if not impossible. To overcome this issue, in the present study we attempted to develop a delivery system for bioinorganics based on polymeric microspheres. Calcium chloride, as a model for bioinorganics, was incorporated into poly(lactic acid) microspheres, using a single emulsion-solvent evaporation technique. These microspheres were used to study the effect of the released calcium ions on the proliferation and osteogenic differentiation of human mesenchymal stromal cells in a trans-well culture system. The results showed that it was possible to incorporate calcium into the microspheres and that the efficiency of incorporation could be increased by increasing the initial amount of poly(lactic acid), and by using sonication instead of mechanical force during the emulsification step. Furthermore, the release profile of calcium from the microspheres was also dependent on the emulsification method. Cell culture experiments revealed no effect on cell proliferation or alkaline phosphatase activity as a consequence of calcium release, however, the gene expression of bone morphogenetic protein 2 and osteopontin was increased when cells were cultured in the presence of calcium containing microspheres. In conclusion, this study demonstrates that it is possible to use the developed polymeric delivery system to study the specific chemical effects of bioinorganics on the cells behavior.

Keywords: bioinorganics, poly(lactic acid) microspheres, calcium release, single emulsion-solvent evaporation technique, osteogenic differentiation

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